news about Im­mu­ni­ty­Bio and In­ven­ti­va: Uni­ty Biotech­nol­o­gy shelves work: The an­ti-ag­ing drug de­vel­op­er plans to eval­u­ate strate­gic al­ter­na­tives and con­duct … Get free access to a limited number of articles plus choose newsletters to get straight to your inbox Enter the email associated to with your Endpoints account and we'll send you a one-time login link (no password needed) and we'll send you a link to reset your password The link expires after 24 hours and can only be used once Sign up for free to read a limited number of articles each month Pick what newsletters get delivered to your inbox each week Want unlimited access? Sign up for a premium subscription plan would allow law enforcement to determine if drivers are operating a vehicle while impaired through oral fluid screenings State Representative Brian Begole believes there's been a decrease in drivers operating under the influence of alcohol but says Michigan needs to do more to address drivers operating under the influence of drugs "I think if people knew how many people were out there operating under the influence of narcotics The proposed testing would use a handheld instrument with a mouth swab to enable officers to complete real-time testing to determine whether a driver has drugs in their system it'll tell you if the subject is under the influence of methamphetamine cannabis or THC and benzodiazepine," Begole said Michigan initiated pilot programs in 2016 that permitted roadside oral fluid screenings more than 20 states have oral fluid authorization written into law with many modeling their legislation after Michigan's approach "The National Transportation Safety Board has recommended that Michigan adopt these practices of the oral fluid testing on the roadside to improve the safety on our streets," Begole said The oral fluid screening would be conducted after field sobriety tests and preliminary breath testing if there is probable cause for a drug-impaired arrest The test involves placing a sterile swab in the mouth and rubbing it under the gums and tongue The sample is then analyzed by a handheld screening machine within five minutes Data from the pilot programs showed the technology was easy to use reliable and accurate for preliminary roadside testing The National Transportation Safety Board (NTSB) recommends making this type of testing permanent, especially considering that over 10,000 crashes involving an impaired driver occurred in 2023, according to Michigan State Police nearly 2,500 people in Michigan have died due to drug-involved crashes in the last decade "Statistics show that driving under the influence of narcotic has increased about 22% over the last several years," Begole adds Begole is hopeful oral fluid screenings will offer drivers more safety on the streets "I'm optimistic that this is something that we can get through the House and right onto the governor's desk," Begole said The bill has been referred to the House Government Operations Committee for consideration This story was reported by a journalist and has been converted to this platform with the assistance of AI Our editorial team verifies all reporting on all platforms for fairness and accuracy Follow FOX 17: Facebook - X (formerly Twitter) - Instagram - YouTube but we just felt in our plums that we had to cover the greatest outtake ever filmedBy • -The two funniest television scenes of the 21st century never actually aired Late in the first season of Eastbound & Down there’s a showdown between washed-up major league reliever Kenny Powers (Danny McBride) and his former rival Reg Mackworthy (Craig Robinson) But before they square off on a makeshift baseball diamond in a parking lot Ric Flair–haired BMW dealer Ashley Schaeffer (Will Ferrell) King of Fools: The Oral History of Danny McBride Schaeffer’s shit stirring doesn’t last very long he did whatever he possibly could to make McBride and Robinson laugh The results—the outtakes—are now the stuff of legend Watching them is like taking hits of nitrous.During the first exchange Schaeffer says that he can feel the tension in his “plums.” During the second when McBride and Robinson are standing nose to nose Schaeffer tells a story about his “young son Gabriel” walking in on him and his wife having sex The moment might be the quintessential example of the long-gone let-the-cameras-roll-and-see-what-happens era of comedy stars like Ferrell were encouraged to just try shit Stephanie Laing (co–executive producer): I’m fairly certain it was the first season where I was like we’ve rolled 12,000 feet of film.” They were improvising the end of the scene “Cut.” I’d just never seen anything like it and you don’t want to leave.David Gordon Green (consulting producer): The fact that we had Will Ferrell behind the show When other people were looking at us cross-eyed and confused Will put his face on the show and really took a risk.Danny McBride (cocreator and star): There’s just something about Will that inherently is so funny.Jody Hill (cocreator): Will Ferrell at the time was such a big star it was a thrill for everybody that he was actually going to be in the show it was like everybody was just giddy.Steve Little (Stevie Janowski): When you’re an actor and this will lead me somewhere.” I remember that scene at the car dealership maybe everything led here.”Laing: I don’t even think we had that much time to shoot it but we were definitely at the end of a long day it was a blur because it was so good.McBride: That was all just part of a jam-packed 10-hour day But we were just going balls to the wall and just having a blast with it.Green: And to see those three comedic champions not be able to keep a straight face we should be so lucky in our lives to be able to witness that “What are we watching right now?”Katy Mixon Greer (April Buchanon): Will Ferrell is hysterical “My plums,” there’s no words to describe it.Craig Robinson (Reg Mackworthy): That line was one of his bombs Will Ferrell (Ashley Schaeffer, in 2012): Ashley Schaeffer is one of the crazier characters I’ve done by far There’s a point where my wife was watching with me “That might be the most disgusting person you’ve ever played,” and it just made me laugh.McBride: And when you have to be in a scene with him and you look him in the eyes it is pretty much impossible to remain calm.Robinson: You have to stare Danny McBride in the eye while Will Ferrell is improvising He’s just trying to kill you.McBride: You can see the gears spinning And then without putting any more effort into it he can just double down on that and just keep drilling in and drilling in and drilling in until you’re unwound The Righteous Bros: In Praise of the Danny McBride Multiverse Did ‘Eastbound & Down’ Stick the Landing McBride: The pure joy of being in a scene with those two guys and making something that is legitimately making people want to piss their pants and being in the middle of it and trying to not be the one who ruins it.Mixon Greer: That was a very, very epic day. Green: It’s three people that don’t break, breaking. It’s just a kid in a candy store watching that type of joy. Like when you’re 12 years old and you fart in church and you think you’re going to get in trouble—the more that you keep giggling, the more you feel like you’re striking some sort of comedy gold. You’re going to be able to open the treasure chest with your friends and keep this thing going. ArchiveWe’ve been around since Brady was a QB Food and Drug Administration (FDA) accepted its New Drug Application (NDA) submission for an investigational once-daily 25 mg oral formulation of Wegovy® (semaglutide) for chronic weight management in adults living with obesity or overweight with one or more comorbid conditions and to reduce the risk of major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease.2 If approved Wegovy® would become the first oral formulation of a GLP-1 indicated for chronic weight management "We are entering a new era of obesity care where patients want individualized treatment plans that address their needs and provide choices including oral formulations," said Anna Windle Medical & Regulatory Affairs at Novo Nordisk Inc "Novo Nordisk's strong legacy in obesity care and decades of scientific research and innovation have brought us to this moment We are pleased that the FDA has accepted our submission and look forward to working with regulatory authorities on what would be the first oral GLP-1 treatment for obesity." The FDA application is based on results from OASIS 4 controlled trial evaluating the efficacy and safety of once-daily oral semaglutide 25 mg versus placebo in 307 adults with obesity (BMI >/= 30 kg/m2) or overweight (BMI >/= 27 kg/m2) with one or more comorbidities.1,3 Patients with diabetes were excluded.1,3 OASIS 4 included a 64-week treatment period including a 12-week dose escalation and a 7-week off-treatment follow-up period.1,3 In total 307 participants were randomized 2:1 ratio to once-daily oral semaglutide 25 mg or placebo as an adjunct to lifestyle intervention for 64 weeks.1,3 The FDA action date to decide on the Wegovy® oral formulation NDA will be in Q4 2025.2 About Wegovy®Wegovy® (semaglutide) injection 2.4 mg is currently approved along with a reduced calorie diet and increased physical activity for adults and children aged 12 years and older with obesity or some adults with overweight who also have weight-related medical problems to help them lose excess body weight and keep the weight off and to reduce the risk of major cardiovascular events such as death or stroke in adults with known heart disease and either obesity or overweight.4 and misunderstood disease that requires long-term management.5-7 One key misunderstanding is that this is a disease of just lack of willpower when in fact there is underlying biology that may impede people with obesity from losing weight and keeping it off.5,7 Obesity is influenced by a variety of factors The prevalence of overweight and obesity is a public health issue that has severe cost implications to healthcare systems.10,11 In the U.S. Liz Skrbkova (US)+1 609 917 0632[email protected] Ambre James-Brown (Global)+45 3079 9289[email protected] +1 609 613 0568[email protected] Jacob Martin Wiborg Rode (Global)+45 3075 5956[email protected] +45 3079 6656 [email protected] +45 3077 5649 [email protected] Max Ung (Global)+45 3077 6414mxun@novonordisk.com © 2025 Novo Nordisk     All rights reserved.     US25SEMO00927     May 2025 the country's largest Pharmacy Benefit Manager (PBM) has decided that Wegovy® (semaglutide).. The New England Journal of Medicine (NEJM) published results from part 1 of the ongoing phase 3 ESSENCE trial which investigated the effects.. Health Care & Hospitals Medical Pharmaceuticals Pharmaceuticals Clinical Trials & Medical Discoveries Do not sell or share my personal information: Sign In Register THUNDER BAY — "This is quite an honour," said Bruce Pynn one of three University of Toronto graduates to receive Alumni of Influence awards this year U of T's faculty of dentistry describes the recipients as having sky-high goals being technically precise and impressively innovative and demonstrating a deep level of care for their patients.  Pynn is chief of dentistry/oral and maxillofacial surgery at Thunder Bay Regional Health Sciences Centre while also running a private practice and teaching at the Northern Ontario School of Medicine.  An online article posted by the U of T outlines a host of accomplishments and contributions and credits him with building "a meaningful career in a community where the needs are palpable," but adds that he remains modest about his work "I came to Thunder Bay from Toronto 30 years ago I'm super glad that I stayed," he says Pynn said he was a little older as a graduate from the U of T because he focused on research in a plastic surgery lab for years before going into dentistry "I came to Thunder Bay for a year to just make some money the oral surgeon.  We were kindred spirits He said the most rewarding aspect of his job is "fixing up" trauma patients "There's up to 10 fractured jaws per week so it's among the busiest services in the province for the fewest number of oral surgeons.  There are 200-plus in the province and only three up here looking after an area the size of France." Pynn said he's received requests to care for patients from as far away as Timmins He called the award "very special" because he puts a lot of effort into treating his patients and sometimes even goes to their homes to do a consultation or post-operative check "That's following in the footsteps of Dr because the next place for big oral surgery in Ontario is Toronto so I take the effort to see people and spend time with people." Pynn also supervises dental students at Confederation College and travels to Toronto monthly to oversee U of T oral surgery students he will take a long flight overseas to deliver a talk about his professional experiences in Thunder Bay at a meeting of the International Association of Oral and Maxillofacial Surgeons in Singapore This story was made possible by our Community Leaders Program partner Thank you to Waste Connections of Canada for helping to expand local news coverage in Thunder Bay. Learn more Patients with food allergy who discontinued oral immunotherapy were those who were more likely to experience a reaction to the treatment than those who reached maintenance of allergen foods, according to research at the Pediatric Academic Societies 2025 Meeting.  They were also more likely to experience moderate and severe reactions of the MD program at Weill Cornell Medical College in New York City “Oral immunotherapy discontinuation was low overall but varied by allergen with higher discontinuation rates observed for allergens with a high incidence of severe reactions compared to the mean,” they reported Food allergy affects an estimated 8% of children and 10% of adults in the United States but advances in oral immunotherapy have opened up treatment options for these individuals “The fear of adverse reactions remains a barrier to treatment yet little data exists on the role of adverse reactions in treatment discontinuation,” they wrote “Identifying factors associated with oral immunotherapy discontinuation is critical to addressing concerns and improving the safety and efficacy of oral immunotherapy.”  The researchers conducted a retrospective cohort study with data from 1003 patients who underwent oral immunotherapy for peanut and/or sesame allergy at Latitude Food Allergy Care between 2018 and 2024 They assessed all treatment-related reactions in terms of frequency They excluded patients lost to follow-up or updosing and stratified the remaining patients by those who discontinued treatment vs those who reached maintenance for all foods Those who discontinued treatment included 8.2% receiving oral immunotherapy for milk (Some patients were receiving oral immunotherapy for multiple allergens so there is overlap by allergen discontinuation rates.)  results revealed that patients undergoing oral immunotherapy for milk had more than twice the odds of discontinuing treatment (OR The average incidence of severe reactions was 13% About 1 in 5 patients (20%) who discontinued therapy had any reaction compared with 5.2% overall and 4.0% of those who reached maintenance “Patients who discontinued oral immunotherapy had similar frequencies of experiencing mild reactions compared to those who reached maintenance but a higher incidence of moderate and severe reactions,” the researchers reported Those who discontinued treatment also “had a higher frequency of reactions to oral immunotherapy doses including higher frequency of the top three reported symptoms of reaction: Mild abdominal pain and pruritus compared to the overall mean of those who reached maintenance.” Mild abdominal pain was reported in 5.5% of those who discontinued compared with 1.3% overall and 0.9% of those who reached maintenance Vomiting or diarrhea occurred in 4.5% of those who discontinued treatment compared with 0.4% overall and 0.3% who reached maintenance Pruritus occurred in 4.9% of those who discontinued compared with 2.1% overall and 1.9% of those who reached maintenance.  “The number of patients is very impressive and adds to the strengths of this retrospective study,” Jonathan Tam medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles He also noted that the rate of patients who discontinued oral immunotherapy overall was lower than published rates in clinical trials but the rate of severe reactions was conversely higher the discontinuation rate was generally low,” Tam said the findings make sense and are a practical guide to helping patients make decisions oral immunotherapy.”  The authors did not report receiving external funding or having any disclosures Tam was not involved with the study but is working with Latitude in a Children’s Hospital of Los Angeles clinic.  Tara Haelle is a science/health journalist based in Dallas Send comments and news tips to news@medscape.net Metrics details Emerging evidence links oral-derived gut microbes to colorectal cancer (CRC) development but CRC prognosis-related microbial alterations in oral remain underexplored In a retrospective study of 312 CRC patients we examined the oral microbiota using 16S rRNA gene full-length amplicon sequencing to identify prognostic microbial biomarkers for CRC Neisseria oralis and Campylobacter gracilis increased CRC progression risk (HR = 2.63 with P = 0.007 while Treponema medium showed protective effects (HR = 0.41 A microbial risk score (MRS) incorporating these species effectively predicted CRC progression risk (C-index = 0.68 When compared to a model constructed solely from clinical factors the predictive accuracy significantly improved with the addition of the MRS resulting in a C-index rising to 0.77 (P = 2.33 × 10−5) Our findings suggest that oral microbiota biomarkers may contribute to personalized CRC monitoring strategies their implementation in clinical surveillance necessitates confirmatory studies While the role of oral-derived microbes in CRC development is identified the mechanisms by which alterations in the oral microbiota are associated with CRC prognosis remain largely unknown These findings underscore the critical role of the oral microbiota in influencing cancer prognosis and further investigation of the prognostic function of oral microbiota in CRC is warranted we investigated the salivary microbiota of 312 CRC patients using 16S rRNA gene full-length sequencing We identified microbial signatures associated with CRC outcomes and developed a microbial risk score (MRS) to predict CRC progression we integrated the MRS with key clinical factors to construct a multi-factorial prognostic model with enhanced predictive performance While these findings require validation in multi-center cohorts our study pioneers the application of salivary microbiota profiling as a non-invasive prognostic tool in CRC Step 1: Saliva samples were collected from 312 CRC patients scheduled for surgical tumor resection The median follow-up time was 21.5 months for patients with disease progression and 25.4 months for survival Salivary microbiota profiling was performed using 16S rRNA full-length sequencing Step 2: Species-level identification was conducted with inclusion criteria of prevalence ≥10% and relative abundance ≥0.01% A 1:1 cross-validation strategy was applied by randomly splitting the cohort into discovery (n = 156) and test (n = 156) sets Prognosis-related microbes were identified using univariate and multivariate Cox regression analyses and Treponema medium as significant biomarkers Step 3: A microbial risk score (MRS) was constructed based on the identified prognostic bacterial species Clinical prognostic factors were also evaluated and a comprehensive model integrating microbiota biomarkers (three species) and clinical factors (three variables) was developed The performance of the comprehensive model was validated and compared with models based solely on the clinical factors demonstrating superior prognostic accuracy A Kaplan–Meier curve illustrating PFS stratified by the detection status of identified oral bacterial species P values were calculated using the log-rank test Numbers below each graph indicate the number of patients at risk at different time points B Volcano plot showing the hazard ratio (HR) and statistical significance of candidate prognostic bacterial species while the y axis shows −log10-transformed false discovery rates (FDR) Circle size indicates the frequency of significance in 1000 cross-validation tests using univariate Cox regression and color intensity (gray to red) represents the frequency of significance in multivariate Cox regression analysis The multivariate Cox regression model was adjusted for age A Comparison of the predictive performance (C-index) of all combinations of microbial risk scores derived from the three identified prognostic species in the test datasets using the Cox regression model B Kaplan–Meier curves for PFS stratified by microbial risk scores (MRS) into low (n = 38) Numbers below the graph indicate patients at risk at different time points The P value is calculated by the log-rank test C Kaplan–Meier curves for overall survival stratified by the MRS D Comparison of the predictive performance (C-index) of all combinations of clinical factors (perineural invasion and tumor stage) in the test datasets using the Cox regression model E Performance comparison of the clinical model and comprehensive model (integrating both clinical and microbial factors) in the test datasets using the Cox regression model The P value for the comparison between the clinical model and the comprehensive model was calculated using a Z score test The bars represent the 95% confidence intervals calculated by the bootstrap method F Performance comparison of the clinical model and comprehensive model in the test datasets using the random survival forest (Rsf) method The bars represent the 95% confidence intervals calculated by bootstrap method only 4 out of 38 patients exhibited progression (10.5%) compared to 20 out of 150 patients in the MRS-Moderate group (13.3%) and 35 out of 124 patients in the MRS-High group (28.2%) experienced disease progression post-surgery A Heatmap of Spearman correlation between prognostic species and differential pathways The KEGG pathways were predicted using PICRUSt2 to infer the functional shifts in the microbiota of MRS-Low and MRS-moderate/high patients The strength of the color depicted Spearman’s correlation coefficients (negative correlation B The differential analysis of the oral microbial community’s functions between MRS-moderate/high and MRS-low groups The analysis focused on KEGG pathways with an average relative abundance exceeding 1% and the P value is corrected using the Bonferroni method The difference in mean proportion for pathways showing significant differences in abundance was shown The 95% confidence intervals and statistical significance (P value corrected) were indicated as well Evidence of oral microbiota as prognostic indicators for CRC remains limited we identified three oral bacteria associated with CRC prognosis based on follow-up data from patients and constructed an oral MRS for predicting CRC prognosis This approach enables the qualitative detection of the target species through a simple and straightforward PCR method potentially providing advantages for monitoring the postoperative progression risk for CRC patients These multilayered interactions underscore the importance of oral microbiota balance in the development of CRC These findings elucidate the mechanistic roles of these oral pathobionts in mediating unfavorable CRC prognosis through oral-gut axis translocation medium is associated with a reduced risk of CRC progression medium may contribute to reducing CRC progression risk warrant further exploration in future studies These pathogen–host interactions are involved in the carcinogenesis of CRC we did not observe the significant associations between these microbes and CRC progression which can partly be explained by the fact that the molecular events driving carcinogenesis and the biological processes driving disease progression (e.g. therapeutic resistance) frequently involve distinct biological mechanisms Our current prognostic analyses are confined to CRC patient cohorts where oral microbial profiles inherently exhibit baseline homogeneity due to their shared carcinogenesis-associated signatures bacterial taxa already enriched in CRC populations (e.g. F.nucleatum) may demonstrate attenuated prognostic discriminative power this study primarily utilized a single-center design and lacks an external validation cohort which restricts the generalizability of our predictive model necessitating future validation through multi-center studies with independent cohorts we conducted a series of sensitivity analyses to ensure the robustness of our results including randomization of the sample division and different model-constructed approaches the relatively small number of progression events (n = 59) may affect the statistical power of our findings Future prospective investigations incorporating multi-center designs and extended follow-up periods are required to reliably identify CRC prognostic biomarkers while our analysis suggests potential microbial metabolic pathway involvement the proposed associations between identified microbes and clinical outcomes require experimental validation through in vitro and in vivo studies to elucidate the mechanisms underlying the influence of oral microbiota on CRC progression we acknowledge several methodological constraints of this study while implementing enhanced mechanical lysis quantitative assessment of microbial lysis efficiency was not conducted leaving potential Gram-positive bacterial under-lysis unverified the inherent primer bias of 16S rRNA sequencing may skew microbial composition which has the potential to be biased towards amplifying specific bacteria As a high percentage of host genomic DNA is present in oral specimens 16S rRNA sequencing is widely used in oral microbiota research due to its cost-effectiveness while metagenomic sequencing data are necessary for more precise information on taxonomic composition inferred metabolic pathways through PICRUSt2 disregard strain-level heterogeneity Future studies should integrate shotgun metagenomics with metabolomic profiling to establish host-microbiota interactions our study suggests potential associations between N medium with the risk of postoperative progression in CRC By integrating clinical and microbial factors we achieved improved predictive accuracy for progression risk compared to clinical factors alone These findings collectively provide preliminary evidence for exploring oral microbiota-based biomarkers for CRC progression the implementation of oral microbial indicators in CRC clinical surveillance required future confirmatory studies All patients were collected the clinical information the saliva samples were collected from patients who were instructed to refrain from eating and drinking for at least 30 min before the collection process The participants were guided to open the collection tubes and let saliva flow into them effortlessly which was collected using sterile 50 ml centrifuge tubes The collected saliva was temporarily stored in an ice box and transferred to 2 ml centrifuge tubes within two hours and subsequently stored at −80 °C for long-term preservation DNA extracted from each salivary sample served as the template for amplifying the full-length region of the 16S rRNA gene We amplified the full-length 16S rRNA gene using universal primers 27 F (5’-AGR GTT YGA TYM TGG CTC AG-3’) and 1492 R (5’-RGY TAC CTT GTT ACG ACT T-3’) Saliva-derived DNA was amplified using KAPA HiFi HotStart DNA Polymerase (KAPA Biosystems) for 27 cycles The process involved denaturation at 95 °C for 30 s We used Agencourt AMPure XP (Beckman Coulter) for fragment selection and purification of the PCR products We prepared the SMRTbell libraries from the purified amplicons by ligating adapters and sequenced them using the PacBio Sequel platform (Pacific Biosciences) We obtained high-quality circular consensus sequence (CCS) reads from the raw PacBio sequencing data using SMRT Link software (v9.0.0 Pacific Biosciences) and assigned multiplexed libraries to each sample using Lima (v2.0.0) based on the barcodes All statistical analyses and visualization procedures were performed using R software (version 4.4.0) with designated R packages A total of 291 bacterial species were observed of which 98 were included in the prognosis analysis which met criteria with a frequency exceeding 10% in the total sample and a relative abundance >0.01% Patients were divided into two groups based on the median abundance of each species and a univariate Cox regression model was performed Species that were statistically significant were subsequently incorporated into a multivariate Cox regression model we applied Monte Carlo simulation cross-validation for a robust selection by randomly partitioning the entire datasets into discovery and validation sets (1:1) and performing 1000 times randomized resampling we performed univariate and multivariate Cox regression models to identify the species associated with prognosis (P < 0.05) Species with significance in the discovery stage were then included in the validation set for confirmation three bacterial species were identified as prognostic biomarkers demonstrating substantial effect sizes (HR > 1.5 or HR < 0.8) and significance (corrected FDR < 0.1) Three validated oral bacterial species significantly associated with CRC prognosis were included to construct an MRS which was conversely associated with good prognosis The presence of species indicating poor prognosis or the absence of species indicating good prognosis was scored as one point each Each patient was assigned an MRS ranging from 0 to 3 To evaluate the performance of the combinations 50% of the samples (156 out of 312) were randomly selected 1000 times without replacement to create a pool of test datasets and the concordance index (C-index) across the test datasets was used as an indicator of model stability was categorized by assigning scores 0 for MRS low to comprehensively predict the probability of PFS in CRC patients We constructed a clinical model based on selected clinical factors all of which were statistically significant in a univariate Log-rank test A comprehensive model was constructed by integrating both clinical factors and MRS We calculated the concordance index (C-index) to evaluate the performance of the models and compared the differences in predictive performance between models incorporating and excluding MRS we utilized STAMP software to evaluate significant differential metabolic pathways between moderate/high and low MRS groups applying the Bonferroni correction with adjusted p value < 0.05 considered significant The correlation between oral microbes and the significantly related differential pathways was performed by Spearman’s rank correlation test along with the corresponding patient metadata are currently being uploaded to the China National Center for Bioinformation (CNCB) Full access to these resources will be public prior to the publication of the study The key computer codes for the analyses in this study are available on https://github.com/ZSH-AMF/Key_code.git Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries Predicting prognosis in colorectal cancer patients with curative resection using albumin The association of oral microbiome dysbiosis with gastrointestinal cancers and its diagnostic efficacy Characteristics of the salivary microbiota in patients with various digestive tract cancers The oral microbiota in colorectal cancer is distinctive and predictive Colorectal cancer patients have four specific bacterial species in oral and gut microbiota in common-a metagenomic comparison with healthy subjects Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project The Gum-gut axis: periodontitis and the risk of gastrointestinal cancers Oral-gut bacterial profiles discriminate between periodontal health and diseases Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 Inflammasome Analysis of salivary mycobiome in a cohort of oral squamous cell carcinoma patients from sudan identifies higher salivary carriage of malassezia as an independent and favorable predictor of overall survival Influence of pre-treatment saliva microbial diversity and composition on nasopharyngeal carcinoma prognosis Fusobacterium nucleatum induces a tumor microenvironment with diminished adaptive immunity against colorectal cancers Clinicopathological features of stage I-III colorectal cancer recurrence over 5 years after radical surgery without receiving neoadjuvant therapy: evidence from a large sample study Colorectal cancer recurrence and its impact on survival after curative surgery: An analysis based on multistate models Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status Tumour-associated and non-tumour-associated microbiota: addendum The impact of the gut microbiota on prognosis after surgery for colorectal cancer - a systematic review and meta-analysis Oral microbiota as novel biomarkers for colorectal cancer screening Saliva as diagnostic material and current methods of collection from oral cavity Enterotypical Prevotella and three novel bacterial biomarkers in preoperative stool predict the clinical outcome of colorectal cancer Oncomicrobial community profiling identifies clinicomolecular and prognostic subtypes of colorectal cancer Periodontal disease and cancer risk: a nationwide population-based cohort study tooth loss and colorectal cancer risk: results from the Nurses’ health study Human oral microbiome dysbiosis as a novel non-invasive biomarker in detection of colorectal cancer Global investigations of fusobacterium nucleatum in human colorectal cancer Oral microbiota as promising diagnostic biomarkers for gastrointestinal cancer: a systematic review Extensive transmission of microbes along the gastrointestinal tract Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models Association between bacteremia from specific microbes and subsequent diagnosis of colorectal cancer The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis Prospective study of oral microbiome and colorectal cancer risk in low-income and African American populations Detection of Campylobacter concisus and other Campylobacter species in colonic biopsies from adults with ulcerative colitis Detection and isolation of Campylobacter species other than C Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism Campylobacter gracilis and Campylobacter rectus in primary endodontic infections Metabolic property of acetaldehyde production from ethanol and glucose by oral Streptococcus and Neisseria Diversity of treponema denticola and other oral treponeme lineages in subjects with periodontitis and gingivitis Analysis of Fusobacterium nucleatum and Streptococcus gallolyticus in saliva of colorectal cancer patients Potential screening and early diagnosis method for cancer: tongue diagnosis Oral microbiome and history of smoking and colorectal cancer The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis a key pathogenic factor and microbial biomarker for colorectal cancer Fusobacterium nucleatum and colorectal cancer Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism Association between oral microbiota and cigarette smoking in the Chinese population Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data The SILVA ribosomal RNA gene database project: improved data processing and web-based tools Permutational Multivariate Analysis of Variance (PERMANOVA) In Wiley StatsRef: Statistics Reference Online Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach Importance of events per independent variable in proportional hazards analysis Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences Download references We thank Hong-Ling Sun and Huan Ren from Sun Yat-sen University Cancer Center for their help in participant enrollment This research was funded by the National Key Research and Development Program of China (2021YFC2500400) the National Natural Science Foundation of China (82404339 the Guang Dong Basic and Applied Basic Research Foundation (2023A1515110442 and 2025A1515010642) the Fundamental Research Funds for the Central Universities the Science and Technology Planning Project of Guangzhou and the Young Talent Support Project of Guangzhou Association for Science and Technology (QT2024-030) These authors contributed equally: Shi-Hao Zhou State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer and Y.L had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis carried out the statistical analysis; W.H.J obtained funding and supervised this project All authors revised the manuscript and approved the final manuscript The authors declare no competing interests Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41522-025-00702-0 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research The FDA has accepted Novo Nordisk’s new drug application (NDA) for a once-daily 25 mg oral formulation of Wegovy (semaglutide) for adults living with obesity and to reduce the risk of major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease Wegovy would become the first oral formulation of a GLP-1 indicated for chronic weight management A decision is expected in the fourth quarter of 2025 a phase 3 trial evaluating once-daily oral semaglutide 25 mg compared with placebo The trial enrolled 307 adults who were obese or who were overweight The trial included a 64-week treatment period including a 12-week dose escalation and a 7-week off-treatment follow-up period The trial found that once-daily oral semaglutide 25 mg reduced body weight and improved metabolic health in adults with overweight/obesity with comparable efficacy to semaglutide 50 mg in the OASIS 1 trial A greater proportion of participants achieved weight loss in the semaglutide group compared with placebo significant improvements in cardiometabolic risk factors were also observed with semaglutide vs placebo Adverse events leading to treatment discontinuation were comparable between groups Data from the OASIS 4 trial were presented in November 2024 at ObesityWeek2024 OASIS is a phase 3 clinical development program with once-daily oral semaglutide 25 mg and 50 mg in adults with obesity The program currently consists of four trials having enrolled approximately 1,300 adults with obesity or overweight with one or more comorbidities This news comes after results of several other oral GLP-1 therapies were released. Last week, Lilly reported positive topline phase 3 results from ACHIEVE-1 for orforglipron in adults with type 2 diabetes It also reduced weight by an average of 16.0 lbs (7.9%) at the highest dose in a key secondary endpoint The overall safety and tolerability profile of orforglipron in ACHIEVE-1 was consistent with injectable GLP-1 therapies Related: Liver Injury Ends Development of Pfizer’s Oral GLP-1 for Obesity But Pfizer stopped clinical development of its once-daily oral GLP-1 candidate to treat obesity Danuglipron was being studied for adults with obesity and without type 2 diabetes Company executives said that the overall frequency of elevated liver enzymes across the more than 1,400 participants in the clinical development program of danuglipron was in line with approved drugs in the class But in one of the dose optimization studies an asymptomatic patient experienced potential drug-induced liver injury which resolved after discontinuation of danuglipron Novo Nordisk already markets an oral semaglutide product Rybelsus is approved to treat type 2 diabetes It is available in both 7 mg and 14 mg and has a list price of $997.58 per package People with commercial insurance may pay as little as $10 for a one- Novo Nordisk reported the results of the SOUL trial which assessed Rybelsus 14 mg to lower cardiovascular risk in adults with type 2 diabetes This trial found that Rybelsus reduced the risk of major adverse cardiovascular events (MACE) by 14% compared with placebo in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD) These data were presented at the American College of Cardiology’s Annual Scientific Session and Expo Novo Nordisk has submitted a supplemental application to the FDA for Rybelsus 14 mg for this indication A regulatory decision is anticipated in 2025 FDA Approves Imaavy for Long Term Treatment of Generalized Myasthenia Gravis Adult and pediatric generalized myasthenia gravis patients have a new longer acting option for treatment called Imaavy CVS Caremark to Place Wegovy as Preferred GLP-1 for Weight Loss CVS Caremark will place Wegovy injection 2.4 mg as preferred on its commercial template formularies Oncologists: Prior Authorizations Lead to Delays in Getting Cancer Meds Insurance hurdles and the complexities of prior authorization create barriers to care according to oncologists in a new survey by Sermo Novo Nordisk Offers Wegovy Through Telehealth Providers, Including Hims & Hers Food Retailer Giant Eagle Selects EmpiRx Health as PBM Giant Eagle also helped EmpiRx Health create a national pharmacy care network that was purpose-built for pharmacy and grocery chains Part D Plans Cover a Larger Share of Medicare Beneficiaries in Rural Counties 609-716-7777 An Ohio.gov website belongs to an official government organization in the State of Ohio A lock or https:// means you've safely connected to the .gov website Share sensitive information only on official and personal information are protected by federal and state digital security standards Baits are dropped in northeastern Ohio to immunize wild raccoons for rabies In 1996, a new strain of rabies in wild raccoons was introduced into northeastern Ohio from Pennsylvania.  To protect Ohioans and their domestic animals the Ohio Department of Health (ODH) and other state and local agencies partnered with the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service Wildlife Services to implement a program to immunize wild raccoons for rabies using an oral rabies vaccine (ORV) This effort created a barrier of immune animals that reduced animal cases and prevented the spread of raccoon rabies into the rest of Ohio.  The vaccine-laden baits are dropped by fixed wing aircraft in rural areas and by low-flying helicopters and ground vehicles in urban and suburban neighborhoods Although placement is targeted to raccoon habitat it is inevitable that some baits may end up in a yard or be found by a pet or person.  Dogs are attracted to them.  Please refer to the information below if you or your pet finds a bait One type of bait will be used for the 2025 spring operation: The ONRAB® vaccine is enclosed in a 1" x 2" blister pack filled with the vaccine and covered with a sweet-smelling dark green waxy coating The baits contain a rabies vaccine that if consumed by a raccoon should vaccinate the animal against the rabies virus  ONRAB® does not contain rabies virus but contains a gene from the rabies virus that causes raccoons and skunks that come in contact with the vaccine to produce antibodies that protect them against rabies infection Ohio is one of seven states using ONRAB® for baiting operations in the U.S Ingesting the vaccine will not harm your pet although eating a large number may temporarily cause vomiting or diarrhea.  It is recommended to contact a veterinarian as a precaution if a pet has consumed the vaccine baits but intact baits can be moved if they are found in your lawn or other area where children and pets may find it.  Damaged baits should be bagged and disposed in the trash Contact with intact baits is not harmful.  Persons who are immunocompromised or pregnant should contact a physician if the bait ruptures and vaccine gets into a mucous membrane or open wound.  If a person is exposed to the vaccine (liquid) within the bait thoroughly wash any areas of the exposed skin with soap and warm water Working with employees from cooperating agencies USDA Wildlife Services distributes baits in urban area and suburban areas by vehicle or helicopter  The vaccines do not contain the live rabies virus but contains a gene from the rabies virus that causes raccoons and skunks that come in contact with the vaccine to produce antibodies that protect them against rabies infection The vaccine is contained inside a blister packet which is made attractive to wildlife with a sweet attractant.  When an animal bites into the bait it punctures the blister pack and the vaccine bathes the oral cavity and tonsils resulting in an oral vaccination against rabies.  The animal's immune system is exposed to the part of the rabies virus that causes an immune response and production of antibodies against rabies but the vaccine cannot cause rabies.  The blueprint for making antibodies to neutralize the rabies virus is stored in the animal's immune system allowing it to respond quickly if it is later exposed to a rabid animal Rabies Raccoons National Rabies Management Program Oral Rabies Vaccine Operation Daily Progress Map which the company hopes will be a powerful successor to Wegovy.Reporting by Sriparna Roy in Bengaluru; Editing by Sriraj Kalluvila Our Standards: The Thomson Reuters Trust Principles., opens new tab , opens new tab Browse an unrivalled portfolio of real-time and historical market data and insights from worldwide sources and experts. , opens new tabScreen for heightened risk individual and entities globally to help uncover hidden risks in business relationships and human networks. © 2025 Reuters. All rights reserved OKMULGEE, Okla – The Muscogee Creek Nation Supreme Court issued an order on April 28 resetting the oral arguments in SC-2023-20 Citizenship Board of the Muscogee Creek Nation v The oral arguments will be held on June 20 at 10 A.M Oral arguments in the case had originally been scheduled for July 26 The MCN SC issued a stay in the case on July 12 In the Matter of the Constitutionality of NCA 24-077 legislation on the process for appointing Special Justices the MCN SC issued the opinion that NCA 24-077 was unconstitutional This ruling resulted in the MCN SC order to rescind the stay and schedule oral arguments in SC-2023-10 arguments will not be available to the public: and/or reproductions of the Virtual Meeting and Oral Argument are strictly prohibited…IT IS FURTHER ORDERED that the Court will decline to consider any request for continuance of the virtual meeting or oral argument in this matter filed after 5:00 p.m. Mvskoke Media will have ongoing coverage of this story Comment * document.getElementById("comment").setAttribute( "id" "a202c56df7002b24b5262aaa5d310f78" );document.getElementById("f79d2c0fd6").setAttribute( "id" and website in this browser for the next time I comment Game Recap: Baseball | 5/4/2025 5:45:00 PM There are currently no upcoming/recent events Thanks for visiting The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here Human-Centered Design (HCD) is the process CMS uses to understand the people for which we are writing policies and creating programs and services At the center of CMS’ HCD process is participatory design and CMS employees to collaboratively understand the context of their work and engagement with CMS as well as the solutions we are creating to support them Findings are used to inform CMS’s policymaking and implementation processes CMS conducted the Oral Health Human-Centered Design Customer Engagement to understand barriers to oral healthcare access for Medicaid or dual (Medicare-Medicaid) eligible children and adults CMS engaged directly with a broad range of external customers through interviews and onsite visits to capture their lived experience we co-created the “Barriers to Oral Health” illustration with our external customers to represent their perspective and highlight the most prominent obstacles individuals’ face as they seek to access or provide oral healthcare The Oral Health Customer Engagement supports CMS’ Oral Health Cross-Cutting initiative View the Barriers to Oral Healthcare Illustration (PDF) Sign up for the Burden Reduction News & Insights newsletter Reach out to us to request a meeting with a CMS OHEI representative Request a meeting with us Request a CMS OHEI representative for your event Request a CMS OHEI rep Send us your ideas and get answers to your questions Contact us Sign up to get the latest information about your choice of CMS topics You can decide how often to receive updates A federal government website managed and paid for by the U.S Centers for Medicare & Medicaid Services Newsletters and Deep Dive digital magazine Novo Nordisk has pulled ahead in the race to bring the first oral GLP-1 for obesity to market The company announced Friday that the FDA has accepted its New Drug Application (NDA) submission for a once-a-day 25mg pill form of Wegovy (semaglutide) for chronic weight management The FDA action date is in Q4 of this year according to the company, who also stated in a release that the submission is based on strong data from the Phase 3 OASIS study, some of which was shared at ADA in 2023 "We are entering a new era of obesity care where patients want individualised treatment plans that address their needs and provide choices including oral formulations," said Anna Windle Semaglutide is already available in pill form under the name Rybelsus, but that drug, which cleared the FDA back in 2019 While Rybelsus sales haven't come anywhere near Ozempic's highs the drug has brought in $3.4 billion in sales for the company last year -- and the addressable market for obesity is much larger than diabetes pills are cheaper to manufacture and generally easier for patients to administer pharma companies see a weight loss pill as a winning prospect for standing out in an increasingly crowded market Novo Nordisk is in a race with several other companies to bring an oral GLP-1 for obesity to market, most notably Eli Lilly whose oral candidate orforglipron has also posted strong data recently. Lilly's CEO told Fortune in January he expects the drug to notch FDA approval in 2026 Another competitor, Pfizer's danuglipron had to halt its efforts last month after seeing signs of liver toxicity in late-stage clinical testing Roche and AstraZeneca have candidates as well but they're both considerably behind Lilly and Novo Nordisk Trump's 2026 budget request envisages sweeping cuts to funding for the NIH and other federal agencies that will be a disaster Shares in Eli Lilly have weakened after pharmacy benefit manager CVS Health said it would no longer cover its weight-loss therapy Zepbound Understanding how to harness real-world data and digital insights is essential The importance of biosimilars only continues to grow driven by the potential savings they are able to deliver to healthcare systems Jonah Comstock welcomed back Alice Valder Curran to the podcast to pick apart Trump's Executive Order order piece by piece Developments in the oncology space in 2024 brought hope to both industry and patients The ESG in Life Sciences Summit West is coming to San Francisco The ISPE Singapore Affiliate Conference & Exhibition is one of the largest and most respected events for bio & pharmaceutical manufacturing professionals opinions and features on pharma and healthcare sent straight to your inbox The UK is said to be preparing a £50m scheme to attract top scientific talent from other countries including US teams facing big funding cuts on Tuesday 28th January @ 10 am ET - 3 pm GMT - 4 pm CET entitled ‘Health Trends 2025: Reimagining What's Possibl Sign up for email newsletters and Deep Dive ROCHESTER — Share interesting tales from the past with storytellers Karen Chace and Andrea Lovett at the Carving Out Your Story oral history workshop Participants will uncover memories and tell stories through prompts and activities preserving these experiences “for future generations to enjoy.” The program is limited to 20 people and attendees can register online at https://www.plumblibrary.com/ Create a reading list by clicking the Read Later icon next to the articles you wish to save Asking scientists to identify a paradigm shift, especially in real time, can be tricky. After all, truly ground-shifting updates in knowledge may take decades to unfold. But you don’t necessarily have to invoke the P-word to acknowledge that one field in particular — natural language processing The goal of natural language processing is right there on the tin: making the unruliness of human language (the “natural” part) tractable by computers (the “processing” part) A blend of engineering and science that dates back to the 1940s Siri a brain and social media companies another way to target us with ads It was also ground zero for the emergence of large language models — a technology that NLP helped to invent but whose explosive growth and transformative power still managed to take many people in the field entirely by surprise To put it another way: In 2019, Quanta reported on a then-groundbreaking NLP system called BERT without once using the phrase “large language model.” A mere five and a half years later disruption and debate in whatever scientific community they touch But the one they touched first — for better worse and everything in between — was natural language processing What did that impact feel like to the people experiencing it firsthand Quanta interviewed 19 current and former NLP researchers to tell that story they describe a series of moments — dawning realizations elated encounters and at least one “existential crisis” — that changed their world By 2017, neural networks had already changed the status quo in NLP. But that summer, in a now-seminal paper titled “Attention Is All You Need,” researchers at Google introduced an entirely new kind of neural network called the transformer that would soon dominate the field ELLIE PAVLICK (assistant professor of computer science and linguistics Google DeepMind): Google had organized a workshop in New York for academics to hang out with their researchers He was making a really clear point about how aggressively this model was not designed with any insights from language Almost trolling a bit: I’m going to just talk about all these random decisions we made There had already been a feeling of the neural nets taking over and so people were very skeptical and pushing back University of Texas at Austin): It was sort of interesting It wasn’t like the next day the world changed I really do think it’s not conceptually the right model for how to process language I just didn’t realize that if you trained that very conceptually wrong model on a lot of data NAZNEEN RAJANI (founder and CEO, Collinear AI; at the time a Ph.D. student studying with Ray Mooney): I clearly remember reading “Attention Is All You Need” in our NLP reading group. Ray actually ran it, and we had this very lively discussion. The concept of attention had been around for a while and maybe that’s why Ray’s reaction was kind of I vividly remember members of the research team I was on asking “Should we look into these transformers?” and everyone concluding Stanford University): The transformers paper passed me by I think it would be very hard for anyone to tell from the paper what effect it was going to have Soon after it was introduced in October 2018, Google’s open-source transformer BERT (and a lesser-known model from OpenAI named GPT) began shattering the performance records set by previous neural networks on many language-processing tasks. A flurry of “BERTology” ensued with researchers struggling to determine what made the models tick while scrambling to outdo one another on benchmarks — the standardized tests that helped measure progress in NLP ANNA ROGERS (associate professor of computer science IT University of Copenhagen; editor-in-chief ACL Rolling Review): There was this explosion and everybody was writing papers about BERT I remember a discussion in the [research] group I was in: “OK we will just have to work on BERT because that’s what’s trending.” As a young postdoc I just accepted it: This is the thing that the field is doing student at the University of Washington): So many projects were dropped on the floor when BERT was released progress on these benchmarks went way faster than expected and we need to benchmark everything we can.” Some viewed this “benchmark boom” as a distraction Others saw in it the shape of things to come Anthropic; at the time an associate professor at New York University): When people submitted benchmark results and wanted to appear on the leaderboard I was often the one who had to check the result to make sure it made sense and wasn’t just someone spamming our system and I was noticing how much of it was just JULIAN MICHAEL: It became a scaling game: Scaling up these models will increase their ability to saturate any benchmark we can throw at them I don’t find this inherently interesting.” “Transformers aren’t going to get much better than BERT without new breakthroughs.” But it was becoming clearer and clearer for me that scale was the main input to how far this is going to go You’re going to be getting pretty powerful general systems So I got very interested in this question: All right what happens if you play that out for a few years As transformer models approached (and surpassed) “human baselines” on various NLP benchmarks, arguments were already brewing about how to interpret their capabilities. In 2020, those arguments — especially about “meaning” and “understanding” — came to a head in a paper imagining an LLM as an octopus Association for Computational Linguistics): I was having these just unending arguments on Twitter There was one about using BERT to unredact the Mueller report It seemed like there was just a never-ending supply of people who wanted to come at me and say LLMs really do understand.” It was the same argument over and over and over again I was talking with [computational linguist] Alexander Koller, and he said: “Let’s just write the academic paper version of this so that it’s not just ideas on Twitter And that’ll put an end to it.” It did not put an end to it Bender and Koller’s “octopus test” asserted that models trained only to mimic the form of language through statistical patterns could never engage with its meaning — much as a “hyperintelligent octopus” would never really understand what life was like on land even if it fluently reproduced the patterns it observed in human messages SAM BOWMAN: This argument — that “there’s nothing to see here,” that neural network language models are fundamentally not the kind of thing that we should be interested in that a lot of this is hype — that was quite divisive JULIAN MICHAEL: I got involved in that. I wrote this takedown of the paper — it was the one blog post I’ve ever written I worked hard to make it a good-faith representation of what the authors were saying I even got Emily to read a draft of my post and correct some of my misunderstandings Ellie Pavlick (assistant professor of computer science and linguistics ELLIE PAVLICK: These “understanding wars” — to me that’s when a reckoning was really happening in the field Meanwhile, another reckoning — driven by real-world scale, not thought experiments — was already underway. In June of 2020, OpenAI released GPT-3 a model more than 100 times as large as its previous version and much more capable GPT-3 was the moment when everything changed CHRISTOPHER CALLISON-BURCH (professor of computer and information science University of Pennsylvania): I got early access to the GPT-3 beta and was actually playing with it myself I’m trying out all the things that my recent Ph.D the thing that had taken a student five years Seems like I could reproduce that in a month many of which I had touched on or actively researched throughout my career I sometimes describe it as having this career-existential crisis “Should women be allowed to vote?” it would say no But the fact that you could just teach it to do a completely new task in three or four lines of natural language was mind-boggling CHRISTOPHER POTTS: Somebody in our group got early access to the GPT-3 API thinking: I’m going to prompt it with some logic questions and it’s going to fail at them I’m going to reveal that it has just memorized all the things that you’re so impressed by I’m going to show you that this is a party trick this is definitely much more than a party trick.” Stanford University; 2022 MacArthur fellow): It was still broken A lot of commonsense knowledge [coming] out of GPT-3 was quite noisy R. THOMAS MCCOY: This GPT-3 paper was sort of like the series finale of “Game of Thrones.’’ It was the thing that everyone had just read and everyone was discussing and gossiping about University of Pennsylvania): It almost was like we had a secret and everyone you shared it with was blown away All I had to do was bring someone over to my laptop JULIAN MICHAEL: BERT was a phase transition in the field A system that produces language — we all know the ELIZA effect But it also did more to change the practical reality of the research that we did — it’s like you can do anything [with this].” What are the implications of that OpenAI did not publicly release GPT-3’s source code disruptive capability and corporate secrecy put many researchers on edge SAM BOWMAN: It was bit of a divisive moment because GPT-3 was not really coming from the NLP community It was really frowned upon for a while to publish results of studies primarily about GPT-3 because it was [seen as] this private artifact where you had to pay money to access it in a way that that hadn’t usually been the case historically ANNA ROGERS: I was considering making yet another benchmark Let’s say GPT-3 either can or cannot continue [generating] these streams of characters but that’s not actually even a machine learning research question “API science,’’ that people would use to be like: “We’re doing science on a product it’s not reproducible.” And other people were like: “Look TAL LINZEN (associate professor of linguistics and data science Google):  For a while people in academia weren’t really sure what to do This ambivalence was even shared by some within industry labs such as Microsoft Microsoft Research India): The Microsoft leadership told us pretty early on that this was happening It felt like you were on some rocket being thrown from Earth to the moon it was going at a pace that meant you really had to look at all your navigation instruments to make sure you’re still headed in the right direction an AI ethics researcher at Google] approached me in a Twitter DM exchange asking if I knew of any papers about the possible downsides of making language models bigger and bigger she saw people around her constantly pushing: “OpenAI’s is bigger We’ve got to make ours bigger.” And it was her job to say The paper that Bender subsequently wrote with Gebru and her colleagues — “On the Dangers of Stochastic Parrots: Can Language Models Be Too Big?” — injected moral urgency into the field’s core (and increasingly sore) arguments around form versus meaning and method versus scale KALIKA BALI: Some of the points that Emily makes are things that we should be thinking about That was the year that the NLP community suddenly decided to worry about how it had neglected everything except the top five languages in the world — nobody ever talked about these things earlier But what I did not like was that the entire NLP community kind of organized themselves for and against the paper JULIE KALLINI (second-year computer science Ph.D Stanford University): As a young researcher I was an undergraduate at Princeton University I remember distinctly that different people I looked up to — my Princeton research adviser [Christiane Fellbaum] versus professors at other universities — were on different sides KALIKA BALI: It was positive that that paper came out but it was also stressful to see people that you really respect drawing swords at each other the tension arises: If you want to do research that has any sort of lasting impact more than two or three years after you publish Because it dictates so much of the way that you even look at problems Usually you just subscribed to Substacks to see the angry linguistics side and you’d go on Twitter to see the pro-scaling side JEFF MITCHELL (assistant professor in computer science and AI University of Sussex): It felt a little abnormal As scale-driven research continued to accelerate, some felt that discourse within the field was seriously deteriorating. In an attempt to repair it, the NLP research community surveyed itself in the summer of 2022 on “30 potentially controversial positions” — including “Linguistic structure is necessary,” “Scaling solves practically any important problem” and “AI could soon lead to revolutionary societal change.” SAM BOWMAN: The industry community that was doing a lot of this early work around scaling had never been that closely engaged with academic NLP That led to a divergence in understanding and what people thought was happening between these two [groups] because they weren’t talking to each other that much LIAM DUGAN: They gave a large part of the survey out at ACL [Association for Computational Linguistics This was the first conference I’d ever been to and it was very exciting for me because there’s all these people that are really smart JULIAN MICHAEL: It was already a field in crisis LIAM DUGAN: You got to see the breakdown of the whole field — the sides coalescing The linguistic side was not very trusting of raw LLM technology There’s a side that’s sort of in the middle And then there’s a completely crazy side that really believed that scaling was going to get us to general intelligence On November 30, 2022, OpenAI launched its experimental chatbot ChatGPT hit the NLP community like an asteroid Allen Institute for AI; chief scientist and co-founder a lot of the problems that a large percentage of researchers were working on — they just disappeared CHRISTOPHER CALLISON-BURCH: I didn’t predict it But I was prepared for it because I had gone through that experience with GPT-3 earlier THOMAS MCCOY: It’s reasonably common for a specific research project to get scooped or be eliminated by someone else’s similar thing But ChatGPT did that to entire types of research A lot of higher categories of NLP just became no longer interesting — or no longer practical — for academics to do SAM BOWMAN: It felt like the field completely reoriented IZ BELTAGY: I sensed that dread and confusion during EMNLP [Empirical Methods in Natural Language Processing] Everybody was still shocked: “Is this going to be the last NLP conference?” This is actually a literal phrase that someone said During lunches and cocktails and conversations in the halls everybody was asking the same question: “What is there that we can work on?” NAZNEEN RAJANI: I had just given a keynote at EMNLP who was my manager at Hugging Face and also one of the co-founders can you get on a call with me ASAP?” He told me that they had fired people from the research team and that the rest would either be doing pre-training or post-training — which means that you are either building a foundation model or you’re taking a foundation model and making it an instruction-following model “I recommend you pick one of these two if you want to continue at Hugging Face.” It didn’t feel like what the Hugging Face culture stood for everyone was basically just doing their own research Rude awakenings also came from the bottom up — as one eminent NLP expert found out firsthand while teaching her undergraduate course in the weeks after ChatGPT’s release CHRISTIANE FELLBAUM (lecturer with the rank of professor of linguistics and computer science Princeton University): We had just started our semester a student whom I didn’t know yet came up to me showed me a paper with my name and title on it and said: “I really want to be in your class — I’ve researched your work and I have found this paper from you sure.” I was flattered: He’s researching me And while I was trying to refresh my memory “What’s funny?” And he said: “This paper was written by ChatGPT ‘Write me a paper in the style of Christiane Fellbaum,’ and this is what came out.” because I had to start class in 10 minutes But everything looked like what I would write ChatGPT threatened their research projects and possibly their careers CHRISTOPHER CALLISON-BURCH: It helps to have tenure when something like this happens But younger people were going through this crisis in a more visceral way students literally formed support groups for each other it’s like there’s nothing intellectual about them left Just kind of dragging your feet or getting very cynical RAY MOONEY: One of my own [graduate students] thought about dropping out They thought that maybe the real action was happening in industry and not in academia I was really unsure about where my direction would end up I tried to make sure that I know my machine learning fundamentals well It’s not the wisest thing to only specialize in potentially fleeting trends in large language models NLP researchers from Seattle to South Africa faced a firehose of global attention SAM BOWMAN: It goes from a relatively sleepy field to I’m having lunch with people who were meeting with the Pope and the President in the same month I counted five workdays with no media contact ELLIE PAVLICK: Before ChatGPT, I don’t think I ever talked to a journalist. Maybe once or twice. After ChatGPT, I was on 60 Minutes It was a huge qualitative difference in the nature of the work CHRISTOPHER CALLISON-BURCH: I felt like my job went from being an academic with a narrow audience of graduate students and other researchers in my field to being like, “Hey, there’s an important responsibility for scientific communication here.” I got invited to testify before Congress I was suddenly being asked for my opinion in interviews “I’m such an expert in this!” Then it felt less exciting and more sort of overwhelming: “Where do you see this going in the future?” I don’t know But it’s crazy: There’s thousands of papers Everyone has their hot take on what’s going on And most of them have no idea what they’re talking about SAM BOWMAN: There was this flowering of great engagement: Suddenly a lot of really amazing people from a lot of fields were looking at this stuff And it was also getting drowned out in noise: everyone talking about this stuff all the time lots and lots of really dashed-off takes that didn’t make any sense NAZNEEN RAJANI: That year was kind of a roller coaster the annual EMNLP conference convened again in Singapore LIAM DUGAN: The temperature was just so much higher and the flood of arxiv [preprint] results was just so intense You would walk the halls: All the way down it was just prompting and evaluation of language models it felt like there were more people there than good research ideas the LLM-generated writing was on the wall — and it said different things to different people in the field THOMAS MCCOY: Anytime you’re doing work that asks about the abilities of an AI system you ought to be looking at systems for which we have access to the training data But that’s not at all the prevalent approach in the field we’ve become more “LLM-ologists” than scientists I often say this when I give talks: “Right now we are studying language models.” I get how myopic that seems But you have to see this really long-game research agenda where it fits there’s not a path forward to understanding language that doesn’t have an account of “What are LLMs doing?” KALIKA BALI: Every time there’s been a technological disruption that mainly comes from the West there’s always been these — if you may call it — philosophical concerns “How do we make it work for us here and now?” the initial idea that everyone gathered around [after ChatGPT came out] was to have generative language models do their work in English and then put a translation system in front of it to output into whatever language you wanted But machine translation systems are literal “John and Mary have a key lime pie to divide,” and you translate it into Hindi I can bet you most people in India do not know what a key lime pie is How would you translate that into something culturally specific unless the model itself is made to understand things I became much more interested in how to solve that IZ BELTAGY: There is a point where you realize that in order to continue advancing the field Like the Large Hadron Collider — you can’t advance experimental physics without something like this which generally has more resources than most academic labs ChatGPT made it clear that there’s a huge gap between OpenAI and everybody else we started thinking about ways we can build these things from scratch In 2024, Ai2’s OLMo provided a fully open-source alternative to the increasingly crowded field of industry-developed language models some researchers who had continued to study these proprietary systems — which only grew in scale capability and opaqueness in the post-ChatGPT AI boom — were already encountering a new kind of resistance YEJIN CHOI: I had this paper [in late 2023] demonstrating how the latest GPT models, which were seemingly good at doing multiplication, suddenly get very bad at it when you used three- or four-digit numbers People who don’t do empirical research at all were saying “Did you do your experiments correctly?” That had never happened before I was just surprised by how powerful this thing is Ungrounded hype isn’t helpful in science. I felt it was important to study the fundamental limits and capabilities of LLMs more rigorously, and that was my primary research focus in 2024. I found myself in a weird situation where I was becoming the negative naysayer for how the models cannot do this and that. Which I think is important — but I didn’t want it to be all that I do. So I’m actually thinking a lot about different problems these days TAL LINZEN: It’s sometimes confusing when we pretend that there’s a scientific conversation happening but some of the people in the conversation have a stake in a company that’s potentially worth $50 billion money and hype vaporized the already-porous boundaries between NLP and AI Researchers contended with a new set of incentives and opportunities — not just for themselves NAZNEEN RAJANI: It opened doors that wouldn’t have otherwise I was one of the first people to get the data to reproduce ChatGPT in open-source — I basically wrote the recipe book for it And that led me to get a good seed round for my startup THOMAS MCCOY: Any faculty member who is AI-adjacent starts to be viewed as an AI person — you sort of get typecast to play that role I’m happy to work on AI because it’s one of the most impactful things that I can be doing with my skillset But the thing that would bring me the greatest joy is diving deeply into interesting corners of grammar and human cognition Which is something that can be linked back to advancing AI JULIE KALLINI: It’s all a matter of semantics computational linguistics and AI at the same time I do think there are different communities for each field but there are plenty of people who bridge several areas And I think to some extent that’s happened Basically that’s because I don’t think we’ve actually solved the problem The only reason to get upset is if you think: “This is it Language is done.” And I don’t think that’s true CHRISTOPHER POTTS: This should be an incredible moment for linguistics and NLP Maybe it’s one of those moments of a field waking up and realizing that it now has incredible influence You can’t pretend like you’re a quiet scientific or engineering field anymore that just does research for the sake of research — because now all the money in the world is behind you and every big corporation is trying to exert influence on what you do and language models are being deployed all over the place you also have to accept that the debates are going to be heated I would never have thought that just typing an instruction into a language model would get it to complete the sentence in a way that is consistent with what you’re asking it to do I don’t think anyone would have thought that that would be the paradigm these days We have this one interface that basically lets us do everything Back from the word-embedding days [in 2013] the whole premise was transfer learning — you learn something from a large amount of textual data in the hope that this will help you with something else in how the public feels about this — but not in this underlying principle JEFF MITCHELL: I feel like the corporate interests have changed the way the game is played ELLIE PAVLICK: I think the media involvement makes a difference Scientists in my field realized that success could look like becoming known outside of NLP Papers on arxiv.org are often titled to be picked up by journalists or Silicon Valley enthusiasts VUKOSI MARIVATE: I think in some ways the barrier to entry both got reduced and heightened The reduced part is that there’s still a lot that we just don’t understand about what’s actually going on in these systems so there’s a lot of work that’s just prodding them as much as possible you don’t need to know the architecture of a neural network like the back of your hand the barrier was heightened because in order to play with and prod those architectures you have to be in a very high-resource space BENDER: I have seen an enormous shift towards end-to-end solutions using chatbots or related synthetic text-extruding machines is that these large language models are getting so powerful that we have to ask “Where does the human fit in?’’ That’s a paradigm shift: a shift in technology how these models are trained and how well they can learn And then of course the educational consequences Those are the things that keep me awake at night there are all these questions that historically have been largely philosophical debates that suddenly are empirically testable That’s definitely been one big paradigm shift the way the field looked like 10 years ago was: people creating some data set And that version of the field still exists just with much larger data sets and much larger neural networks CHRISTOPHER POTTS: Maybe this is the way it always works but the hallmark of a paradigm shift is that questions we used to think were important now no longer get asked It feels like that has happened over the past five years I used to focus a lot on sentiment classification “Give me a sentence and I’ll tell you if it was expressing a positive or negative emotion.’’ Now the entire field is focused on natural language generation — all those questions that we used to think were central have become peripheral compared to that we’ll look back and think this was nothing compared to what happened in 2029 All conversations have been edited for length and clarity Quanta Magazine moderates comments to facilitate an informed incoherent or off-topic comments will be rejected Moderators are staffed during regular business hours (New York time) and can only accept comments written in English We’ll email you instructions to reset your password you may be swapping your GLP-1 injections for easier and as-effective oral weight-loss medication It's also likely to be cheaper and not suffer the same kind of supply-chain shortages that existing therapeutics have faced But it's been a dramatic few weeks for the leading three drug-makers vying to usher in this new phase of weight-loss treatment And while it's only a matter of time until Ozempic-like drugs are available as oral medication the past few weeks have seem one small victory and a huge setback for some of the big players in the field Amid profits updates and shareholder news, Pfizer released a statement titled "Pfizer provides update on oral GLP-1 receptor agonist danuglipron." The company quietly announced that it was ditching its once-daily oral drug due to liver toxicity concerns following analysis of Phase III trial data "While the overall frequency of liver enzyme elevations across the over 1,400 participant safety database of danuglipron is in-line with approved agents in the class a single asymptomatic participant in one of the dose-optimization studies experienced potential drug-induced liver injury which resolved after discontinuation of danuglipron," Pfizer said in the statement Little more is known about the specifications of the liver injury but the participant experienced elevated enzymes in the organ But we're unlikely to know more until the trial data is "presented at a scientific forum or submitted for publication in a peer-reviewed journal in the future." “While we are disappointed to discontinue the development of danuglipron we remain committed to evaluating and advancing promising programs in an effort to bring innovative new medicines to patients," said Chris Boshoff In December 2023 Pfizer scrapped development of a twice-daily danuglipron drug because of adverse side effects that included nearly 50% of participants experiencing vomiting However, the ones to watch are Eli Lilly and Novo Nordisk, which now have their own GLP-1 oral drugs nearing the finish line. Just three days after the Pfizer news, Eli Lilly announced positive results from its Phase III trial of weight-loss drug candidate orforglipron these results are just one part of the Phase III evaluation with the drug being assessed for bot diabetes and obesity treatment "[The trial] ACHIEVE-1 is the first of seven Phase II studies examining the safety and efficacy of orforglipron across people with diabetes and obesity We are pleased to see that our latest incretin medicine meets our expectations for safety and tolerability and we look forward to additional data readouts later this year," said David A could be readily manufactured and launched at scale for use by people around the world." orforglipron is a small molecule (non-peptide) oral drug designed to be taken anytime the 40-week trial saw participants with type 2 diabetes lose an average of 16 pounds (7.25 kg) The company is expected to apply for Food and Drug Administration approval this year with the suite of Phase III results expected by the end of 2025 or early 2026 Finally, and the most likely company to get the first oral GLP-1 drug to market, Novo Nordisk has had a big win this week, with the US Food and Drug Administration (FDA) accepting its application for review the Danish pharmaceutical giant is understandably confident the drug will pass its final hurdle Medical & Regulatory Affairs at the company passed its final safety and efficacy tests in its 64-week OASIS 4 Phase III trial which involved 307 adults who were overweight or obese and did not have diabetes The FDA's decision on oral Wegovy is expected as early as October 2025 Novo Nordisk already has an oral semaglutide drug on the market but it's only approved for diabetes management Game Recap: Baseball | 5/3/2025 5:24:00 PM Thanks for visiting Metrics details This work prioritizes Indigenous control of genetic data and brings together oral tradition with smoothing applied to produce derivative hillshade and terrain-relief datasets they also acknowledge uncertainties because of gaps in their oral history Such gaps are inevitable in a centuries-old community that by our estimate (below) lost at least 85% of their members in the first several decades after European Contact the community had shrunk to around 300 members making them the smallest of the extant Pueblo nations centuries of oppression and prohibition of Picuris religion and rituals the loss of access to traditional and sacred landscapes and the placement of Picuris children into Native American boarding schools inhibited the intergenerational transmission of cultural knowledge and history at Picuris these factors have often minimized Picuris’ voice in continuing discussions regarding the status and future of Chaco Canyon The Picuris community initiated this research to bridge and mend gaps in their traditional knowledge with appropriate scientific data and to address the extent to which they might have ancestral ties to Chaco Canyon and the regional system it anchored centuries ago that were on long-term loan to Southern Methodist University we have chosen to address both the Picuris Pueblo Tribal Nation and its members in the third person even though some of its members are coauthors of this study Picuris trace their origins to an underground realm inhabited by Pá à wíá è Páyó The community is divided in two halves (the ‘North’ and ‘South’ people) which have separate birthplaces in Picuris oral histories with the earliest peoples emerging from lakes near big white mountains One of those lakes is called Phaxwii Oxwalna The geographical correspondence of the ‘North’ people’s emergence location is less clear with some traditions identifying it as a spring near Pikes Peak After migrating through the landscape for an unknown duration of time these peoples settled at Picuris and Taos Pueblos Archaeological estimates put the founding of these communities at roughly 900 ce Although Pot Creek Pueblo was depopulated in roughly 1320 ce communities that speak closely related languages continuously occupied communities in the Americas when directly testing whether those populations carry instead ancestry from the other lineage in the form D(pop USR1.11,500 bp) we found all to be consistent with zero (maximum D = 0.011 Z = 1.82 for LaPlaya.600 bp and ‘CanAmerindian_1’) suggesting our dataset does not include a suitable proxy for the excess ancestry not represented in Anzick1 found in Picuris and other populations This probably represents either ancestry more basal than the one found in the Anzick1 genome or an ancestry source very distantly related to the ones with genetic data available the average shared IBD segments longer than 8 centiMorgans (cM) between Indigenous American populations and present-day individuals from Picuris Pueblo Populations are ordered by latitude and coloured by major geographic areas the demographical history of present-day Picuris individuals inferred using HapNe-LD with imputed diploid genotypes Shaded areas show 95 and 90% confidence intervals The x axis is the time (measured in generations ago since the time of sampling) and the y axis the effective population size (Ne) 5,480 using HapNe-LD) are consistent with estimates of around 10,000 individuals being part of the Picuris sphere of influence at the time The estimate of around 3,000 people at Picuris Pueblo is supported by oral traditions at Picuris as well as archaeological estimates based on ceramic frequencies and architectural space occupied at the site’s maximal size and arrival times in those regions have been of longstanding academic debate error bars represent about 3.3 standard errors (P ≈ 0.001 in a Z test with 172,863 SNPs in 5-Mb jackknife blocks) These results support a late arrival of Athabascan-related populations in the US Southwest or admixture evident in Southern Athabascans could have been one-directional Although this would explain the absence of an Athabascan ancestry signal in ancient Picuris given the extensive interactions between those two groups it is unlikely that such a scenario persisted over an extended period we show that individuals from Picuris Pueblo are the closest sampled population challenging claims of depopulation or disappearance in the area and establishing a genetic component to suspected cultural affiliation between a present-day group and Ancestral Puebloan heritage We emphasize that this conclusion does not challenge or call into question the connections and relationships that more than two dozen federally recognized Tribes have to Chaco Canyon the only example of paleogenetic data supporting a federally recognized Tribe’s affiliation with Chaco Canyon ancestors Their application can have profound restorative value for present-day communities discussions of their cultural heritage and ensure their federally recognized rights as stakeholders of ancient sites We hope collaborative efforts such as this one serve as catalysts for meaningful action and policy consideration greater respect for oral histories and traditions and that these results can be incorporated into well informed decision-making processes affecting Tribal sovereignty and community identity Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Analyses were done using freely available software, which have been fully referenced throughout the paper and Supplementary Information. Custom code can be found on https://github.com/abigailramsoe/lundbeck-pipeline Chaco Canyon dig unearths ethical concerns Genomic research through an indigenous lens: understanding the expectations Ancient-DNA researchers write their own rules The genome of a Late Pleistocene human from a Clovis burial site in western Montana The ancestry and affiliations of Kennewick Man Early human dispersals within the Americas Ancient and modern genomics of the Ohlone Indigenous population of California Genomic analyses correspond with deep persistence of peoples of Blackfoot Confederacy from glacial times Archaeogenomic evidence reveals prehistoric matrilineal dynasty The rise and fall of the prehistoric population of Northern Arizona Collapse: How Societies Choose to Fail or Succeed (Penguin Later Athapaskan prehistory: a migration hypothesis Gateways for Athabascan migration to the American Southwest A Theory of Northern Athapaskan Prehistory (Routledge World Heritage in the United States. National Park Service www.nps.gov/subjects/internationalcooperation/worldheritage.htm (2024) Ancient Puebloan Southwest (Cambridge Univ and the reorganization of the Pueblo World Ecosystem impacts by the Ancestral Puebloans of Chaco Canyon Pueblo Nations: Eight Centuries of Pueblo Indian History (Clear Light Thoughts on migration by Santa Clara Pueblo Native American perspectives of the past in the San Pedro Valley of Southeastern Arizona They go along singing: reconstructing the Hopi past from ritual metaphors in song and image Memory pieces and footprints: multivocality and the meanings of ancient times and ancestral places among the Zuni and Hopi Identity as history: Hopi clans and the curation of oral tradition Some contemporary pueblo perspectives on archaeology in the Pueblo world The Cave in the Kiva: the Kiva Niche and painted walls in the Rio Grande Valley A symmetry analysis of design structure: 1,000 years of continuity and change in Puebloan ceramic design An Archaeology of Doings: Secularism and the Study of Pueblo Religion (School for Advanced Research Press in The Oxford Handbook of Southwest Archaeology (eds Mills Signs from the Ancestors: Zuni Cultural Symbolism and Perceptions of Rock Art (Univ Archaeology and Native North American oral traditions Archaeology and oral tradition: the scientific importance of dialogue Truth dwells in the deeps: Southwestern oral traditions and archaeological interpretations Truth and the Hopi: an historiographic study of documented oral tradition concerning the coming of the Spanish Western Apache oral histories and traditions of the Camp Grant Massacre Ancient history in the New World: integrating oral traditions and the archaeological record in deep time Extraction of highly degraded DNA from ancient bones teeth and sediments for high-throughput sequencing Improving access to endogenous DNA in ancient bones and teeth Meyer, M. & Kircher, M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb. Protoc. https://doi.org/10.1101/pdb.prot5448 (2010) Manual and automated preparation of single-stranded DNA libraries for the sequencing of DNA from ancient biological remains and other sources of highly degraded DNA Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA Patterns of damage in genomic DNA sequences from a Neandertal A revised timescale for human evolution based on ancient mitochondrial genomes ANGSD: analysis of next generation sequencing data A likelihood method for estimating present-day human contamination in ancient male samples using low-depth X-chromosome data Efficient phasing and imputation of low-coverage sequencing data using large reference panels Population genomics of post-glacial western Eurasia Reconstructing Native American population history Genomic evidence for the Pleistocene and recent population history of Native Americans Identity by descent between distant relatives: detection and applications Inference of population splits and mixtures from genome-wide allele frequency data Human Y-chromosome variation in the genome-sequencing era Maternal ancestry and population history from whole mitochondrial genomes Peopling of the Americas as inferred from ancient genomics Terminal Pleistocene Alaskan genome reveals first founding population of Native Americans Ancient human parallel lineages within North America contributed to a coastal expansion Reconstructing the deep population history of Central and South America Deep genetic affinity between coastal Pacific and Amazonian natives evidenced by Australasian ancestry Genetic continuity and change among the Indigenous peoples of California Demographic history and genetic structure in pre-Hispanic Central Mexico Accurate non-parametric estimation of recent effective population size from segments of identity by descent Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals Haplotype-based inference of recent effective population size in modern and ancient DNA samples Picuris Pueblo through Time: Eight Centuries of Change in a Northern Rio Grande Pueblo (William P A Brief History of Picuris Pueblo: A Tiwa Indian Group in North Central New Mexico (Alamosa Inbreeding and variance effective numbers in populations with overlapping generations Effective population size/adult population size ratios in wildlife: a review The Languages of Native North America (Cambridge Univ Dinétah: An Early History of the Navajo People (Sunstone Moving on: expanding perspectives on Athapaskan migration Coronado’s Querechos and Teyas in the archaeological record of the Texas Panhandle The Little Ice Age in the Canadian Rockies Global signatures and dynamical origins of the Little Ice Age and Medieval climate anomaly Assessing the performance of qpAdm: a statistical tool for studying population admixture Social Life of the Navajo Indians: With Some Attention to Minor Ceremonies (Columbia Univ in Studies in Language Companion Series Vol et al.) 301–318 (John Benjamins Publishing Company Genomic insights into the origin and diversification of late maritime hunter-gatherers from the Chilean Patagonia Origins and genetic legacies of the Caribbean Taino Archaeogenomic distinctiveness of the Isthmo-Colombian area Barquera, R. et al. Ancient genomes reveal insights into ritual life at Chichén Itzá. Nature https://doi.org/10.1038/s41586-024-07509-7 (2024) Summer internship for INdigenous peoples in Genomics (SING) Consortium et al A framework for enhancing ethical genomic research with Indigenous communities Community partnerships are fundamental to ethical ancient DNA research Earth Resources Observation and Science (EROS) Center. USGS EROS Archive—Digital Elevation—Shuttle Radar Topography Mission (SRTM) Void Filled. USGS https://doi.org/10.5066/F7F76B1X (2018) The IntCal20 Northern Hemisphere radiocarbon age calibration curve (0–55 cal kBP) Fast and accurate short read alignment with Burrows-Wheeler transform mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters The Sequence Alignment/Map format and SAMtools HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing MAFFT Multiple Sequence Alignment Software Version 7: improvements in performance and usability scalable and user-friendly tool for maximum likelihood phylogenetic inference BEAST 2: a software platform for Bayesian evolutionary analysis Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females Y Chromosome sequences reveal a short Beringian standstill and early population structure Native American Founders Ancient genomes reveal long-range influence of the pre-Columbian culture and site of Tiwanaku Genomic evidence for ancient human migration routes along South America’s Atlantic coast Ancient human genome sequence of an extinct Palaeo-Eskimo Integration of ancient DNA with transdisciplinary dataset finds strong support for Inca resettlement in the south Peruvian coast The genetic prehistory of the Andean highlands 7000 years BP through European Contact Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans The population history of northeastern Siberia since the Pleistocene Palaeo-Eskimo genetic ancestry and the peopling of Chukotka and North America The Simons Genome Diversity Project: 300 genomes from 142 diverse populations Insights into human genetic variation and population history from 929 diverse genomes The genetic prehistory of the New World Arctic Genomic evidence for adaptation to tuberculosis in the Andes before European contact High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography A genetic history of the pre-contact Caribbean Genomic insights into the early peopling of the Caribbean Life and death in early colonial Campeche: new insights from ancient DNA A Paleogenomic reconstruction of the deep population history of the Andes South-to-north migration preceded the advent of intensive farming in the Maya region Dissecting the pre-Columbian genomic ancestry of Native Americans along the Andes–Amazonia divide Patterns of admixture and population structure in native populations of Northwest North America The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture PLINK: a tool set for whole-genome association and population-based linkage analyses RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference Moreno-Mayar, J. V. FrAnTK: a Frequency-based Analysis ToolKit for efficient exploration of allele sharing patterns in present-day and ancient genomic datasets. G3 https://doi.org/10.1093/g3journal/jkab357 (2021) On the limits of fitting complex models of population history to f-statistics Detecting identity by descent and estimating genotype error rates in sequence data The spatiotemporal patterns of major human admixture events during the European Holocene Download references We dedicate this paper to the memory of Richard Mermejo as well as the Tribal liaison of this project We thank Picuris Pueblo Tribal council for their support for the project for providing a stimulating environment of discussion and learning The Lundbeck Foundation GeoGenetics Centre is supported by grants from the Lundbeck Foundation (grant nos the Danish National Research Foundation (grant nos the University of Copenhagen (KU2016 programme) and Ferring Pharmaceuticals A/S to E.W is funded by the National Science Foundation (grant no is funded by the Queen Margrethe’s and Vigdís Finnbogadóttir’s Interdisciplinary Research Centre on Ocean CNPq 406864/2022-5 and FAPEMIG APQ-00220-22 from Brazil is funded by the Quest Archaeological Research Fund and the Potts & Sibley Foundation is funded by the European Research Council (grant no These authors contributed equally: Thomaz Pinotti These authors jointly supervised this work: David J Laboratório de Biodiversidade e Evolução Molecular (LBEM) Center for Molecular Anthropology for the Study of Ancient DNA Department of Archaeology and Classical Studies MARUM Center for Marine Environmental Sciences developed and maintained bioinformatic infrastructure did laboratory work and data generation (with support from M.F analysed sequence data (with support from G.S led community engagement (with support from T.P. provided archaeological curation and context were involved in conceptualizing the draft and final version wrote the initial draft with significant input from D.G All authors revised and agreed on the final submitted version Nature thanks the anonymous reviewers for their contribution to the peer review of this work The high branch lengths in some populations may reflect analytical artifacts: for ancient individuals they arise from high error rates due to low coverage and DNA damage they result from missing data caused by masking non-Indigenous American segments Present-day literature mitogenomes are in black present-day Picuris in blue and all other ancient mitogenomes in gold Near-zero length branches were collapsed for convenience Ancient Picuris are in red and present-day Picuris in blue Relevant literature individuals appear in italic In accordance with Picuris wish to not have its data included in any private database we do not describe any variant private to them Supplementary Table 1: Per library sequencing summary statistics Supplementary Table 2: Per individual sequencing summary statistics Supplementary Table 3: Present-day Picuris individuals sequencing summary statistics Supplementary Table 4: Reference genomic dataset summary statistics Supplementary Table 5: Reference hybridization capture dataset Supplementary Table 6: Reference array dataset Download citation DOI: https://doi.org/10.1038/s41586-025-08791-9 Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology Game Recap: Baseball | 5/2/2025 10:54:00 PM Thanks for visiting Law students are seen with Federal Circuit judges following a special sitting at North Carolina Central University School of Law Law students were asked to set aside their casebooks to witness “justice in action” as Federal Circuit judges and attorneys recently gathered for oral arguments at three North Carolina law schools.  “This program has universal benefits,” said Chief Judge Kimberly A who participated in a series of oral arguments in North Carolina “It serves an important civic education function while at the same time reenforcing for judges the importance of the court’s mission not only to the litigants whom it serves but also to the next generation of aspiring lawyers.” Over 100 eager law students from North Carolina Central University School of Law the University of North Carolina School of Law and Duke University School of Law gathered in campus auditoriums in February to watch as judges and attorneys deliberated cases involving patent and government contract disputes.  visit Duke University School of Law for a special sitting Credit: Duke University School of Law.      has exclusive nationwide jurisdiction over a variety of subject areas as well as a statutory requirement to provide citizens with reasonable opportunities to appear before the court This creates a unique opportunity to hold oral arguments outside of D.C. including most recently in the San Francisco Bay Area and in Boston later this fall “The court believes that by engaging with the public through this program it can promote transparency and increase public trust and confidence in the Federal Circuit and the Judiciary,” Moore said Federal courts of appeals across the country regularly conduct special sittings at law schools to provide law students with real-life exposure to a sitting panel of judges A question-and-answer session often follows oral arguments as law students are able to gain valuable insights into career paths in the justice system visit the University of San Diego (USD) School of Law for a special sitting "Sitting at law schools gives the students a chance to see the court up close and personal,” said Judge M. Margaret McKeown, of the U.S. Court of Appeals for the Ninth Circuit, who recently participated in oral arguments at University of San Diego School of Law “We follow the arguments with a lively question and answer session and then a lunch with the students What better way to spend our time than with the next generation of lawyers?”  “The energy that law students bring to argument — as advocates or merely spectators — is very special,” said Judge John B who also took part in the special sitting in San Diego “I always look forward to law school sittings and hope this important tradition continues.”  Learn more about the U.S. courts of appeals. This purchase is available as a free download with your MyC-SPAN account. C-SPAN.org offers links to books featured on the C-SPAN networks to make it simpler for viewers to purchase them. C-SPAN has agreements with retailers that share a small percentage of your purchase price with our network. 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There are three ways to set in and out points for a clip: Check your selection with the "Preview Clip" option If you are editing the times of an existing clip, you may only set a start and end time within the original clip boundaries 10:30 am UTC • 33 minI mingle with my peers or no one I am the man who can throw it faster than fuck So that is why I am better than everyone in the world he’s written himself a collection of profane tacky Southern men whose delusions and ineptitude keep them from becoming the heroes they see themselves as in their own minds The approach has allowed him and his tight-knit pack of collaborators to study—and make fun of—a very specific type of 21st-century American unexceptionalism When Kimberly Gregory was cast opposite McBride and Walton Goggins in Vice Principals and an early script called for the HBO show’s two white leads to burn her house down “I want you to know that your character really should be the protagonist She’s the good person,” Gregory recalls him saying Gregory understood McBride’s sense of humor She knew that he knew the truth about his guys: They deserved to be laughed at He’s always trusted his audience to make the same realization “I feel like there’s a knee-jerk reaction to what we do,” McBride says they understand a little bit more of what we’re trying to do and what to expect from it.”  Tae kwon do instructor Fred Simmons in The Foot Fist Way washed-up major leaguer Kenny Powers in Eastbound & Down doofus drug dealer Red in Pineapple Express authoritarian educator Neal Gamby in Vice Principals and rich failson pastor Jesse in The Righteous Gemstones are all pathetically self-important McBride manages to make them at least semi-sympathetic “I don’t think anyone can play characters that make so many mistakes that you want to kick but also hug at the same time better than Danny McBride,” says filmmaker Stephanie Laing who worked on Eastbound & Down and Vice Principals It’s a trick that seems to come naturally to comedy’s preeminent cinephile And with The Righteous Gemstones coming to an end on Sunday after four seasons it’s the perfect time to learn how the hell he does it “Danny’s a very smart man who plays not so smart characters really and so it lulls you into this false sense of camaraderie,” Gregory says that’s my friend down the street—or my not friend down the street.’ It masquerades in a really wonderful way because he’s that good.”Underneath the laughs the Danny McBride oeuvre can be read as one collective cautionary tale: If you start to identify with his characters too much On-screen, McBride always seems to be gleefully running back and forth between highbrow and lowbrow. One scene might reference a François Truffaut film. Another might feature Kenny Powers smelling his baby son’s diaper, holding him up, and asking him this: “What did you eat, diarrhea?” Being part of that wacked-out world is he’s just a force of nature.Craig Robinson (Reg Mackworthy Eastbound & Down): He has this playful confidence but they seeing if you get the joke?Walton Goggins (Lee Russell The Righteous Gemstones): He is one of the kindest people I’ve ever met One of the most well-read people I’ve ever met He’s one of the smartest people I’ve ever met which ultimately has made him literally the funniest person I’ve ever met The Righteous Gemstones): There’s something about him that stays very pure about “I need to gut-laugh about this,” and that’s where the good stuff is Put that out front and figure out the other stuff later.David Gordon Green (consulting producer and director Eastbound & Down; executive producer and director Vice Principals and The Righteous Gemstones): Think about when Fargo came out And you’re in the audience trying to awkwardly figure out if you’re supposed to be laughing at the stuff you’re laughing at When Steve Buscemi gets shot and it’s disgusting or when they’re putting a leg in the wood chipper That’s a great part of what Danny knows how to do Eastbound & Down and Vice Principals; executive producer and director The Righteous Gemstones): Danny has this God-given ability to make you laugh when he does these fucked-up things I don’t think everybody can do that.McBride (cocreator and The Righteous Gemstones): Sometimes we embrace things that are off-putting on purpose I started Lincoln in the Bardo and was just so deeply emotionally impacted But it’s the underlying message of “Maybe this is what happens in the afterlife.” what does he know about the economic differences between Ross and Bloomingdale’s?”Green: He’s very dialed into what’s going on in the world and culture And I say this not jokingly: He’s got a significant diet of reality television he knows the lingo and behavior of what’s happening in technology and I’m still stuck in the mid-’90s.McBride: I think that our sensibilities are very specific.Edi Patterson (Jen Abbott The Righteous Gemstones): I like what my brain does when it’s looking at his brain I feel like cool things happen.Little: We were filming in Puerto Rico and Deep Roy’s mustache is starting to come off He could have made the choice to be stressed and say This is a disaster.” And he made the choice to just go with it McBride: I look back on all these things that we’ve done with HBO there is nothing better than days showing up on that set and being there with Steve Little and us just getting to fucking rip on each other And the same with Walton on Vice Principals and the same on Gemstones with Devine and Edi I think the pleasure that I take from it is just this idea of we’ve created this world and then we get to show up at work and fuck with each other Growing up in the ’80s and early ’90s in Fredericksburg a town off Route 95 about 50 miles south of Washington At the University of North Carolina School of the Arts he met a group of guys with similar tastes McBride: I can remember clearly to this day when our family finally got a VCR I think we were about two years behind everyone else That feeling of going to the fucking video store and suddenly being able to rent movies What you used to only get to see in a theater you could see in your house as many times as you wanted And I just was obsessed.You went to the video store and you didn’t have an understanding of what all these movies were it would be any of the action movies and comedies It was all just trying to rent the most fucked-up-looking movie based on the box.Stuff that I go back to even to this day that I loved when I was a kid: The Shining was my favorite horror movie of all time I loved Ferris Bueller’s Day Off when I was a kid Green: Me and Danny and Jody Hill were all on the same floor Green: Of course the judgments of film school you just want to know what everybody’s VHS collection is And I was just really excited because we had a lot of overlap in the diversity of our collections from absurdist comedies to popcorn and cotton candy blockbusters to weirdo international art films And it was just cool to see someone with an eclectic taste that matched my own And we quickly just realized that we had a similar sensibility for dark comedy and emotional comedy and awkward comedy and that was kind of what our initial creative connection was all about Danny McBride on the Premiere of ‘The Righteous Gemstones’ S4 and I remember thinking that that was unique I hadn’t met anybody like that.Green: He was a big John Hughes fan—so was I—and always had an affection for shit-kicker movies Smokey and the Bandit and Every Which Way but Loose And those were always fun movies to bond on It would be everything from Never Cry Wolf to Scarecrow to Bad News Bears to Sixteen Candles to Predator to Halloween It’s pretty hard to define what our taste is because the only thing that they all have in common is they’re just good fucking movies.McBride: Growing up and living in a little town like Fredericksburg and just renting these movies but I just imagined what it must be like to make that stuff There are all these people working together all these directors.Green: On my first movie he replaced an actor that had bailed—I think it was his first acting gig outside of film school It was really fun to see him go from kind of a writing collaborator to an in-front-of-the-camera incredible performer.Hill: I grew up doing tae kwon do and I owned a school when I was in high school that taught kids and adults It just seemed really funny that Danny would be a tae kwon do instructor.McBride: I took karate as a kid It is also silly and just feels like the perfect mashup for the kind of shit we like Starring McBride, directed by Hill, and cowritten by their late creative partner, Ben Best, The Foot Fist Way was shot in North Carolina over 19 days in 2005 on a reported budget of around $70,000 The brutally uncomfortable comedy introduced its mustachioed lead to the world and caught the attention of two comedy kingmakers Hill: Where we shot was actually the school that I started and the guy that I turned the school over to still owned it and operated it so they let us shoot and use all the kids for free.McBride: Foot Fist got into Sundance into the midnight screening.Hill: Danny had done All the Real Girls but he didn’t have as much of a pop after that but it’s not like everybody in Hollywood knew who he was we had CAA calling us and people in Hollywood wanting to meet Scott Rudin called me on the plane ride to Sundance before we’d even gotten there.McBride: We didn’t get it sold there Green: I’m really proud of Jody for putting it together I’d done film festivals and had that kind of circuit but he was getting phone calls from Ben Stiller and Will Ferrell and Adam McKay McBride: We got hooked up with Will and Adam.Adam McKay (in 2008): I was handed it by Jimmy Miller, our manager, and I watched it in my living room, on the computer, by myself, like on a Saturday afternoon, like, “Ugh, I have to watch this.” And then right away, I was like, “Holy crap.”Will Ferrell (in 2008): I was watching it while working on Blades of Glory in Montreal “This is one of the funniest things we’ve ever seen.”  I couldn’t eat for three days just because I was so nervous about it I didn’t have any point of reference or know how to do it And the thing in Hollywood is you have to pretend like you know what you’re doing because if anyone figures out that you don’t So there was just a sense of you just have to rise to the occasion and do it Green: There was an awakening of a new comic voice I kind of had one foot in the industry from where I was living in North Carolina at the time Judd Apatow and Seth Rogen were one of those And then that led to Pineapple Express for me because he had introduced them to the idea of me wanting to do comedy films And this was before Eastbound—I hadn’t done anything comedic to speak of.McBride: When we came on that scene and met Seth and Evan [Goldberg] and Judd and all these guys it really felt to me and Jody that we had met dudes that we were simpatico with These guys were all a tight-knit group of people that had been dedicating their lives to being creative at a young age And we were doing the same thing clear across the country So the moment that we got to combine forces with them it just felt like the world was opening up in an interesting way of there’s other guys out there like us.”Robinson: We were shooting Pineapple Express “Who is this motherfucker?” Because he was just firing This dude is incredible.”McBride: Those sets were fun You take it for granted because you’re in the middle of it There’s a time where it’s just all Westerns or musicals or now superhero movies And I just think we were really lucky that what we wanted to do happened to align with when all that stuff was what audiences wanted to see Green: That wasn’t like a movie where we were getting studio notes one time one of the executives brought their parents to set and turned right back around and I would ruin takes because I’d keep laughing so hard and had to escort myself off set so that they could finish the scene What that film looks like is what it was to make It was just breaking shit and being almost irresponsible and we were just praying that other people would enjoy that ride McBride appeared in box office smash comedies Superbad he and his buddies started to develop a project of their own: Eastbound & Down McKay and Ferrell executive-produced the series which premiered in early 2009 and gave us Kenny Powers the MLB relief pitcher turned gym teacher with the filthiest mouth in the South the HBO show was both laugh-out-loud funny and somehow moving McBride: I’d always been enamored with British television and I just felt like it was a little bit more interesting I liked the comfort of things like Cheers and The Cosby Show and all these things that I grew up on but I didn’t look at it as the same thing I was trying to do from Alan Partridge to the original Office and Edgar Wright and Simon Pegg’s Spaced—I loved that “What do you want to do next?” That’s what I pitched: our version of a British television show I remember they were surprised by it because people would make TV shows to get movies made I wanted to make something that’s only six episodes long Green: There were a lot of things that people thought were strange about that show I think it took a little bit of reassurance from people like us that we see Kenny Powers in a lot of people we grew up with.Hill: These were the people that either made our lives hell or we made fun of back in the day It was an environment where even the prop person felt empowered to come up with an idea Robinson: You felt like you could improvise, and then you would hit something and then it would catch on, and then you’d figure out how to tag it and call back to it. The big motorcycle fight when Danny’s on the Jet Ski in the lake and it runs out of gas to step off of it as though he might walk on water And it’s one of the best moments in TV because you’re like “Does Kenny Powers really think he can walk on water?”Green: What I like is that your connection to that show depends on your perspective of yourself and culture and mankind That show can appeal to some really despicable characters that say “This guy’s just like me.” Or appeal to a college professor at an Ivy League school that says “This is what makes mankind tick.”Laing: I would take my son to T-ball “My husband loves your show.”Goggins: The thing that I responded to in his work was what lies underneath the comedy I laughed like everybody else in the first season of Eastbound & Down when he pulls out of that gas station and he leaves [April] standing there this is really a romantic comedy.” It’s just disguised.McBride: With every season of it we were never really sure whether we were going to get to do it again And so we really just tried to make every season stand on its own had come to me about halfway through shooting Eastbound having this larger-than-life summation of what it all adds up to for him in his brain His idea of the happy ending is that his wife gets smoked and he starts a new life and he dies and his sidekick snorts his fucking ashes With Eastbound & Down’s four-season run winding down, McBride turned to acting in Hollywood movies like This Is the End and Alien: Covenant. He also developed a second show for HBO. Vice Principals premiered in 2016, a year before he and his pals moved their production company, Rough House Pictures, from Los Angeles to Charleston McBride: You don’t want to fall for the sophomore slump it goes on for years and years and years—years when I was wanting to take more of the approach of filmmakers not wanting to just get narrowed into one thing I learned enough that when you’re writing for television but you also have to give the promise of what comes next And I didn’t want to approach Vice Principals that way I wanted to think of Vice Principals as its own complete story.Laing: He started directing even though it was still very centralized on those two characters.Goggins: I read for Eastbound & Down walked into a room with five comedians there “What the fuck am I doing here?” But I went in and I knew that in my heart I’m such a fan of Danny’s whether he wants it or not.” And it was a great read And I think I said as much to him in the room “I think you need me.” Something stupid like that I got a phone call from David Gordon Green and we don’t know that we want to go that way for this.” And so Jason wound up doing it.And then we were at a party and I really want you to do it.” And it was Vice Principals Like everybody else who reads a Danny McBride script And then the very first table read we did at HBO this guy is going to be very important in my life.” Patterson: When I went to that audition, I had no idea that Danny and Jody were going to be there. I just thought I was going to the casting office to read with Sherry Thomas hi.” And then I just assumed Danny would read with me because that’s who the scenes were with Just go for it.” And so I was throwing some things in It was such a crazy scene—I’m literally coming up from blowing him in a broom closet.Gregory: I had a good friend she has this really eclectic kind of humor I think I’m getting ready to audition for this dude that you’ve been talking about for a long time,” and she went bananas And so I watched a little bit of Eastbound & Down I don’t know if he’s my cup of tea.”So I go into this audition and I could hear all of this laughter and all of this stuff going on and I had no idea that Danny and Jody were in the room this dude is maybe not my dude.” But it was the opposite I’m going to have a good night’s sleep.”Gregory: I didn’t really struggle in the process until I had to do the scene where I had to get drunk and do what I did on the car I can’t do this.” Jody was so almost deferential to me in the process just do whatever.” And he would call me Ms and all of this stuff was wonderful.I think they respected that “Hey she’ll throw in what she can.” All of these respectability politics started coming up in my head What are Black people going to think about me being drunk on what is ostensibly a white male show And this is before we are having these kinds of conversations that we’ve been having in the last eight My father’s family is from Louisiana and Port Arthur “She’s on tonight.” I remember calling either Jody or Danny Do we have to do it?” And I think it was Danny who was like I was angry in that scene when I’m walking down the street knocking people’s drinks over but I had become very childish and infantile “You’re making me do something I don’t want to do.” But when I was at this theater leadership night and this woman came up to me and was like “My wife just told me that you’re the actress We love this show.” And it was a Black woman it just really makes me happy that all of the stuff I was afraid of was not real And my community in particular really wrapped their arms around Belinda even though she was being battered in the show in some ways That was the only moment where I just felt like Goggins: No one can ruin a take quicker than me I think Danny’s gone on record as saying that because I find him as funny as I find Bill Murray Literally just looking at him walk in a room But there was this one line on Vice Principals And I’m going to say we drove around Charleston 25 minutes trying to get this one line in a take where one of us didn’t laugh and we were so lucky to do back-to-back seasons and kayak off of our little houses in Charleston such a wise decision.McBride: I was always enamored with what that world must be like and it wasn’t as cool as I thought it was going to be.Mixon Greer: I think whenever you’re filming elsewhere it’s always a special situation.Devine: The sense of community that we have in Charleston everyone just loves being there and loves working with each other And it’s the same people that work on all of [Danny’s] stuff all the time He immediately had his whole crew.Laing: What a gift to be able to live and work in a space that’s inspiring to you where you don’t feel like you have to be in Hollywood I think they’ve set something up that’s so enviable It just allows them to continue to tell stories the way that they want to tell them.McBride: Vice Principals was a way to say let’s just focus on telling one story in this format and then be done with it.” And it was that thing where when I finished it I had such a fucking good time shooting that and working with all those actors that were in it that there was this moment of panic of maybe I should have planned this to be a longer series.” But the magic that we captured was in that moment in time After Vice Principals, McBride and his crew started branching out beyond comedy. Their Halloween reboot, which Green directed and cowrote with McBride and their college friend Jeff Fradley, hit theaters in October 2018 and grossed almost $260 million worldwide The movie’s two sequels each made more than $100 million Green: I got a call one day from Jason Blum asking if I’d be interested in talking about rebooting the Halloween franchise with John Carpenter involved And I just got super excited and butterflies in my stomach and called up Danny and said “You won’t believe the conversation I just had.”McBride: My first reaction was like Everyone will hate you.” But then the more we talked about it I think that we have an interesting way into this.”Green: He says That would be a childhood dream.” I remember driving to the Blumhouse office with Danny I think it was at a time in his life when he was drinking 5-Hour Energy drinks The two of us were talking to Jason and then he says Let’s go sit with John Carpenter.”McBride: I can remember to this day walking into John Carpenter's house And once we saw that Jamie Lee [Curtis] was interested it became hard not to get excited about the potential of it.Green: The snowball of creative nostalgic passions that we were able to unleash on that franchise was incredible And it’s one thing to be able to have these opportunities solo But when you get to bring your college buddy and you’re side by side taking the hits and feeling the wins on this ride together McBride: When we premiered that first one at TIFF and I’ve been mad at things being relaunched before and hated on them now’s my chance to be in the fucking bull’s-eye.” But man when we watched that thing with that crowd and then the first time that Jamie goes over the balcony and Michael looks over and she’s gone and it gets into that last cat and mouse in the house I can come back alive.” It’s one of the best feelings I’ve ever had with any audience “All these rich-people-on-compound shows.” Since then the dramatic comedy has become ridiculously ambitious pulling off everything from motorcycle chases to a pro wrestling period piece to jet pack sermons to the premiere of the fourth and final season a gory Civil War–set flashback starring Bradley Cooper as the first Gemstone preacher.McBride: Gemstones ended up being something where we defied any sort of genre rules Goggins: When I’ve read anything that Danny has done But they’re so three-dimensional that the work required to inhabit them isn’t a lot really.Patterson: I just think he goes straight toward what he thinks is funny and good and is able somehow to not get bogged down in “Yeah but this is a real type of person that has made me laugh before so why don’t we dive in deep?”Laing: It’s almost like sitting in an airport waiting for your flight and you see the most interesting people walk by and you just wonder what their lives are.Tony Cavalero (Keefe Chambers The Righteous Gemstones): I remember people would be like Is he literally a gas station attendant in your cast?”Devine: Danny called me and was like “Would you be interested in playing my brother?” And I was like I think I can make that work.” We met once and he’s on my Mount Rushmore of comedy.And I said to him “You’re a bright shooting star.” And he goes And I went and grabbed my girlfriend at the time “I just called Danny McBride a bright shooting star.” And she’s like You want me to play your 70-year-old uncle he can’t do that.” And so we had to do a camera test he could absolutely do that.”Devine: When you show up on Danny’s set “I’m going to fucking bring it because I want these guys to love what I do.” I mean Laing: There’s just such a specificity in the way he embodies his characters his mannerisms—it’s like there’s no one like him.Patterson: There’s a vibe thing that happens when he’s in the Cape and Pistol stuff and it’s a haughtiness of trying to be the boss and trying to be cocky but at the same time looking so dumb and twirling your cape There’s something in that overconfidence that I think is the sweet spot for him and kills me Gregory: I’ve seen Danny with and around his family, and that is something that speaks more than what I see someone doing on their set. A really gentle, fatherly sci-fi world would be really interesting to see Danny in. Danny has a good-soul-ness to him, and I would love to see him play something where that kind of shines through.McBride: There’s so much. Just wait and see.Green: Inside the absurdist comic voice is an intellectual with great mythological understanding.  McBride: I grew up in the ’80s, and martial arts was something that you definitely saw in the movies, and it seemed like a good skill to have—to be able to beat somebody’s ass, to be able to take a bad guy out. It hearkens back to an age when life was simpler. A good roundhouse kick could solve all your problems. WASHINGTON − The Supreme Court's conservatives argued religious institutions can’t be treated as second-class and railed against discrimination Concerns about opening the door to public funding for religious charter schools of all faiths "reeks of hostility," one said More: Amy Coney Barrett recused herself from big religious charter school Supreme Court case Its liberal justices defended the country’s longstanding separation between church and state as the court debated on April 30 whether to allow the nation’s first religious charter school One justice stated that a win for the religious charter could jeopardize the quality of a publicly funded education nationwide Attorneys for the Catholic Church, an Oklahoma charter school board and the Justice Department told the Supreme Court that allowing St Isidore of Seville Catholic Virtual School was the natural next step following a series of recent decisions from the court who defended the state supreme court's ruling rejecting the Catholic charter pointed to landmark rulings against teaching religion in public schools Requiring Oklahoma to allow religious schools in its charter school program would be an “astounding reversal from this court's time-honored precedents.” More: How Oklahoma leaders at Supreme Court hearing on religious charter school responded to arguments The Catholic Church's appeal is just one of three religious rights cases the Supreme Court is deciding in the coming weeks that could increase the role of religion in public life Here are key moments from the oral arguments The court’s decision is expected to turn on whether charter schools which are publicly funded but have private operators the justices could rule that religious charter schools violate the Constitution’s prohibition on the government backing a religion the government could be discriminating when it prohibits the church from participating in the state’s charter school program The justices could find that's a violation of the U.S Constitution’s promise that Americans can practice religion freely Justice Sonia Sotomayor said charter schools are public because they’re funded by the taxpayers Justice Elena Kagan called them “state-run institutions.” “They give the charter schools a great deal of curricular flexibility,” she said “But with respect to a whole variety of things the state is running these schools and insisting upon certain requirements." He said the only way the school would receive public funds would be if parents chose to send their children there said Oklahoma is just “exercising contractual oversight.” “The state is not running these schools,” Campbell said suggested that Oklahoma was treating religious schools "as second class in the United States." "That seems like rank discrimination against religion and that's the concern that I think you need to deal with here," Kavanaugh told Garre accusing the Oklahoma attorney general's office of being "motivated by hostility toward particular religions." He quoted the attorney general as saying many Oklahomans likely support charter schools for Christian faiths but that support would require the state to approve similar schools from all faiths "We have statement after statement by the attorney general that reeks of hostility toward Islam," Alito said "If your concern is the treatment of Islam or Muslims then the concern should be the Muslim family whose only practical option is the religious charter school that happens to teach the Catholic faith as truth," Garre said all three liberal justices expressed skepticism toward the Catholic school's position Isidore were forgetting a provision in the Constitution that prohibits the government from establishing an official religion/ "The essence of the establishment clause was 'We're not going to pay religious leaders to teach their religion,'" Sotomayor said said a win for the Catholic school could mean having to provide taxpayer dollars for schools that aren't providing a strong education in areas like math and reading “I don’t have to imagine very hard to come up with 100 hypotheticals like this because religious communities are really different in this country and are often extremely different from secular communities in terms of the education they think is important for their young people," Kagan said Chief Justice John Roberts appears to be a pivotal vote which would mean the Oklahoma Supreme Court's ruling against the Catholic school would stand Roberts said early in the arguments that previous rulings from him and his colleagues did not clearly indicate the Catholic school should win even if those decisions expanded religious protections a lawyer for the charter school board that approved the Catholic school what past ruling would support the level of government mixing with a religious school that the Catholic school and board were now requesting that his argument for why charter schools are public didn't seem to square with the court's past decisions Roberts asked how extensively the state could require charter schools to teach certain subjects said if there were a requirement to teach evolution and a school rejected it The state has a compelling interest that evolution be taught Kagan suggested mainstream religions could meet the state’s requirements But more obscure ones might have trouble if the government curriculum violated religious schools' beliefs “There’s a line out the door” of people seeking charter funding “We’re going to end up in a state of the world with kind of establishment religions and more different more use-the-adjective-you-want religions that seem peculiar to many eyes Sauer said allowing religious charter schools would only increase options for where parents could send their children that line out the door will increase the diversity of options for parents and students that have programs that are similar to Oklahoma,” Sauer said Could students be forced to attend religious schools?Alito who is aligned with his conservative colleagues questioned how religious charter schools could become the only option for students in some areas one of the criticisms that have been lodged against them the only public schools are charter schools who was defending the state supreme court's position Half the public schools are charter schools in other places there are jurisdictions where children are assigned to charter schools by default I don’t want to go to the Catholic charter school,’” he said “That raises the same problem as raising your hand in the public school and saying you don’t want to participate in prayer today.” argued that "the mere specter that that might result in the future is not a reason to categorically exclude religious groups on the front end." Lawyers for the state and federal governments disagreed about the implications of the high court allowing religious charter schools said states that don’t want to allow religious private schools could restructure their programs said every charter school law in more than 40 states would become unconstitutional because they all require charter schools to be public and nonsectarian Some states might change their laws to adapt and ramp up charter schools but others would abandon charter schools to avoid teaching religion confusion and disruption for potentially millions of school children and families across the country,” Garre said The court would also be putting itself in a position to judge future cases about whether charter schools could exclude gay teachers or teach creationism rather than evolution “There is going to be a lot of line drawing,” Garre said Most oral health conditions are largely preventable and can be treated in their early stages Most cases are dental caries (tooth decay) Other oral conditions of public health importance are orofacial clefts noma (severe gangrenous disease starting in the mouth mostly affecting children) and oro-dental trauma Prevalence of the main oral diseases continues to increase globally with growing urbanization and changes in living conditions This is primarily due to inadequate exposure to fluoride (in the water supply and oral hygiene products such as toothpaste) availability and affordability of food with high sugar content and poor access to oral health care services in the community Marketing of food and beverages high in sugar have led to a growing consumption of products that contribute to oral health conditions and other NCDs Dental caries results when plaque forms on the surface of a tooth and converts the free sugars (all sugars added to foods by the manufacturer syrups and fruit juices) contained in foods and drinks into acids that destroy the tooth over time inadequate exposure to fluoride and a lack of removal of plaque by toothbrushing can lead to caries pain and sometimes tooth loss and infection Periodontal disease affects the tissues that both surround and support the teeth The disease is characterized by bleeding or swollen gums (gingivitis) the gum can come away from the tooth and supporting bone causing teeth to become loose and sometimes fall out Severe periodontal diseases are estimated to affect more than 1 billion cases worldwide The main risk factors for periodontal disease are poor oral hygiene and tobacco use Losing teeth is generally the end point of a lifelong history of oral disease mainly advanced dental caries and severe periodontal disease but can also be due to trauma and other causes The estimated global average prevalence of complete tooth loss is almost 7% among people aged 20 years or older a much higher global prevalence of 23% has been estimated Losing teeth can be psychologically traumatic socially damaging and functionally limiting other parts of the mouth and the oropharynx and combined rank as the 13th most common cancer worldwide The global incidence of cancers of the lip and oral cavity is estimated to be 389 846 new cases and 188 438 deaths in 2022 (1) Oral cancer is more common in men and in older people more deadly in men compared to women and it varies strongly by socio-economic circumstances alcohol and areca nut (betel quid) use are among the leading causes of oral cancer human papillomavirus infections are responsible for a growing percentage of oral cancers among young people Oro-dental trauma results from injury to the teeth Latest estimates show that 1 billion people are affected with a prevalence of around 20% for children up to 12 years old Oro-dental trauma can be caused by oral factors such as lack of alignment of teeth and environmental factors (such as unsafe playgrounds Treatment is costly and lengthy and sometimes can even lead to tooth loss resulting in complications for facial and psychological development and quality of life Noma is a severe gangrenous disease of the mouth and the face It mostly affects children aged 2–6 years suffering from malnutrition living in extreme poverty with poor oral hygiene or with weakened immune systems Noma is mostly found in sub-Saharan Africa although cases have also been reported in Latin America and Asia Noma starts as a soft tissue lesion (a sore) of the gums It then develops into an acute necrotizing gingivitis that progresses rapidly destroying the soft tissues and further progressing to involve the hard tissues and skin of the face According to latest estimates (from 1998) there are 140 000 new cases of noma annually Survivors suffer from severe facial disfigurement and require complex surgery and rehabilitation its progression can be rapidly halted through basic hygiene the most common of craniofacial birth defects have a global prevalence of between 1 in 1000–1500 births with wide variation in different studies and populations (2) alcohol and obesity during pregnancy also play a role there is a high mortality rate in the neonatal period If lip and palate clefts are properly treated by surgery Most oral diseases and conditions share modifiable risk factors such as tobacco use alcohol consumption and an unhealthy diet high in free sugars that are common to other NCDs including cardiovascular disease diabetes has been linked in a reciprocal way with the development and progression of periodontal disease There is also a causal link between the high consumption of sugar and diabetes Oral diseases disproportionately affect the poor and socially disadvantaged members of society There is a very strong and consistent association between socioeconomic status (income occupation and educational level) and the prevalence and severity of oral diseases This association exists from early childhood to older age and across populations in high- The burden of oral diseases and other noncommunicable diseases can be reduced through public health interventions by addressing common risk factors Adequate exposure to fluoride is an essential factor in the prevention of dental caries Twice-daily tooth brushing with fluoride-containing toothpaste (1000 to 1500 ppm) should be encouraged Unequal distribution of oral health professionals and a lack of appropriate health facilities to meet population needs in most countries means that access to primary oral health services is often low Out-of-pocket costs for oral health care can be major barriers to accessing care Paying for necessary oral health care is among the leading reasons for catastrophic health expenditures resulting in an increased risk of impoverishment and economic hardship.  The World Health Assembly approved a Resolution on oral health in 2021 at the Seventy-fourth World Health Assembly The Resolution recommends a shift from the traditional curative approach towards a preventive approach that includes promotion of oral health within the family comprehensive and inclusive care within the primary health-care system The Resolution affirms that oral health should be firmly embedded within the NCD agenda and that oral health-care interventions should be included in national universal health coverage benefit packages In response to the mandate outlined in the resolution, the Secretariat developed the Global strategy on oral health and included the Global oral health action plan 2023‒2030 (GOHAP) in the report on NCDs noted by the Seventy-sixth World Health Assembly in 2023 (WHA76.9). The GOHAP includes a range of actions for Member States civil society organizations and the private sector In 2024, as an outcome of the first ever WHO Global Oral Health Meeting that took place 26–29 November in Bangkok, Thailand, the Bangkok Declaration – No Health Without Oral Health was adopted This Declaration advocates for elevating oral diseases as a global public health priority The Bangkok Declaration reiterates Member States' commitment to the landmark 2021 resolution on oral health which advances the prevention and control of oral diseases as part of the NCD It emphasizes the need to strengthen health systems through primary health care approaches ensuring that environmental sustainability and climate resilience are central components France: International Agency for Research on Cancer Available from: https://gco.iarc.who.int/today cleft lip and cleft palate and lip: A comprehensive systematic review and meta-analysis The World Health Assembly approved a Resolution on oral health in 2021 at the Seventy-fourth World Health Assembly In response to the mandate outlined in the resolution, the Secretariat developed the Global strategy on oral health In 2024, as an outcome of the first ever WHO Global Oral Health Meeting that took place 26–29 November in Bangkok, Thailand, the Bangkok Declaration – No Health Without Oral Health was adopted This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Please enable JS and disable any ad blocker Amid the growing macro-level headwinds in the vaccine space the FDA this month is expected to decide on Moderna’s mRNA COVID-19 shot GSK is proposing its subcutaneous biologic Nucala to treat adult patients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype. The FDA’s decision is due on May 7 A pulmonary disease, COPD is characterized by inflammation in the lungs, manifesting as breathlessness, coughs and airflow obstruction. According to GSK, some 40% of patients suffer from disease exacerbations caused by type 2 inflammation, which in turn is linked to high eosinophil counts in the blood. Nucala which is crucial to maintain the activity of eosinophils GSK is supporting Nucala’s COPD application with data from the Phase III MATINEE trial. The pharma released a topline readout from the study in September 2024 noting that Nucala elicited a “statistically significant and clinically meaningful reduction” in yearly rates of moderate or severe disease exacerbations as opposed to placebo Nucala is currently approved for eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome and as an add-on maintenance treatment for asthma and chronic rhinosinusitis with nasal polyps By May 22, the FDA will release its verdict on Arcutis Biotherapeutics’ proposed expansion for Zoryve into body and scalp psoriasis Arcutis is backing its expansion bid with data from the Phase III ARRECTOR trial which found that 66.4% of Zoryve-treated patients achieved clear or almost-clear skin Results also showed that 65.3% of patients in the Zoryve arm saw significant improvements in itch Arcutis also filed findings from a Phase IIb study as well as long-term efficacy and safety data for Zoryve in plaque psoriasis Zoryve is a topical phosphodiesterase 4 inhibitor that works by helping to suppress inflammation in the skin The drug won FDA approval in 2011 for the treatment of plaque psoriasis in patients aged 12 years and up Zoryve would be a “truly meaningful innovation” for patients who suffer from inadequately controlled symptoms Arcutis CEO Frank Watanabe said in a September 2024 release Sanofi’s meningococcal disease vaccine MenQuadfi is currently approved for the primary immunization of children aged two years and up it can be used in those 13 years and older who continue to be at risk of meningococcal disease Sanofi is seeking to expand MenQuadfi’s label to also include infants and toddlers from six weeks to 23 months of age. The FDA is currently reviewing this proposal and is due to release its decision on May 23 MenQuadfi could protect this younger population from the A W and Y serogroups of Neisseria meningitidis In an April presentation before the CDC’s Advisory Committee for Immunization Practices Results showed that MenQuadfi was safe to use in infants and toddlers with most side effects being mild or moderate in severity MenQuadfi was able to match a commercially approved vaccine in immune response and seroprotection On May 23, Liquidia is expecting to win final approval of its inhalation powder Yutrepia for the treatment of patients with pulmonary arterial hypertension associated with interstitial lung disease (PH-ILD) The FDA gave the drug tentative approval in August 2024 indicating that it had cleared all efficacy and safety hurdles and satisfied regulatory standards of product quality Liquidia still needed to wait out regulatory exclusivity for a competing product Merck is hoping to expand its oral cancer drug Welireg into advanced pheochromocytoma and paraganglioma (PPGL). The FDA’s decision deadline is May 26 PPGL refers to two types of rare tumors of the adrenal gland. Diagnosed in some 2,000 patients per year, they are typically caused by specific genetic mutations. Symptoms include high blood pressure up to 25% of PPGL cases are already at the metastatic stage at diagnosis Merck is supporting Welireg’s PPGL bid with data from Cohort A1 of the Phase II LITESPARK-015 study. The pharma did not provide specific data in a January news release revealing only that the application is based on objective response rate and duration of response in PPGL patients after Welireg treatment The FDA has granted the drug priority review in this indication Welireg is an orally available inhibitor of the HIF-2α transcription factor which is involved in oxygen sensing and in the body’s response to hypoxia The drug is indicated for patients with renal cell carcinoma (RCC) and those with von Hippel-Lindau disease—a rare genetic disease involving the formation of tumors across various organs—who also require treatment for associated RCC Welireg will become the only drug for advanced PPGL in the U.S. By May 28, the FDA will release its verdict on Eton Pharmaceuticals’ ET-400 for the treatment of adrenal insufficiency in infants This new target action date comes after the FDA in February announced that it needed more time to review Eton’s data package for ET-400 Eton submitted supplemental information in December last year in response to a request from the regulator is designed to rapidly deliver glucocorticoids to children with adrenocortical insufficiency In a July 2024 announcement Eton CEO Sean Brynjelsen said that the approval of ET-400 would allow the biotech to “capture a greater percentage of the oral hydrocortisone market” and would open up a peak opportunity of “more than $50 million annually.” The FDA’s last big milestone for the month belongs to Moderna and its investigational next-generation COVID-19 vaccine mRNA-1283. The regulator is expected to release its decision on May 31 the company released Phase III data for the experimental shot only claiming that mRNA-1283 elicited a “higher immune response” against SARS-CoV-2 than Spikevax Moderna emphasized at the time that mRNA-1283 could induce robust responses against Omicron and original strains of the virus—a benefit the company claimed was most evident in seniors over 65 years of age Oral Health CoalitionPRAMSTobacco Quitline Having trouble finding what you are looking for? Use our A to Z Index The Oral Health Branch is dedicated to preventing dental disease for Alabama's citizens by promoting and developing quality cost-effective community and school-based preventive and early treatment programs that emphasize the elimination of oral health disparities Oral Health is an essential and integral component of health throughout life No one can be truly healthy unless he or she is free from the burden of oral diseases and conditions Millions of people in the United States experience dental caries and periodontal disease resulting in needless pain and suffering The Oral Health Branch has developed the following materials to help educate Alabamians on the benefits of healthy teeth and gums The Alabama Department of Public Health (ADPH) is excited to announce the winners of our eighth annual “Share Your Smile with Alabama” statewide photo contest: Channing Rose Coghlan from Lowndes County who attends Fort Dale Academy in Butler County Visit Share Your Smile with Alabama for details Introducing Alabama's first Burden of Oral Disease document This comprehensive oral health disease burden report serves as a critical tool in evaluating the state's dental landscape The full report is available to download below The Oral Health Branch accomplishes its mission through several programs. These include oral health education programs and materials, community water fluoridation, and the dental screening program Oral health data from various sources are available that characterize the oral health of Alabama's children and adults Finally, information is available on locating a dentist throughout the state and other dental provider lists are also available Call (334) 206-2924 or contact us via email to obtain further information Already have an account? Log in here Supreme Court heard oral arguments Wednesday over the nation’s first religious charter school that aims to open in Oklahoma putting the constitutionality of a state-funded Catholic education to the test An Oklahoma state board approved St. Isidore of Seville Catholic Virtual School to operate as a publicly funded charter school in 2023. The Oklahoma Supreme Court blocked the school from opening in a June ruling finding the concept of a religious charter school a violation of the Constitution’s prohibition against government-established religion a Catholic with ties to two legal groups behind St Students pay about $14 in fees that support the Daily If you're not a student and value our work Five of the eight remaining justices who heard the case also are Catholic — John Roberts and Justice Ketanji Brown Jackson is a nondenominational Protestant A decision from the Court is expected by the end of June Kagan and Jackson — appeared doubtful that previous rulings support the idea that a charter school could constitutionally adopt a religion Kagan also wondered about the nationwide implications of permitting publicly funded religious schools said disapproving a charter school solely on religious grounds “seems like rank discrimination against religion.” Opening charter school funding to faith-based institutions would “be expanding the options not contracting the options” of school choice in public education ‘Don’t exclude us based on religion,’” Kavanaugh said Isidore’s founding contract differs from that of other charter schools The school pledged to comply with state regulations and non-discrimination laws only to the extent that Catholic doctrine allows The Court made prior decisions that religious schools can’t be excluded from government grants and state-funded tuition assistance programs a religious school wasn’t changing the terms of a government program “It seems to me you are not seeking the same public benefit as everyone else,” Jackson said The Archdiocese of Oklahoma City and the Diocese of Tulsa applied to open St named after the patron saint of the internet to offer an online Catholic education to students in all parts of the state particularly in rural areas with no brick-and-mortar Catholic school Isidore would be Catholic in all ways but open to students of all belief systems Students would have to learn Catholic doctrine and obey school rules inspired by church beliefs Supreme Court heard our case and now entrust it to their wisdom,” Oklahoma City Archbishop Paul S we pray and hope for a decision that stands with religious liberty and the rights of Oklahoma families to make their own decisions in selecting the best educational options for their children.” Both the school and the Oklahoma Statewide Charter School Board Oklahoma’s attorney general has led the legal battle against the school chief legal counsel of the national conservative legal group Alliance Defending Freedom presented the statewide board’s oral arguments Wednesday Both contended charter schools aren’t an arm of the government like traditional public schools they are private entities who contract with the state to provide a public service and therefore should be free to adopt a religion Campbell said he found the justices “very receptive to the arguments we were making.” “The First Amendment says when you create a program and invite everyone in but tell only religious groups that they can’t come gave oral arguments on behalf of the Oklahoma attorney general who said the concept of a publicly funded religious school is unconstitutional Charter schools bear all necessary resemblance to traditional school districts to be considered public The state can open and close a charter school They are subject to the equal academic standards as Oklahoma public schools and most of the same regulations though they have more flexibility over teaching methods and employee hiring though they must contract with a traditional school district Native American tribe or a state board that oversees them as a charter authorizer and federal law all define charter schools as public schools and forbid them from religious affiliation charter schools must comply with church-state separation “When I look at Oklahoma and its charter schools program they look like regular public schools,” she said So why shouldn’t we take the state at its word (that they are public)?” Oklahoma Attorney General Gentner Drummond has been the school’s leading opponent despite it having support from fellow Republican leaders in the state Isidore would create a “slippery slope” leading to charter schools teaching faith systems that most Oklahomans would disagree with — a position Alito said “seems to be based on hostility to certain religions.” Kevin Stitt has been a vocal advocate of opening St Stitt said the school “expands choice and freedom,”  and the government shouldn’t stand in the way “I think the Supreme Court is going to rule with us because it’s just common sense,” he said Charter school advocates feared a ruling in St Isidore’s favor could cause a widespread closure of charter programs in states that won’t abide taxpayer-funded religious education “we won’t know what the rules are for charter schools anymore in 47 states and the federal level,” said Starlee Coleman president and CEO of the National Alliance for Public Charter Schools “This is going to shut down the charter school program in many states where there is simply no appetite by state lawmakers to fund religious schools,” Coleman said after oral arguments Illinois where there are millions of children attending charter schools today.” Oklahoma Voice is an affiliate of States Newsroom, a nation 501(c)(3) nonprofit supported by grants and donations focused on delivering state government news. The Voice maintains full editorial independence. For more stories by Oklahoma Voice go to oklahomavoice.com Students pay about $14 in fees that support the Daily. If you're not a student and value our work, please disable your ad blocker or click here to match that if you can. The Dental Health Program (DHP) at VDH works internally and with partners to make Virginia the healthiest state in the nation by improving equitable access to dental care and public health interventions that improve oral health outcomes The DHP in Virginia began in 1952 with school-based clinical programs VDH employed over 100 dentists and auxiliary staff to provide dental services and education the Agency has re-aligned the DHP’s focus on prevention and education and has transitioned clinic-based restorative programs to community-based prevention programs The ability of VDH dental hygienists to work under “Remote Supervision,” without the direct supervision or initial exam of a dentist has led to the success of the community-based education All 5 Releases Libraries  A-Z Index  Directories The Department of Communication Sciences and Oral Health is made up of two main program areas: Communication Sciences, with Speech-Language Pathology and Education of the Deaf programs, and Dental Hygiene A dental hygiene degree from Texas Woman’s opens up career opportunities to you beyond the dentist office. Our programs teach you critical thinking and evidence-based decision making with a global context you won’t find at other universities. TWU dental hygiene students train in our on-campus Dental Hygiene Clinic to receive hands-on experience with patients MCL 8201314 N. Bell Ave.Denton, TX 76204-5737940-898-2025 (phone)940-898-2070 (fax)coms@twu.edu  MCL 9111314 N. Bell Ave.Denton, TX 76204-5796940-898-2870 (phone)940-898-2869 (fax)dh@twu.edu straightforward answers when I asked patients about their tobacco use “I don’t smoke.” Then later in the appointment they would casually mention using nicotine pouches I saw friends discreetly popping in nicotine pouches with little thought or discussion Nicotine pouches are rapidly gaining popularity Social media platforms are flooded with videos and posts that spread awareness of these products Most of our time in dental hygiene training is spent learning about the effects of traditional tobacco products on the oral cavity it’s time to expand our focus beyond cigarettes and vapes What exactly are nicotine pouches doing to the oral cavity Nicotine pouches are a recent addition to the nicotine product market gaining widespread availability starting in 2019 in Europe smokeless alternatives to traditional tobacco products Each nicotine pouch typically contains between 1.29 mg and 6.11 mg of nicotine although some are now being marketed with levels as high as 11 mg per pouch These pouches are typically made from plant fibers offering individuals an “easy-to-use” form of nicotine delivery.2 Additionally many nicotine pouches include food-grade additives and flavorings such as mint and various fruit flavors aimed at appealing to a wide range of consumers Most of these pouches use artificial sweeteners instead of sugar which may lower the risk of dental caries.3 However the absence of sugar doesn’t eliminate oral health concerns as keeping the pouches in the same spot in the mouth for extended periods can cause localized tissue irritation Unlike traditional smokeless tobacco products these alternatives eliminate the need to spit making them more socially acceptable and attractive for those looking for a cleaner option.4 Marketed as a more convenient and “lower risk” choice with a reduced potential for misuse these products are rapidly gaining popularity among tobacco users and dental professionals should be mindful of this a Swedish nicotine pouch available in nicotine strengths ranging from 3 mg to 8 mg per pouch.2 Users place the pouch between their gum and lip and it gradually releases nicotine into their bloodstream.5 Another brand is On! which offers nicotine strength from 1.5 mg to 8 mg.6 Lastly All three brands offer a wide range of flavors Though nicotine pouches are marketed as a safer alternative to smoking or chewing tobacco they still carry significant risks for oral health.7 One study which compared Zyn nicotine pouches to traditional Swedish and smokeless tobacco products found that even the lower amounts of nicotine in Zyn pouches could deliver nicotine to the bloodstream as effectively as other smokeless products Participants in the study reported mild side effects as dry mouth can increase the risk of tooth decay A case series investigating the effects of nicotine pouches on oral health highlighted the potential for adverse outcomes.8 The study examined five users focusing on oral health and conducting histopathological analyses users developed white lesions in their mouths usually near the upper lip and frenum where the pouches were placed Histopathological analysis revealed inflammation a condition in abnormal growth of cells in tissue These findings suggested that nicotine pouch use can directly impact oral tissues A systematic review of the potential oral health risks of nicotine pouches analyzed three studies involving 190 participants.9 The researchers discovered that frequent use of nicotine pouches was linked to several oral health issues These problems were commonly observed among regular and long-term users The review noted concerns that nicotine pouch use might contribute to inflammation and increase the risk of oral cancer although the evidence was limited and the studies involved had a high risk of bias particularly among adolescents and young adults While current studies highlight oral mucosal changes the full extent of systemic and long-term oral health effects remain unclear especially regarding potential links to oral cancer and chronic tissue damage dental hygienists are essential in identifying early signs of damage caused by new nicotine products ask the right questions during patient assessments and include nicotine pouches in our patient education and tobacco cessation conversations we can empower patients to make more informed choices and potentially prevent long-term damage Tobacco companies introduce 'tobacco-free' nicotine pouches 3. Patwardhan S, Fagerstrom K. The new nicotine pouch category: a tobacco harm reduction tool? Nicotine Tob Res. 2022;24: 623-625. doi:10.1093/ntr/ntab198 Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users https://lucy.co/products/pouchesf?variant=41980094742714&selling_plan=711688378# Pharmacokinetic comparison of a novel non-tobacco-based nicotine pouch (Zyn) with conventional tobacco-based Swedish snus and American moist snuff Correction: oral mucosal changes caused by nicotine pouches: case series What is the impact of nicotine pouches on oral health: a systematic review https://doi.org/10.1186/s12903-024-04598-8 This purchase is available as a free download with your MyC-SPAN account C-SPAN.org offers links to books featured on the C-SPAN networks to make it simpler for viewers to purchase them C-SPAN has agreements with retailers that share a small percentage of your purchase price with our network C-SPAN earns money from your qualifying purchases C-SPAN only receives this revenue if your book purchase is made using the links on this page Any revenue realized from this program goes into a general account to help fund C-SPAN operations Please note that questions regarding fulfillment or issues relating to your book orders should be directed to the Webmaster or administrator of the specific bookseller's site and are their sole responsibility MyC-SPAN users can download four Congressional hearings and proceedings under four hours for free each month If you are editing the times of an existing clip you may only set a start and end time within the original clip boundaries The National Institute for Health and Care Excellence (NICE) has recommended linzagolix (Yselty Theramex) for treating endometriosis in selected patients The decision applies to women for whom previous medical or surgical treatments have not alleviated their symptoms The drug is a gonadotropin-releasing hormone (GnRH) antagonist taken orally allowing patients to self-administer the treatment at home It must be used alongside hormonal add-back therapy to help reduce potential side effects In final draft guidance NICE said there was sufficient evidence to show that linzagolix with hormonal add-back therapy provides clinical benefits and value for money the treatment will be made available on the NHS in England NICE estimated that up to 1000 women a year could benefit from the treatment Endometriosis affects around 1.5 million women in the UK Linzagolix offers a non-injectable alternative to existing options It is already approved for treating moderate to severe symptoms of uterine fibroids The hormonal add-back therapy includes oestradiol 1 mg and norethisterone acetate 0.5 mg to help mitigate potential side effects Current therapeutic options for endometriosis include surgery and relugolix-oestradiol-norethisterone acetate (relugolix combination therapy [CT]) NICE said that clinical trial evidence showed that linzagolix with hormonal add-back therapy demonstrated statistically significant reductions in both dysmenorrhoea and non-menstrual pelvic pain compared with placebo Indirect comparisons suggested that the combination offers similar pain relief to leuprorelin acetate and relugolix CT Relugolix CT became the first long-term pill licensed to treat endometriosis following NICE’s approval for NHS use in March The cost of linzagolix was judged comparable to relugolix CT and considered acceptable against standard care options such as surgery or leuprorelin NICE found that the cost-effectiveness of linzagolix with hormonal add-back therapy to be within its acceptable range described the drug as “a valuable addition to the options available for this often painful and disruptive condition.” She noted the convenience of once-daily dosing at home and its potential to ease pressure on NHS services Linzagolix is supplied as 200-mg film-coated tablets The hormonal add-back therapy costs £13.20 for a pack of 84 tablets Annual treatment costs are estimated at £1100 The most common side effects reported in trials include hot flushes (6.3%) and headache (5.7%) Linzagolix is subject to additional monitoring to allow quick identification of new safety information Treatment should be supervised by a physician experienced in the diagnosis and treatment of endometriosis Final guidance is due to be published on 25 June The NHS in England must make the treatment available within 90 days of publication Sheena Meredith is an established medical writer and consultant in healthcare communications with extensive experience writing for medical professionals and the general public She is qualified in medicine and in law and medical ethics Send comments and news tips to uknewsdesk@medscape.co.uk 2025 8:30 AM EDTMen’s Journal aims to feature only the best products and services.  If you buy something via one of our links Over 1,000 of these toothbrushes have been bought in the past month and they've received around 1,250 five-star ratings for stellar and clearly visible performance as all the others have sold out at this price Oral-B’s ADA-accepted smart toothbrush is designed to give you a great it includes a pressure sensor and position detection system to ensure you hit every tooth surface without pressing so hard to damage your gums It also has a vibrating timer to ensure you brush long enough There are five cleaning modes to choose from and even one made specially for your tongue to maximize mouth health The Oral-B Pro Smart Limited has a battery life of a week or more and comes with a travel case for great oral health on the go One shopper who heavily values dental health referred to this Oral-B toothbrush as “the best investment ever” and compared it positively to Philips' brushes “I’ve tried a Phillips electric toothbrush in the past but it did not provide the cleaning I needed This toothbrush provides a dentist-like cleaning with every brush.” They went on to say they now “have little to no plaque along with regular flossing.” They commented specifically on the positives of the Pro Smart Limited’s handle: “It's got a textured surface that makes it easy to grip and not slip in your hands.” You can get this Oral-B smart toothbrush for its all-time low price on Amazon for just $70 Three of the brush’s four color variations are already sold out and the black version could go at any time Sign up for Men's Journal's Recommended By newsletter to get gear, fitness, and more deals delivered straight to your inbox. Prices are accurate and items in stock at time of publishing. By John Alexander Dogs that have oral squamous cell carcinomas often need surgeries that disfigure their jaws and lower their quality of life – and in 20% of dogs diagnosed the cancer has metastasized to a point where surgery is no longer an option including Cornell researchers across five departments and institutes has found that an FDA-approved drug used in humans can be “remarkably effective,” researchers said which is the most common oral epithelial malignancy in dogs The drug substantially inhibited the growth of the tumors in mouse models and in dogs enrolled in a clinical trial One dog’s tumor nearly disappeared in a matter of weeks “It’s a super exciting clinical tool that we now have available,” said Santiago Peralta, associate professor of dentistry and oral surgery in the College of Veterinary Medicine (CVM) and senior author of the study “We are already getting calls and emails from colleagues and from dog owners from all over the world.” targets a downstream component of the RAS signaling pathway which regulates cell growth and which is implicated in a number of human and animal cancers Approved for the treatment of melanoma in humans trametinib has been found to be safe for use in dogs and relatively inexpensive – a month’s worth of treatment is around $100 to $200 depending on the size of the dog researchers created new cell lines from the tumors of dogs diagnosed in the clinic They tested a number of therapeutic agents on the cells and then moved to mouse models where trametinib was particularly effective “I’ve never seen results like that in mice before,” said first author and research associate William Katt “And I was blown away when we saw the results in the dogs – being on a project that made it to the clinic and seeing the tumor nearly vanish in a couple of weeks was delightfully surprising.” with only four dogs enrolled; it’s now at 20 The researchers included the preliminary data because it was so encouraging with one dog showing 80% tumor regression and another 40% regression “What we’re seeing is that some dogs or some tumors are susceptible to this treatment whereas others are not,” Peralta said we’re seeing several cases where the response is remarkable.” Peralta and others are currently following up to try to understand the divergent tumor responses – research that could shed light on the RAS pathway and have implications across cancers and species The original cell lines created for the experiment could also spur more research Katt plans to add the cell lines to open-access depositories for other researchers’ use there’s a huge toolbox to work with,” Katt said “The first thing I did for this study was to look for existing cell cultures out there for these canine cancers Peralta said he doesn’t expect trametinib to cure the oral cancers completely but that it could be used to shrink them before surgery and result in less destructive interventions and improved quality of life “There’s often this window of opportunity between diagnosis and surgery – treating the dog in this window makes sense because Katt emphasized that the research was a team effort leveraging Cornell’s strengths and breadth “This speaks very positively to what we can do almost entirely in-house,” he said “and to just how much leverage and scientific power we have with the collective wisdom and expertise and facilities on this campus.” Distinguished Professor of Arts and Science in Chemistry in the College of Arts and Sciences and CVM director of genomics in the Cornell Institute of Biotechnology; Jordan C Warshaw of Prism Veterinary Dentistry in New York City; and Kristiina Keikinheimo of the University of Turku The study was supported with funding from the Cornell Richard P the National Cancer Institute and the Maritza and Reino Salonen Foundation Get Cornell news delivered right to your inbox By Both the injectable and oral forms of semaglutide, a glucagon-like peptide-1 receptor agonist, have gained recent attention for their effectiveness against weight gain, high blood sugar, and potentially against alcohol cravings A new clinical trial, co-led by endocrinologist and diabetes expert John Buse, MD, PhD, and interventional cardiologist Matthew Cavender, MD, MPH at the UNC School of Medicine has shown that the oral form of semaglutide can significantly reduce cardiovascular events in people with type 2 diabetes and atherosclerotic cardiovascular disease “Heart attacks and strokes are among the most common and devastating complications of diabetes,” said Buse Caviness Distinguished Professor of Medicine and Director of the UNC Diabetes Care Center “Semaglutide has been a main stay of our efforts to reduce heart attack and stroke in people with diabetes Having an oral option to deliver this highly effective therapy is a big advance.” Results from the rather large, international trial were published in the New England Journal of Medicine and presented at the American College of Cardiology’s Annual Scientific Session & Expo in Chicago Type 2 diabetes is a progressive disease that affects one’s ability to control blood sugar levels People with the condition need to closely monitor their diet and activity and may need to take medications as their blood sugar becomes more difficult to manage Those with type 2 diabetes are at a significantly higher risk of cardiovascular disease because they may develop high blood pressure Glucagon-like peptide-1 (GLP-1) receptor agonists have shown much potential for lowering blood sugar but little is known about whether the oral form of semaglutide actually decreases major cardiovascular events The Semaglutide cardiOvascular oUtcomes triaL (SOUL) recruited 9,650 people for the study who have pre-existing cardiovascular disease The trial was sponsored and funded by pharmaceutical company Novo Nordisk Participants were divided into a placebo group (no medication) and a drug group to see if those taking oral semaglutide were more or less likely to experience major cardiac events Both groups were given standard-of-care glucose-lowering and cardiovascular risk-reducing therapies according to local guidelines Those in the medication group took a once-daily 14mg dose of oral semaglutide Researchers found that oral semaglutide decreased the risk of major cardiovascular events by 14% compared to placebo across age and gender Of all types of major cardiac events studied in the clinical trial nonfatal myocardial infarction saw the greatest reductions in risk The effect of oral semaglutide on cardiovascular outcomes was consistent with other clinical trials involving injectable semaglutide but more trials are needed to determine if one method may be more effective than the other at reducing major cardiovascular events Media contact: Kendall Daniels Rovinsky Have a question? Need to reach the UNC Health News Team Call: (984) 974-1140 UNC Health Social Media Terms of Use Site Map The aim of this report is to provide a comprehensive baseline assessment on the global oral health targets to track implementation progress of the Global oral health action plan 2023–2030 The report offers an overview of the current situation and serves as a reference for future reports progress can be tracked every 3 years until 2031 and reported back to Member States through the mandate outlined by the World Health Assembly resolution on oral health (WHA74.5) Metrics details Oral health is a crucial determinant of overall well-being face significant barriers to maintaining it Personalized oral health education and behavior modification using models like the Health Action Process Approach (HAPA) and Motivational Interviewing (MI) can address these barriers their individual limitations highlight the need for a combined approach Integrating these models with personalized education and oral care kits provides a holistic solution to address both motivational and practical barriers This study evaluates the effectiveness of such an intervention on oral health behaviors and outcomes in residents of informal settlement A quasi-experimental pre and post interventional study was conducted among 45 participants aged 18–60 years from three wards in Bhubaneswar The study was conducted between October 24 Participants were recruited through dental camps organised by our institute Baseline oral health behavior was assessed using a validated questionnaire based on four behavioral constructs: outcome expectancy (OE) and perceived barriers (PB) by faculty and postgraduate students of public health dentistry department Participants also received personalized oral health education and an oral care kit and behaviour towards oral health were recorded both at baseline (T0) and one-month post-intervention (T1) by same examiners Statistical analyses included paired t-tests and Cronbach’s alpha for internal consistency of the questionnaire significant improvements were observed in all behavioral constructs The mean outcome expectancy (OE) increased from 2.49 ± 0.20 to 4.15 ± 0.07 (p = 0.000) self-efficacy (SE) from 1.90 ± 0.14 to 3.81 ± 0.14 (p = 0.000) intention (I) from 1.92 ± 0.11 to 4.30 ± 0.33 (p = 0.001) and perceived barriers (PB) from 1.85 ± 0.11 to 4.04 ± 0.03 (p = 0.002) Clinical outcomes also showed significant improvements: the mean plaque index (PI) decreased from 1.9 ± 0.8 to 0.9 ± 0.4 (p = 0.000) and the mean oral hygiene index-simplified (OHI-S) decreased from 2.3 ± 1.4 to 1.5 ± 0.9 (p = 0.003) Internal consistency of the questionnaires was good across constructs with Cronbach’s alpha values ranging from 0.715 to 0.751 This study demonstrates that a holistic behavioural intervention combining personalized education behavior modification using HAPA and MI models and oral care kit distribution significantly improves oral hygiene behavior and clinical outcomes among residents of informal settlement The model addresses both motivational and access barriers providing a scalable framework for improving oral health in underserved populations Future research should explore the long-term sustainability of this approach and its applicability to other settings we hypothesized that combining HAPA with MI along with provision of basic oral care tool can improvise the oral health especially among the underprivileged populations who lack access to oral health awareness programmes and oral health care This study aims to assess the effectiveness of a combined intervention comprising personalized oral health education behavior modification through a custom-designed questionnaire based on HAPA and MI constructs and the distribution of a basic oral hygiene kit we intend to improve oral hygiene practices among underprivileged populations increase compliance with regular brushing and flossing and reduce plaque and oral hygiene index-simplified (OHI-S) scores we aimed to evaluate the association between behavioral constructs—such as outcome expectancy and perceived barriers with these clinical indices to understand the behavioral shifts that underpin improved oral health practices this study targets the marginalized urban population living in environments with limited access to resources and basic services such groups have been labeled as “slum dwellers” but this term is now widely recognized as pejorative and stigmatizing These communities are typically characterized by overcrowded and unplanned settlements intention and access to formal healthcare services we will use the term “residents of informal settlements” to refer to these communities living in precarious conditions This terminology is considered more respectful and appropriate for describing populations residing in such under-resourced urban areas Through this combinative approach this study may bridge the gap between intention and sustained behavior change in maintaining oral health in high-risk populations which previous studies have not addressed This quasi-experimental study assessed the impact of an intervention—comprising personalized oral health education and behavior modification through a questionnaire based on HAPA and MI constructs—on oral hygiene practices among residents of informal settlement in Bhubaneswar The study evaluated changes in oral hygiene behaviors and clinical oral health outcomes This study primarily involved quantitative data collection and analysis Pre- and post-intervention data on participants’ behavior and oral health outcomes were collected to determine the intervention’s effectiveness on oral hygiene practices We conducted oral health screening camps among the residents of informal settlements at three wards of Bhubaneswar These individuals belong to low-income groups with no or unstable employments such as daily wage labors Sanitation and ventilation in those settlements are poor They have limited access to health care including oral health care self-medication or alternative medicine rather than professional dental care Most importantly nutritional deficiency and lack of autonomy in health relation decisions are prevalent in these settlements following approval from the Institutional Ethics Committee (Approval No.: EC/NEW/INST/2022/3235) 45 participants were selected for the study Post hoc power analysis using G*Power (version 3.1.9.7) revealed a study power of 98% with an effect size of 0.5 all eligible individuals were provided with a detailed explanation of the study objectives Participants were informed that their participation was voluntary and that they could withdraw at any stage without any consequences Written informed consent was obtained from each participant before enrollment verbal consent was recorded in the presence of a witness all data collected were anonymized and coded with no personally identifiable information linked to the research findings Data were stored securely and were accessible only to the investigators (SP and PR) Participants eligible for inclusion in the study were adults aged 18–60 years diagnosed with gingivitis who were willing to meet all study requirements possessed the cognitive ability to understand and follow oral hygiene instructions including at least one index tooth to evaluate plaque and OHI-S Exclusion criteria included individuals who were current smokers or had quit smoking within the past year or those with systemic diseases that could impact study outcomes Participants were also excluded if they were on long-term antibiotic therapy Convenience or purposive sampling was followed by collaborating with local health clinics or NGOs to identify potential residents of informal settlements who gave their consent to participate each scored on a five-point Likert scale (1 = strongly disagree to 5 = strongly agree) Personalized as well as community based oral health education was provided Each selected participant completed a custom-designed questionnaire (Supplementary Table 1) and responses were recorded in the data extraction sheet The responses to the questionnaires were collected anonymously without linking responses to individual participants ensuring complete anonymity in data collection and analysis Education was delivered at both community and individual levels Community-level workshops included motivational talks on oral hygiene’s benefits and dietary influences on oral health The lectures were delivered by faculties and post graduate dental students of community dentistry department outside those settlements addressing small groups of 15 people in three sessions Audiovisual aids through power point presentation were used to demonstrate the brushing and flossing techniques one-on-one sessions were tailored to each participant’s specific needs One on one session was also taken by the faculties and post graduate dental students of community dentistry department Each participant received an oral hygiene kit participants were re-evaluated to assess changes in plaque index and behavioral constructs using the same custom-designed questionnaire from the baseline We have depicted the methodology schematically in Fig. 1. Schematic description of the methodology Data analysis was conducted using SPSS for Mac (version 28 A p-value ≤ 0.05 was considered statistically significant are presented as frequencies and percentages The baseline oral health behavior of residents of informal settlements was assessed by summarizing Likert scale responses for each item in the constructs Paired t-tests compared the means of behavioral constructs and OHI-S between pre- and post-intervention groups Cronbach’s alpha measured the internal consistency among questionnaire items while chi-square tests examined improvements in index grades and associations between behavioral constructs and oral health behavior at T0 and T1 each behavioral construct was assessed in three categories If the post-intervention score is more than pre-intervention score If both scores are equal or post intervention score is less than pre-intervention score The differences in post and pre-intervention score of PI and OHI-S were calculated To evaluate the influence of change in behavioral constructs on differences in plaque index and OHI-S we conducted multivariate regression analysis The internal consistency of the questionnaire items was assessed using Cronbach’s alpha with scores indicating good reliability across all constructs: outcome expectancy (α = 0.751) These values demonstrated a satisfactory level of internal consistency supporting the reliability of the measures used in the study The study comprised of 45 participants who gave consent to participate. The mean age among the study participants was 40.13 ± 11.91. The socio-demographic details are described in Table 1 Majority (n = 17) of the subjects belonged to the age group of 31–45 years of age followed by participants aged 46–60 years Males comprised of 51.1% of the study population The habit of tobacco consumption was seen among 66.7% of participants Baseline responses across the behavioral constructs revealed low outcome expectancy and self-efficacy in practicing good oral hygiene Only 4.4–13.3% of participants strongly agreed with statements about the positive effects of brushing while 2.2–6.7% agreed with these statements 0–11.1% strongly agreed on following proper brushing and flossing techniques most participants displayed low intentions for regular oral hygiene practices with 42.2% disagreeing that improved oral hygiene could benefit systemic health The intervention resulted in significant improvements across all items in the four behavioral constructs. Mean scores increased post-intervention for outcome expectancy, self-efficacy, intention, and perceived barriers, with statistical significance (p = 0.000) observed for all items. Pre- and post-intervention mean scores are detailed in Table 2 Post-intervention improvement of behavioral constructs While the plaque index and OHI-S scores showed overall improvement and poor) was not statistically significant (Chi square P value = 0.328 for PI and 0.642 for OHI-S) across all groups The mean difference in PI and OHI-s were found to be 0.13 ± 0.94 and 0.36 ± 1.45 respectively These values suggested a slight improvement in both the indices High standard deviations suggested a large variability Overall model significance in this test did not show any significant effect (Pillai’s Trace value = 0.201 p = 0.83) of behavioral constructs on either PI or OHI-S t Individual predictor significance in this test showed that SE1 has a potential effect on OHI-S PB3 (F value = 2.86) and I4 (F value = 2.49) have moderate effect size though none were statistically significant Rest of the behavioral constructs did not affect any of the indices R² values showed that behavioral constructs explain some variance (28.4% for PI This study evaluated the effectiveness of a comprehensive intervention combining personalized oral hygiene education behavior modification using HAPA and MI constructs and provision of a basic oral care kit among residents of informal settlements of Bhubaneswar Our results indicate significant improvements in oral hygiene behavior which was reflected in improvement of plaque index and OHI-S supporting the hypothesis that a multifaceted approach can effectively enhance oral health practices among the under-privileged population in low-resource settings the study indicated that merging behavior modification strategies with direct oral health education and access to basic oral care tools yields a sustainable impact and intention to maintain regular dental visits showed positive shifts across the analyzed constructs These findings support the idea that addressing motivational and practical barriers holistically can enhance long-term oral hygiene adherence They attributed this to the low socioeconomic status of their participants which may have hindered behavior change during the interventions we included the distribution of basic oral hygiene kits to facilitate observable improvements in clinical outcomes These visible changes could then motivate residents of informal settlement to adopt and sustain positive oral health behaviors The observed Cronbach’s alpha range for OE 0.740 and 0.747 respectively which indicated that the reliability of the measurement instruments used in this study is good and there is an appreciable level of internal consistency across all constructs and insufficient knowledge on oral hygiene highlights the need for targeted interventions among underprivileged populations These individuals are often at higher risk for oral health issues and less likely to adopt preventive practices The approach used in this study could be adapted for similar at-risk groups focusing on both individual and community-level teaching and kit distribution to maximize outreach and impact the attrition rate in the present study is only 6.25% which further supports the generalizability of this intervention The significant improvement in all items of SE construct indicated a boost in the participants’ confidence to perform oral hygiene practices which may lead to sustained behavior change the significant improvement in OE construct explained the strong belief in benefits of appropriate oral hygiene practices which would motivate them to maintain the practice further Observing the improvement in oral health behavior in the construct reflected the effectiveness of this mixed intervention in overcoming barriers to oral hygiene practices highlighted the impact of this intervention on motivation and plans for adapting good oral hygiene practices The present study’s strength resides in its amalgamation of three interventions each independently validated for their efficacy in fostering and sustaining oral health behavior follow-up data were collected only after one month potentially limiting the demonstration of significant improvements in clinical outcomes and behavioral changes the sole follow-up session post-intervention allowed for limited interaction time between participants and dentists we may suggest that future research should incorporate longitudinal assessments at 3 and 12 months to evaluate behavior retention and relapse rates such as periodic follow-up sessions or digital reminders could be explored to sustain oral health behavior the absence of a control group precludes comparative assessments of outcomes we implemented a quasi-experimental pre-post study design where each participant served as their own control Baseline (T0) and post-intervention (T1) assessments allowed us to evaluate changes in behavioral constructs and clinical indices The statistical significance of these changes strongly suggests the effectiveness of the intervention Future research incorporating a randomized controlled design with a control group would further validate the intervention’s effectiveness Although the post hoc power analysis indicated a study power of 98% with an effect size of 0.5 and a significance level of 0.05 the sample size of 45 participants may limit the generalizability of our findings Future research should aim to recruit a larger and diverse samples to enhance the external validity of the study Association of these behavioral constructs with improvements in additional clinical parameters such as bleeding on probing and gingival inflammation can be looked for in future studies which may require long follow up periods There are several confounding factors which may have influenced the present result and lack of access to healthcare are some of the possible factors low educational level among the participants may have influenced their initial understanding of oral hygiene practices affecting the degree of change observed even after the intervention cultural norms and traditional beliefs including use of home remedies or reliance on quacks for oral health care may have affected compliance with the recommended hygiene practices Financial constraints and competing priorities like daily livelihood concerns could also limit participants’ ability to sustain improved oral hygiene behaviors beyond the intervention period Future studies should incorporate qualitative assessments to better understand the role of these external factors in behavior modification and intervention effectiveness this study demonstrates that a holistic approach effectively improves oral hygiene behaviors and clinical health outcomes among underserved populations Future studies could explore the long-term sustainability of this model ideally employing larger sample sizes to further validate its applicability and scalability which has the potential to mitigate oral health inequalities and enhance overall well-being in underprivileged populations aligning with broader public health agendas Available - requests for materials should be addressed to swagatikapanda@soa.ac.in Oral Health Equals Total Health: A Brief Review Dasson Bajaj P, Shenoy R, Davda LS, Mala K, Bajaj G, Rao A, et al. A scoping review exploring oral health inequalities in India: a call for action to reform policy, practice and research. Int J Equity Health. 2023;22:242. https://doi.org/10.1186/s12939-023-02056-5 A review of approaches for dental practice teams for promoting oral health Improving periodontal outcomes: merging clinical and behavioral science Health behavior models and oral health: a review Modeling Health Behavior Change: How to Predict and Modify the Adoption and Maintenance of Health Behaviors Health action process approach in oral health behaviour: Target interventions Effectiveness of Motivational Interviewing on adult behaviour change in health and social care settings: A systematic review of reviews A meta-analysis of the health action process approach Health Psychol J Div Health Psychol Am Psychol Assoc Health Action Process Approach (HAPA) as a Theoretical Framework to Understand Behavior Change A key challenge for motivational interviewing: training in clinical practice Barriers to implementing motivational interviewing in addiction treatment: A nominal group technique process evaluation Behavioral Interventions on Periodontitis Patients to Improve Oral Hygiene: A Systematic Review Self-regulation in oral hygiene behaviours in adults with gingivitis: The mediating role of coping planning and action control Effectiveness of brief motivational interviewing on perceived importance interest and self-efficacy of oral health behaviors: A randomized clinical trial Impact of Oral Health Education on Oral Health Knowledge of Private School Children in Riyadh City Effectiveness of motivational interviewing at improving oral health: a systematic review Motivational interviewing in improving oral health: a systematic review of randomized controlled trials Oral Health Coaches at Well-Baby Clinics to Promote Oral Health in Preschool Children From the First Erupted Tooth: Protocol for a Multisite Correlation between oral hygiene and periodontal condtion Brief Motivational Interviewing in Dental Practice The Effect of a Personalized Oral Health Education Program on Periodontal Health in an At-Risk Population: A Randomized Controlled Trial Active-involvement principle in dental health education The Impact of Motivational Interviewing in Reducing Plaque and Bleeding Indices on Probing in Adult Users of the Family Health Strategy Effect of a health-education program using motivational interviewing on oral health behavior and self-efficacy in pregnant women: a randomized controlled trial Variables associated with oral health-related self-efficacy – results of a cross-sectional study Dental self-efficacy as a determinant to oral health behaviour oral hygiene and HbA1c level among diabetic patients The Relationship of Oral Health Literacy and Self-Efficacy With Oral Health Status and Dental Neglect Download references This research is funded by STS Program of Indian Council of Medical Research Open access funding provided by Siksha 'O' Anusandhan (Deemed To Be University) Siksha ‘O’ Anusandhan deemed to be University Department of Oral Pathology and Microbiology and manuscript writing; SP – research concept data curation and manuscript writing; RD – Data collection and manuscript editing; KR – Data collection and manuscript editing The authors declare no conflicts of interest Download citation DOI: https://doi.org/10.1038/s41405-025-00329-5 Towards Universal Health Coverage for Oral Health by 2030 WHO convened the first-ever Global oral health meeting in Bangkok as part of the preparatory process for the 4th United Nations High-level Meeting (HLM4) on NCDs in 2025. This landmark event aimed to accelerate and scale up the prevention and control of noncommunicable diseases (NCDs) with a particular emphasis on oral diseases to achieve universal health coverage (UHC) for all A significant outcome of this meeting was the adoption of the Bangkok Declaration: "No Health Without Oral Health" Global strategy and action plan on oral health 2023–2030