VANCOUVER, British Columbia, May 05, 2025 (GLOBE NEWSWIRE) -- Today, Zenterra Developments (Zenterra) is officially announcing Atlin at Clayton Crest
the first of seven condo buildings that will make up the Clayton Crest master-planned community in Surrey’s West Clayton neighbourhood
West Clayton is set for major growth with projects like the Surrey-Langley SkyTrain extension
Atlin at Clayton Crest is the first development in this booming area
offering buyers a prime opportunity to invest in a fast-growing neighbourhood
“Not only does Atlin mark the first step for the Clayton Crest community
but it adds excitement to the exceptional growth and opportunities we are seeing in the West Clayton area
and these homes offer an excellent opportunity for residents to get in early on what promises to be a thriving area,” said Derek Fenton
Clayton Crest offers an affordable and accessible housing option in the Lower Mainland
but Clayton Crest provides a solution—modern
comfortable homes at a highly competitive price
Located in the growing community of West Clayton
the area holds strong potential for market appreciation
Buying early means lower barriers to entry and a chance to see a positive return on investment as the community develops
Located within walking distance to the future Skytrain Station at 184th Street and Fraser Highway
residents will be connected to the metropolitan cores of the Lower Mainland
They can easily commute to urban hubs within an hour or less
allowing them the flexibility to work and play in more densified regions
The Fraser Valley offers a sense of tranquility
and now that the SkyTrain extension is underway
purchasers can have the best of both worlds: city access and valley serenity
Residents can easily live car-free in the Clayton Crest community
but underground parking is available for those who drive
The location offers convenient access to Highway 1 and the U.S
ample bike storage ensures flexible transportation options for everyone
“This community represents a perfect blend of nature and city living
with easy access to urban centres and amenities
while also enjoying the tranquility of the Fraser Valley
unobstructed views of the Fraser Valley and North Shore mountains
bringing a peaceful and picturesque vibe to their homes,” said Fenton
Clayton Crest offers sweeping valley and mountain views
with rooftop patios designed to make the most of the scenery
creating a relaxed setting for residents to unwind or connect
The development includes a range of amenities aimed at enhancing everyday life
and a co-working space with an adjoining patio for those looking to take their work outside
Clayton Crest provides an integrated approach to modern living
the first building in a new master-planned community
and 3-bedroom condos designed to suit various lifestyles
Buyers can choose between two designer colour schemes to personalize their space
Standard features include solid shelving in closets
The homes are designed to balance affordability with practical details
creating functional and comfortable living spaces
Zenterra has also included an on-site daycare facility in Atlin
filling a gap in the much-needed stock of daycare facilities in Surrey
Surrey falls below the Canadian average of 27.2 spaces per 100 children
with a 2023 analysis showing there are 17.9 licensed child care spaces per 100 children aged 0–12
Purchasers will enjoy the convenience of an on-site daycare with priority access for residents
reducing the stress of long childcare waitlists
“We understand that families and new homebuyers in Surrey
especially those looking to start a family
are facing challenges in finding daycare options
Atlin will ease that burden by giving residents early access to the facility
with the opportunity to enroll their kids in the new school developments nearby,” said Fenton
Developed by award-winning Zenterra Developments
Atlin at Clayton Crest is a community built for lasting value
named 2025 Multi-Family Home Builder of the Year by the Canadian Home Builders Association BC
has earned over 100 national and provincial award nominations
and sustainable design ensures Atlin at Clayton Crest will be a thriving investment
With a reputation for creating thoughtfully designed communities
Zenterra sets the standard for residential excellence in the Fraser Valley
Media Contact: Amanda BreenTalk Shop Mediaamanda.breen@talkshopmedia.com
Zenterra Developments (Zenterra) is a fully integrated real estate development company overseeing every aspect of each project from start to finish
With more than 100 award nominations and 35 current wins
Zenterra is one of the largest multi-family home builders south of the Fraser River
Zenterra is locally-owned and operated and known for creating award-winning
uniquely designed and attainable multi-family homes in vibrant neighbourhoods across the Fraser Valley
The city of Wichita Falls said Friday afternoon the National Weather Service forecasts the Wichita River will crest at about 1 a.m
Saturday and also forecasts a break in the rain over the weekend
But the city warned two road closures were in place and continued road closures are still possible
The release said the Emergency Operations Center will transition to standby
The Wichita Falls Fire Department will continue to drive through flood prone neighborhoodsto monitor road conditions
The release said if the situation changes and evacuations are needed
all local agencies are staged and ready to activate the emergency plans already in place
More: City anticipates possible street closures because of flooding
More: MSU Texas students compete at Model UN
The Razor Crest 75331 consists of 6,187 pieces
which makes it the third largest Star Wars set in brick count
The resulting build is impressively large at 20" long
This is an offical Ultimate Collector Series - or UCS - set
The UCS models are the largest and most detailed Star Wars sets that LEGO produces and an obvious pick for collectors
They are also technically challenging build that are aimed at adult (18+) builders and the instruction manuals are often hundreds of pages long; the Razor Crest is no exception with about 250 pages
This is a faithful recreation of the iconic ship from The Mandalorian TV series
The detailed interior is easily accessible and features two removable engines and cockpit
a cargo compartment with space for the included Blurrg minifigure
a LEGO minifigure sized carbon-freezing chamber
and detachable escape pod with space for another minifig
Five minifigs are included: the Mandalorian (set exclusive)
the interior is made of different color-coded interior components and different steps are individually packaged in bags to make the process more user friendly
Although the Razor Crest is fully intended to be more of a display piece
it's more interactive than most other UCS sets with a lot of internal elements that you can explore even after the build is completed
Eric Song is the IGN commerce manager in charge of finding the best gaming and tech deals every day. When Eric isn't hunting for deals for other people at work, he's hunting for deals for himself during his free time.
Absolutely ridiculous that anyone would pay that much for a model set
They're gonna need to drop the price a lot more than that..
Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInWICHITA FALLS
Texas (KAUZ) - Although rainfall in the area appears to be over - for a few days at least - the Wichita River has not yet crested as recent rain continues to flow into the waterway via creeks and drainage systems
The river is expected to reach its highest around 1 a.m
Saturday before slowly diminishing back to regular levels
Two Wichita Falls streets are closed downtown due to flooding
Tulsa Street and Woods Street are both closed from Smith Street to Homes Avenue
City officials will continue to monitor the situation
but the Emergency Operations Center will transition to standby while continuing to monitor conditions around town
This newscast is updated weekdays at 6am
Army Corps of Engineers is preparing for the Mississippi River to reach some of its highest water levels in recent years in New Orleans and Baton Rouge
the river is expected to crest at 40.5 feet in Baton Rouge around Friday and 16.5 feet in New Orleans on Saturday
the Corps did a test opening of the Bonnet Carre Spillway near LaPlace on Monday
Residents across South Louisiana are being urged to follow updates from the Corps and local emergency management offices as water levels evolve over the coming days
Host Karen Henderson spoke with Louisiana State Climatologist Jay Grymes to learn more about the Corps’ flood fight protocols
This interview was edited for length and clarity.
the Corps tested the Bonnet Carre Spillway in LaPlace on Monday to make sure it's ready if it needs to be open to help avoid any flooding
Where's all this water coming from and what areas of the state are most at risk
JAY GRYMES: The river has been rising for a while now
lots of your listeners may remember the significant flooding that they had up in Kentucky
that water takes as much as two weeks or so to get down here
and that's been generating this rise along the Mississippi
we've got flood warnings on the Mississippi through most of the reach of the Mississippi
and that extends from north of Baton Rouge through Baton Rouge and down towards New Orleans
Now it's important to remember when we talk about flooding on the Mississippi and we talk about flood stages on the Mississippi
we're generally not incorporating the levees
Baton Rouge is expected to go to “major flood.” Yet that'll still be well below the tops of levees for Baton Rouge
So the reality of the situation here is that for the vast majority of us high water on the Mississippi not only is something we can expect every spring
but it's just not likely to be that big of a deal
the US Corps of Engineers is looking at testing the Bonnet Carre Spillway
These are tools to relieve pressure on our levees and how likely are these to be used because they're needed
What we're talking about is when the water gets exceptionally high
it also starts to move at a fairly quick pace down the Mississippi River
not so much the height of the water that the Corps is trying to control
without getting too caught up in the numbers
or at least a partial opening of Bonnet Carre
and that seems like it's at least a decent chance of happening
The Corps is already in flood fight phase 1
and what that typically means is two inspections per week up and down the entire stretch of the levee just checking for things like seepage
and other little incidental problems along the levee
Now over the next day or the next couple of days
they're probably going to go to flood fight stage 2
and that's when the river in New Orleans gets to 15 feet and steadily rises
The thinking is that the river is certainly going to get above 15 feet
staying on top of the potential for some minor problems along the levee
are there any flood warnings that have been issued due to the water that we know is coming or that has been coming
GRYMES: We do have flood warnings at Red River Landing
there are sites that are under flood warnings that are in flood technically
the key here is to remember that terminology can be a little bit misleading because even though the river is technically in “flood,” it is still readily contained by the levee system
So it's not as if communities along the Mississippi have to worry about real flooding
When we talk about flooding on the Mississippi
When's the last time the Bonnet Carre has been opened and can you talk to us about the environmental impact from the spillway
GRYMES: So the last time the Corps had to use the Bonnet Carre was back in the spring of 2020
It’s also worth remembering that between about 2016 and 2020
So the river goes through ebbs and flows in terms of its spring crests
we're shunting a lot of fresh water and also sediment and maybe a little bit of agricultural runoff out of the Mississippi into Lake Pontchartrain
and that's where we can start to see environmental impacts to the lake system because that surge of freshwater changes the salinity of the lake
It has an impact on oyster and shrimp fishermen
now the good news this year is I think that the opening of Bonnet Carre will be brief enough and limited enough that the environmental footprint will be fairly minor
what do you expect to see as we move through this week and when do you believe that the flood threat will be over
GRYMES: So it looks like the crest of the high water will be the last few days of April
That's where we're expecting the crest to pass Baton Rouge
and then it typically takes about one day for that crest to move from Baton Rouge down to New Orleans
that doesn't mean that the water is gonna drop off rapidly
but this crest is going to be a relatively short event
keep in mind the Mississippi typically is high in the spring anyway
not all that unusual that we're looking at high water on the Mississippi
The unusual aspect of it is that it's going to be high enough that the Corps has to consider using the Bonnet Carre as a diversion to take a little bit of that pressure off of the levees as that water moves past the Crescent City
EAGLE, Idaho, May 01, 2025 (GLOBE NEWSWIRE) -- Pacific Crest Services (“PCS”)
a leading platform for independent insurance agents
announced today that it has secured a minority growth investment from Long Ridge Equity Partners ("Long Ridge")
a growth-focused private equity firm with deep experience in the financial technology and services sectors
PCS will continue to operate under the leadership of its existing management team
PCS has established itself as a premier partner for entrepreneurial agents through its unwavering focus on mission
The company serves more than 250 independent agencies across 36 states and maintains relationships with over 250 carriers
The growth capital will fuel continued investment in key areas of the business
and capital solutions – all aimed at equipping independent agents with a full suite of tools and resources
"We’re excited to partner with Long Ridge as we enter this next chapter of growth," said Shawn Webb
"Their experience scaling high-growth financial services businesses will be invaluable as we continue building a comprehensive platform for entrepreneurial agents to launch
Shawn Webb and Jason Webb founded PCS in 2008 with a mission to empower independent agents to build and grow successful businesses
PCS provides a unique platform that offers agents access to top carriers
and compliance resources – enabling agents to better serve their customers and achieve their ambitions
“PCS offers a strong value proposition to its agents and partners
combining a robust platform with a broad network of carrier relationships,” said Jason Melton
and the PCS team have built a trusted brand within the agent community
and we are excited to support them as they continue to scale and deliver exceptional service to their agents and carrier partners.”
Evolve Capital served as exclusive financial advisor and Wiggin and Dana LLP served as legal counsel to PCS
& Stewart LLP served as legal counsel to Long Ridge
a wholesaler based in Prince George’s County
has initiated a voluntary recall of three of its products after an employee spotted “a small glass fragment” on top of a piece of bread
The recall is for the brand’s Ancient Grains Hoagie Rolls
Multigrain Sourdough and its Whole Grain Multigrain Bread
The company said Wednesday that all the products still on store shelves have been accounted for
The affected products were distributed to Pennsylvania, California, Maryland, Connecticut, Delaware and Ohio, according to the FDA
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The FDA listed the recalled bread as Class II
which means the items may cause “temporary or medically reversible adverse health consequences.”
An investigation from the company found the glass contamination came from sunflower seeds supplied by JJ Nuts
Crest Hill Bakery said it has stopped working with the company that manufactured those seeds
Crest Hill Bakery said it believes the company has “effectively resolved the issue.”
Crest Hill Bakery operates out of a 150,000-square-foot space in Glenn Dale, and sells wholesale products
Cody Boteler
cody.boteler@thebaltimorebanner.com
Cody Boteler is a reporter on The Banner’s Express Desk
trending stories and interesting things in and around Baltimore
His work has appeared in The Baltimore Sun
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Crest Hill (Photo provided by Joliet Police Department)
Joliet police arrested a man Tuesday for allegedly shooting video of a former girlfriend without her knowledge
Jose Rendon, 22, of Crest Hill was arrested on four counts of unauthorized video recording and live video transmission
Rendon is “a past boyfriend” of a woman who notified police July 25 that she found “a video recording device hidden in her bedroom,” according to a news release from the Joliet Police Department.
“It was determined that Rendon owned the device and had allegedly recorded the victim without her consent,” according to the release
who confirmed that he recorded the victim without her consent,” according to the release
Detectives obtained an arrest warrant for Rendon on Monday. He was arrested Tuesday after turning himself in, police said. Rendon was taken to the Will County Adult Detention Facility.
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A PCT hiker spent an hour "death-gripping" an unstable cliff in southern California before rescue personnel managed to pluck her off
A search and rescue team saved a Pacific Crest Trail hiker who was stuck on a cliffside in southern California during an “intense” operation caught on video on Sunday
according to the Riverside County Sheriff’s Office
In an Instagram post
the department said that the unnamed hiker became trapped on a cliffside near Whitewater
and managed to alert emergency services through her Garmin device
By the time a helicopter managed to lower a rescuer to her
she had been perched on the side of the face for an hour
which she was exhausted from that position for over an hour
the rescue specialist determined the safest option was to bear hug her and climb to the top,” the department wrote
“He just could not risk asking her to lift her arms that she was clearly death-gripping the cliff with in order to place a rescue strap on.”
A post shared by Riverside Sheriff Aviation (@rso.aviation)
as the rescuer coordinates with the helicopter crew over radio
the hiker shouts that she is falling; the rescuer urges her to grab onto his back
then tells the helicopter to carry them away from the wall
When the responding crew member asks whether he wants the helicopter to carry them left or right
you’re dragging us right into the wall,” he says
the helicopter crew slowly works the pair up the cliff until they’re finally resting securely on top of it
The Riverside County Sheriff’s aviation unit has chronicled its rescues of a handful of hikers on Instagram over the past few months, including a 23-year-old PCT hiker in “serious medical distress” who was airlifted out alongside his two companions
The 30-mile thru-hike was the ideal trip for putting our backpacking and hiking candidates through the wringer
please have patience while we stay live during this process
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Root Beer floats can come out of anywhere when your hiking the Pacific Crest Trail
this one magically appeared on her birthday in the desert of Southern California
2025 — TD Grad Celia Peterson and friend Jensen Douillard have made it to mile 179 on their 2,650 mile hike to Canada
“I feel like I needed this to be pushing myself,” Peterson said on Thursday
an unincorporated town of 3,000 with a retriever for a mayor near the San Jacinto Wilderness
but it is cool how everything is so different everyday.”
Jensen Douillard cleans out a shoe at Warner Springs Community Center northeast of San Diego
He and Celia Peterson received a food package for resupply to get them to Idyllwild some 70 miles north
That ranges from the people they meet to the landscapes that change with each stretch of the trail
The pair reached Warner Springs Community Center last Thursday
April 17 and were able to get a shower and washed their clothes using shampoo and buckets before heading on to Idyllwild
Community Resource Center in Warner Springs provided a chainlink fence to air dry some bucket laundry
The next day they ran into a funny little sign
BBQ and a toilet and even a small swimming pool
As water sources had gone a bit sour in the area - one cistern reportedly flavored by a dead rat - the couple took the leap and sought out Mr
actually and it happened to be his birthday
the same as Celia and he was having a huge trail magic party for all who came
Jensen and Celia dined on free bbq hamburgers
refilled their water and were able to get out of the intense sun in the shade screens of Mr
Mike DeBenedetti pours a float for Celia Peterson at the impromptu birthday bash
That trail magic seems to flow once hikers let go
Peterson said there was huge satisfaction in finishing a days hike
getting camp set and enjoying dinner to the incredible sunsets that perform at their tent door
A light meal at the Paradise Valley Cafe on Easter provided the couple a boost and thousands of necessary calories
noting they were finishing some grueling elevation gains and both she and Jensen are battling some blisters
Jensen’s pinky toe was so inflamed it grew to twice its size
“ET phone home Pinkie Blister” was the caption on his Instagram
She said an elevation gain of several thousand feet combined with some poor trail conditions to really test her
She said a section of the trail had multiple downed trees in steep slopes and she had to remove her backpack to crawl under at some points
“The last four miles took so long,” she said
noting she cried at points because of the difficulty and soreness in her swollen ankle
You could see all of Palm Springs and the mountains - it was worth it.”
One pair down - shoes don’t last long on the PCT - 400 miles a pair if you’re taking care of your feet
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Players enjoy a pickleball game in a file image
Wildwood Crest officials say they want to keep the play happy
and have approved new rules for pickleball and basketball that they describe as ‘play nice’ rules
WILDWOOD CREST — The borough has a simple message for pickleball fans: Play nice
The Borough Commission on Wednesday approved an ordinance outlining rules for the community’s basketball and pickleball courts
or as Mayor Don Cabrera described it at the meeting
“the ‘play nice at the pickleball courts’ ordinance.”
including shouting matches and other issues
but he said he has not heard of anything that escalated to the point of a fight
There have been times when police have been called to the courts
but the issues were resolved in a conversation
But the borough wanted to have an ordinance on the books in case things escalate any further in the future
so that police would be able to issue summonses and to make the rules clear if anything someday ends up in court
“There hasn’t been anything physical yet,” he said
adding the borough wants to head off any problems before things reach that point
with a growing demand for court space in multiple shore towns
that has meant players trying to commandeer nearby tennis courts
The ordinance also specifically prevents players from designating skill levels or competitive games
stating that courts are public and open to all skill levels
The Ocean City Spring Block Party will return to downtown Asbury Avenue from 9 a.m
“People just have to place nice and let everyone use the courts,” Cabrera said
“We want everyone to respect the sport and for everyone to get along.”
As approved after a public hearing Wednesday
the new ordinance outlines rules for play and behavior at both the basketball courts at Scoop Taylor Park
and the pickleball and tennis courts at 6300 Ocean Ave
There are eight pickleball courts there and four tennis courts
two of which can be modified to allow more pickleball room
The new ordinance mandates that pickleball may only be played at the designated courts
and in turn that the courts can only be used for pickleball
physical force or other behavior that could disrupt the games and a prohibition against players hanging their own signs
“Courts are for ‘social play,’ and everyone is welcome – No designating of ‘competitive play,’” reads rule No
The basketball rules follow a similar pattern
including the same prohibition against glass on the courts
and keeping scooters and other devices off the courts
Cabrera said the borough does not have any plans to station someone at either court to make sure the rules are followed
Violators get one warning from Crest staff
A second violation means a borough official can kick the person off the court
Ocean City’s pickleball community successfully lobbied to reduce a fee hike planned for this year
“Failure to leave immediately constitutes defiant trespass subjecting the person to prosecution to the fullest extent of the law in addition to any other penalty provided for in this ordinance,” it reads in both sections
The ordinance amendment makes no mention of fines
The borough code covering all parks and public areas
sets a maximum penalty of a $2,000 fine or up to 90 days in jail
That code includes prohibitions against fireworks
bbarlow@pressofac.com
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Match Recap: Women's Tennis | 4/21/2025 10:46:00 PM
(4/21/25) – The Kean University women's tennis team defeated Cedar Crest College
The Cougars were victorious in all but one singles matchup as Eve Hunter and Delali Doe won in straight sets at third and sixth singles
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Print A stranded hiker was rescued by helicopter on Sunday after she spent more than an hour clinging to the side of a steep cliff along the Pacific Crest Trail
The terrifying image of the woman clutching the side of the cliff with a drop that spanned hundreds of feet was captured in bodycam video posted by the Riverside County Sheriff’s Office Aviation Unit
Rescuers responded to a 911 text message at 10:11 a.m
from the Whitewater Preserve area just south of San Bernardino County
The woman sent an emergency text using her Garmin-style communications device
Two helicopter pilots and three crew members found the exhausted hiker stranded off the side of a cliff, about 20 to 30 feet from the plateau. Officials described the incident as “an intense, technical rescue” in an Instagram post.
The hiker’s shoes barely gripped the rocks and she was still carrying a heavy backpack full of supplies, officials said.
California
These five places in California’s wilderness are jaw-droppingly beautiful but stealthily treacherous, taking the lives of explorers and rescuers alike.
A rescuer descended from the helicopter — communicating directions with the pilot as he moved along the cliffside — and bear-hugged the woman. At one point, the hiker screamed and grabbed onto the rescuer’s ears instead of his body to hold on, video shows.
“He just could not risk asking her to lift her arms, that she was clearly death gripping the cliff with, in order to place a rescue strap on,” the aviation team wrote on Instagram.
After a perilous few minutes, the helicopter lifted the rescuer and the hiker to the top of the plateau. The hiker, who was not identified, released her gear and quickly grabbed a water bottle.
The hiker did not suffer any significant injuries, officials said. She appeared to have a few bloody scrapes to her legs and knees in the video.
World & Nation
The hiker and a companion had wandered off the remote 53-mile hiking path that follows the northern California coastline of redwoods and black sand beaches when one of them fell 100 feet
“They both had quite the adrenaline dump once on top,” the aviation team wrote
It’s been a busy season for the rescue unit
The unit saved a man and a woman on March 3 along a ridgeline trail about 9,000 feet above Idyllwild. Three hikers were also rescued April 5 along the Pacific Crest Trail, with one suffering from serious medical distress.
Andrew J. Campa is a member of the Fast Break team at the Los Angeles Times, having previously covered the Eastside and San Gabriel Valley. Before, he worked at several medium and small daily newspapers and has covered education, sports and general news. He’s a proud University of Alabama (#RollTide), Cal State Fullerton and Pasadena City College alumnus.
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2025 at 1:14 pm CT.css-79elbk{position:relative;}The Crusade Burger II in Crest Hill along Renwick Road never captured the same success as the original location for Crusade Burger Bar in Yorkville along the Fox River
IL —A short-lived restaurant in the Joliet area
the Crusade Burger Bar West Renwick Road in Crest Hill
is now the subject of a six-figure civil lawsuit filed at the Will County Courthouse
A limited liability company called SD Basecorp II filed its lawsuit against Jessica Gomez and Rafael Gomez and The Crusade Burger
The lawsuit noted that Jessica and Rafael Gomez reside in Kendall County and on Aug
Crusade Burger signed a written lease that covered a time frame of more than five years
In December 2022, Joliet Patch broke the news revealing that Crusade Burger Bar II had opened in Crest Hill
bringing a unique dining experience to Will County
"We are very excited to have Crusade Burger Bar in the city of Crest Hill," Mayor Ray Soliman told Joliet Patch at the time
and they have a great reputation and following
They will become a destination point for our city along with our other fine restaurants
Crusade Burger II restaurant in Crest Hill only lasted about a year before it closed. This year, Patch reported that in addition to Crusade Burger II going out of business in 2023, the replacement tenant called the Jitterhead Breakfast Brunch and Coffee went out of business in late January after being open less than a year
the defendants were in default of their payment obligations under the lease in the amount of $113,813
the plaintiffs and defendants entered into a written agreement "whereby the defendants confirmed the delinquent amount of $113,813 and agreed to pay the aforementioned delinquent amount pursuant to an installment payment schedule," the lawsuit reads
the memorandum of agreement and the personal guarantee when they failed to pay the outstanding amounts due to plaintiff despite numerous demands to do so."
the defendants vacated the property prior to the expiration of the lease term
"Plaintiff has been damaged in the minimum amount of $184,803
Wheaton attorney Jason Cook of Sethna & Cook has asked Will County's judges to enter a monetary judgment against The Crusade Burger
Jessica Gomez and Rafael Gomez for the more than $184,800 in unpaid rent and "an award of plaintiff's court costs and attorney's fees."
Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts.
Results from CREST will be presented at an upcoming medical conference
The phase 3 CREST trial (NCT04165317) evaluating sasanlimab
an investigational anti-PD-1 monoclonal antibody
in combination with BCG as induction therapy with or without maintenance in patients with BCG-naïve
high-risk non-muscle invasive bladder cancer (NMIBC)
has met its primary end point of event-free survival (EFS) by investigator assessment
Treatment with sasanlimab/BCG was associated with clinically meaningful and statistically significant improvement in EFS vs BCG alone
commented on the trial in the news release
“Patients with BCG-naïve high-risk non-muscle invasive bladder cancer have high rates of recurrence and progression
These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naïve
high-risk non-muscle invasive bladder cancer
including patients with carcinoma in-situ (CIS)
providing prolonged event-free survival which may delay or reduce the need for more aggressive treatment options
could also help lower the treatment burden on both patients and health care systems.”
Shore is medical director of Carolina Urologic Research Center in Myrtle Beach
Pfizer reported that the overall safety profile of sasanlimab/BCG “was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab.”
sasanlimab is “a humanized immunoglobulin G4 mAb that binds to human programmed death-1 (PD-1) to block its interaction with PD-1 and PD-L1/PD-L2.” Pfizer added that the investigational treatment has demonstrated clinical efficacy in advanced solid tumors and advanced urothelial cancer in early-stage clinical studies
3 parallel-arm study comparing treatment with sasanlimab in combination with BCG (BCG induction with or without BCG maintenance) vs BCG (induction and maintenance) in patients with BCG-naïve
Study participants were randomly assigned to receive sasanlimab 300 mg by subcutaneous injection every 4-week cycle up to cycle 25 in combination with BCG once weekly for 6 consecutive weeks (induction period) followed (arm A) or not followed (arm B) by maintenance with BCG
or BCG induction and maintenance up to cycle 25 (arm C)
The primary end point was investigator-assessed EFS between arms A and C
EFS was defined as “the time from randomization to the earliest of recurrence of high-grade disease
or death.” Secondary end points included but were not limited to investigator-assessed EFS between arms B and C
overall survival (arm A vs arm C and arm B vs arm C)
complete response rate in participants with CIS at randomization
and health-related quality of life as measured by European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients.2
non-muscle invasive bladder cancer with BCG has not advanced in decades
Today’s pivotal Phase 3 CREST results are potentially practice-changing
representing the first advance in therapy for BCG-naïve
non-muscle invasive cancer in over 30 years,” said Roger Dansey
“These results reinforce Pfizer’s leadership in genitourinary cancer research and development
demonstrating our ongoing commitment to deliver new treatment options for patients with bladder cancer.”1
Pfizer’s sasanlimab in combination with BCG improves event-free survival in patients with BCG-naïve
https://www.pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-bcg-improves-event-free
A study of sasanlimab in people with non-muscle invasive bladder cancer (CREST)
https://clinicaltrials.gov/study/NCT04165317
FDA issues refusal to file letter on sBLA for nogapendekin alfa inbakicept
Bladder Cancer Awareness Month: Dr. Kamat highlights the state of bladder cancer care
Cxbladder Triage may help patients avoid unnecessary cystoscopies
Speaking of Urology Podcast: Dr. Ritch and Dr. Katz discuss new bladder cancer management app
UGN-102 positions itself as an alternative to TURBT for low-grade NMIBC
Estimated DOR of 2 years is seen with UGN-102 in LG-IR-NMIBC
609-716-7777
Everything indicates that Real Madrid will experience a significant change on the bench
is getting closer to becoming the new manager of the merengue team
Various sources close to the club confirm that the talks are very advanced
The arrival of a new coach always involves adjustments
Even more so when it comes to a young coach
with fresh ideas and a renewed vision of the game
knows that Real Madrid demands from the first minute
The Arrival of Xabi Alonso at Real Madrid | Getty ImagesAmong the many challenges he will have on the table
Luka Modric has been the soul of the white midfield for years
and technical quality have been his hallmark
has seen his prominence reduced this season
everything indicates that Modric could leave Real Madrid this summer
The possible farewell of Modric poses another puzzle for Xabi Alonso
and the management is already analyzing names to strengthen the midfield
but they still lack that touch of calm and wisdom that Modric provided
A Replacement for Luka Modric Will Need to Be Found | Getty ImagesXabi Alonso will have to make quick and accurate decisions
The transfer market looks hectic for Real Madrid
With the arrival of Xabi Alonso and the possible departure of Modric
The club is clear that it must look to the future
but without forgetting the legacy of its great figures
➡️ Real Madrid
Metrics details
to explore the early steps in gliomagenesis
we utilized conditional gene deletion and lineage tracing in tumour mouse models
coupled with serial magnetic resonance imaging
to initiate and then closely track tumour formation
We isolated labelled and unlabelled cells at multiple stages—before the first visible abnormality
and then through the stages of tumour growth—and subjected cells of each stage to single-cell profiling
We identify a malignant cell state with a neural crest-like gene expression signature that is highly abundant in the early stages
but relatively diminished in the late stage of tumour growth
Genomic analysis based on the presence of copy number alterations suggests that these neural crest-like states exist as part of a heterogeneous clonal hierarchy that evolves with tumour growth
By exploring the injury response in wounded normal mouse brains
we identify cells with a similar signature that emerge following injury and then disappear over time
suggesting that activation of an injury response program occurs during tumorigenesis
our experiments reveal a non-malignant injury-like microenvironment that is initiated in the brain following oncogene activation in cerebral precursor cells
our findings provide insight into the early stages of glioblastoma
identifying a unique cell state and an injury response program tied to early tumour formation
These findings have implications for glioblastoma therapies and raise new possibilities for early diagnosis and prevention of disease
the focus has been on exploring the complex population of malignant and stromal cells that characterize the late-stage tumour
leaving unclear the sequence of events that occur during the early stages of tumorigenesis
attempts to address the identity of tumour-initiating and tumour-maintaining cells directly are limited by clinical and ethical challenges in sampling human tumours at the earliest stages of tumorigenesis
Here we explored tumour development from the earliest stages of initiation by combining GBM mouse modelling with serial magnetic resonance imaging (MRI) and single-cell profiling
Our work provides evidence of systematic and progressive changes in the identity and balance of cellular states between the early and late stages of tumour growth and sheds new light on the origin and development of malignant gliomas
the two mouse models developed high-grade gliomas with high penetrance (>60%) at an average age of 4–8 months
We also generated Sox2creER/+R26td/td (Sox2CET) mice in which the administration of tamoxifen on P3 results in Cre recombination and activation of the tdTomato reporter but no deletion of tumour suppressor genes and therefore no tumours
and colours correspond to the distinct cell populations
but each is highlighting the cells belonging to one of the five sample groups
Colours highlight the cells from each of the five groups (control
Colours correspond to the subtypes identified
Area plot showing the proportion of the individual malignant cellular states in each of the four stages of tumorigenesis
Colours correspond to the malignant cell states
UMAP plots as in a but highlighting the expression of the NCC and Schwann cell markers: Foxd3
our data revealed a high abundance of slow-cycling cells with an NCC-like signature during early gliomagenesis in the adult brain and showed that the relative cellular composition of the tumour evolves continuously from the earliest stages to the time of symptomatic presentation
with colours indicating the cell state of the neighbourhood index cell
and the size corresponding to the number of cells in the neighbourhood
Graph edges depict the number of cells shared between neighbourhoods
The layout of nodes is determined by the position of the neighbourhood index cell in the copy-number-based UMAP
Right: bar plot showing the proportions of the cell states within each neighbourhood
Colours correspond to the cellular states of malignant cells
Same analysis as a but in mid-lesion replicate no
Same analysis as a but in end-point replicate no
a, Top: phylogenetic tree highlighting the clonal generations of the malignant cells in early-lesion replicate no. 1. Generation of each cell node was defined as the step it takes to go from the root node to the cell node (Methods)
Middle: phylogenetic plot as above but highlighting the cellular states of the malignant cells
Bottom: bar plot showing the relative fraction of the distinct malignant cellular states in each of the clonal generations indicated in the above panels
Colours correspond to the malignant cellular states identified in each clonal generation
these findings suggest a model for tumorigenesis in which malignant NCC-like cell states exist as part of a tumour cell hierarchy that evolves with tumour growth
This hierarchy includes a diversity of PC-like states that proliferate and/or differentiate
eventually outnumbering the NCC-like cells as the tumour expands
These findings raise the possibility that the presence of NCC- and MSC-like tumour cells in the adult brain might be associated with the aberrant activation of a normal injury-like response
we first examined whether injury in the normal brain could induce phenotypic states with NCC- and/or MSC-like signatures
Colours on the main panel correspond to the distinct cell types identified in the dataset; colours in the inset panel identify the cells from each of the five sample groups (control
Bar plot showing the relative fraction of the distinct PC types in each time point
these results show that brain injury induces transient MSC- and NCC-like states
these results indicate that the tumour NCC-like cells may regulate the recruitment of injury-like tumour-associated microglia and promote a pro-proliferative signalling network during early tumorigenesis
This suggests that the diversity in PC-like or differentiated-like cells is not a prerequisite for tumour formation
our results indicate that the genetic abnormalities that alter the normal lineage progression of PCs can result in the aberrant activation of an injury-like response that may induce NCC- and/or MSC-like states in mutated cells
as well as lending support to the fidelity of the CNA inference analysis
these results revealed that tumour multiclonality in mouse gliomas is reflected in the spatial organization of genetic clones containing diverse malignant cell states
The malignant NCC-like cells we identified in the tumours show a transcriptional signature that resembles migratory NCCs as well as the neural crest-derived Schwann cell populations
Quantitative analyses of the data support a hierarchical model in which these multipotent NCC-like cells are part of a tumour cell hierarchy that evolves between early and late tumorigenesis and includes a diversity of precursor-like cells that either enter a proliferative state or differentiate and/or die
our experiments revealed that traumatic disruption of cerebral tissue
induces transient NCC- and MSC-like states as part of a normal regenerative response
suggesting the activation of an injury-like process during early tumorigenesis
This is further supported by our findings of injury-associated microglia and OLs during the early stages of tumorigenesis
Although the current findings identify multipotent NCC-like states that could drive the heterogeneity observed during tumour development
this does not implicate or reveal the potential cell-of-origin of malignant gliomas
Our findings suggest that the deletion of GBM-associated tumour suppressors elicits an aberrant regenerative program in which an
unresolved Sox2+nestin+ cell population acquires an NCC-like identity that supports tumorigenesis
tumour-initiating capacity may be shared across a wide population of malignant cell states
Our observations also accommodate the possibility that in some cases
developmental NCCs and MSCs could persist into adulthood and function as stem cell-like populations that support tumour growth
Exploring this will be the focus of future work
although we believe that our tumour mouse models faithfully recapitulate human glioma development
more experiments should be performed in other glioma mouse models
by following tumorigenesis from the early stages to late end-point tumours
our results present a roadmap of GBM initiation and development
Our study uncovers distinct cellular states that exist across the various stages of tumorigenesis as well as the potential role of injury-response mechanisms in driving tumour initiation and progression
The glioma and control mouse models were generated and housed in 12-h dark–light cycle facilities maintained at appropriate temperature and humidity and in which mice had free access to water and chow
The mice were monitored daily and euthanized once they developed end-point symptoms of raised intracranial pressure or focal neurological abnormalities
The mouse experiments were all performed following the ethical and legal regulations
The experiments and animal use protocols were approved by the Animal Care Committees in the different institutions at the University of Toronto
including the Hospital for Sick Children and University Health Network
Tissue processing was performed in the same way for the Sox2eGFP mouse brain injury samples and was followed by cell sorting to separate the live GFP+ and GFP− cells
the nuclei were isolated from sorted cells and processed using the 10x Genomics Single Cell ATAC-seq workflow and following the manufacturer’s protocol (user guide CG000168 Rev A)
5 μl of nucleic suspension was added to the transposition reaction
which was used for the gel beads-in-emulsion (GEMs) generation and barcoding on the 10x Chromium Chip E for PCR amplification
DNA was recovered using Dynabeads MyOne Silane beads
which proceeded to library preparation to add Chromium i7 Sample Index N Set A library barcodes
Libraries were validated on the Agilent 2100 Bioanalyzer to check for size and quantified by quantitative PCR using Kapa Library Quantification Illumina/ABI Prism Kit protocol (KAPA Biosystems)
Validated libraries were pooled in equimolar quantities and paired-end-sequenced on the Illumina Novaseq platform following Illumina’s recommended protocol to generate paired-end reads of 50 bases in length
Spatial transcriptomics was performed on formalin-fixed and paraffin-embedded mouse tissue sections using the 10x Genomics Visium platform and following the manufacturer’s protocols (user guides CG000407 Rev D and CG000409 Rev C)
Mice were prepared for surgery and anaesthetized using isofluorane
The intracranial cannula (Brain infusion kit 3) was implanted at 1.5 mm lateral and 0 mm posterior to bregma
and the saline osmotic pump (Alzet Model 1007D) was implanted subcutaneously following the manufacturer’s instructions
Each osmotic pump was filled with normal saline to infuse the brain at a flow rate of 0.5 µl h−1 for 5 consecutive days
Raw sequencing data from the 30 scRNA-seq samples (Extended Data Table 1) were aligned to the mm10 mouse reference using Cell Ranger (v3.1.0)
Doublets and multiplets were identified by scDblFinder (v1.4.0)
and low-quality cells (percentage of mitochondrial >12%; number of genes detected per cell <800; number of unique molecular identifier (UMI) per cell <500) were removed as part of the quality control process
Seurat (v4.5) was used to integrate and cluster data from all samples together
We used Seurat’s merge function to combine data from all samples together
we used the following: Seurat’s LogNormalize method with a default value of 2,000 variable features; scaling was performed with regression of mitochondrial percentages; rann method for finding nearest neighbouring cells; and principal component analysis (PCA) reduction with the first 30 dimensions
Cell type assignment was based on the differentially expressed gene analysis and using the known cell type markers from the literature
We computed the top differentially expressed markers for each of the clusters compared to all other clusters using Seurat’s Wilcoxon rank sum method with a minimum cell fraction of 0.25 and a minimum fold difference of 0.25
and then ranked them by their fold changes and adjusted P values
The rann method was used to identify k-nearest neighbouring cells
We then annotated the cells on the basis of the differentially expressed gene analysis and using the known cell type markers from the literature
Removing these 205 cell cycle genes was necessary to mask out cell cycle genes expressed at high levels to identify the cycling subtypes
Reclustering revealed six cycling cell types (cycling NSC-
To compute the fractions of cycling and non-cycling cells for each of the precursor-like malignant states (NSC
we calculated the number of cycling and non-cycling cells for each precursor state in each of the samples
The fractions of cycling and non-cycling cells for each PC-like state were calculated as the number of cells over the sum of both cycling and non-cycling cells
We plotted the averages along with their standard errors
gene-level relative CNA profile for each cell
Visualizing the distribution of the relative CNAs
with one bigger peak centring around 1 representing a gene without clear CNAs
which we interpreted as a gain of copy and a loss of copy
one copy of gain or loss should cause a shift of 0.5 in the relative copy number
meaning that the centre of the peak should be around 1.5 for a gain of copy and 0.5 for a loss of copy
Owing to the high level of noise in scRNA-seq data
presenting a smaller one-copy shift than 0.5
we rescaled the inferred CNAs to make the two CNA peaks located around 1.5 and 0.5 before rounding them to integers
we first removed genes without clear CNAs (abs(CNA − 1) < 0.01)
We then identified the two CNA peaks by clustering the CNA values into two clusters using k-means
We then used the centroids of the two clusters to calculate the one-copy shift in the data (mean(abs(centroid − 1))
Then a rescaling factor can be calculated as the fold change between the theoretical one-copy shift (0.5) and the estimated one from the data
we rounded it to integers to calculate the absolute number of copies (round(CNA × 2))
with colour indicating cell state of the neighbourhood index cell
and size corresponding to the number of cells in the neighbourhood
we used phateR to generate two-dimensional (2D) embeddings (PHATE space)
Then we built a spanning tree of different cell types in the 2D PHATE space using slingshot
we first clustered cells into five clusters along the trajectory
and then the cluster-specific maker genes were found using the FinderAllMarkers() function in Seurat
we also used the diffusion map implemented in the R package destiny v3.4.0 to generate the 2D embeddings of the 50 harmony embeddings
and used PAGA in scanpy to summarize the k-nearest neighbours (knn)
All of these methods and others resulted in trajectories with similar topologies between cell states
We used CellChat v1.1.338 for the analysis of cell–cell communication
which was performed separately for each of the four stages of tumorigenesis
We followed the official workflow with default parameters unless otherwise indicated
we loaded the normalized counts into CellChat
followed by the preprocessing steps identifyOverExpressedGenes() and identifyOverExpressedInteractions()
We smoothed gene expression by applying a diffusion process on the protein–protein interaction network implemented in projectData() function
We then ran the computeCommunProb() function for communication analysis with the parameter population.size = FALSE to eliminate possible bias due to cell population size
This resulted in a network of communication strength between all cell states for each of the ligand–receptor pairs that passed the filtering steps
We used the aggregation functions computeCommunProbPathway() and aggregateNet() to determine the communication strength between cell states at pathway and global levels
we evaluated the role of different cell states as senders or receivers on the basis of the out-degree or in-degree of the communication network
implemented in the netAnalysis_signallingRole() function
We conducted a comprehensive evaluation of how well the cell phylogenies can be reconstructed by the pipeline we adopted using simulation data (Supplementary Figs. 7 and 8)
The evaluation pipeline consisted of three parts
The first part consisted of simulating the cell phylogeny and the corresponding CNA profiles
An important consideration is that we are able to see only the living cells on the phylogeny
We truncated the phylogeny to keep only living cells and their CNA profile for downstream analysis
The second part consisted of reconstructing the cell phylogeny based on the CNA profiles of living cells
we also test hierarchical clustering with three different distance measures as the baselines
The third part consisted of evaluating how well the cell phylogeny has been reconstructed from two aspects: the clone identification and the directionality of cell evolution
Our simulation results showed that all four methods can recover the clones reasonably well on the basis of CNA profile
but MEDALT showed better performance in terms of reflecting the directionality of cell evolution
the expected total number of cells N(t) can be expressed as:
in which N0 is the initial number of cells
The interval of time Δt between two adjacent events (the length of the branch in the phylogenetic tree) follows an exponential distribution with mean E(Δt) = 1/(b + d)
it can be a birth with a probability of b/(b + d)
we assumed that the birth and death rates do not change during the evolution
This model is based on a two-component hierarchy involving transitions from a slow-cycling stem cell-like compartment (S) to a more rapidly cycling progenitor population (P)
The simulation is similar to the birth–death model; the difference is that cell division happens in a different way for S cells and P cells
the branching is the same as the classic birth–death model
with an equal probability of being a death or a birth
with high probability (0.8–0.9 for our simulation)
it can also divide symmetrically to self-renewal
we assumed that the birth and death rates for P cells and the probability of symmetrical division for S cells do not change during the evolution
After simulating the whole phylogeny of all cells
we truncated the phylogeny using the function ape::drop.tips() to keep only living cells on the leaf node
with necessary common ancestors to form a complete dendrogram
This truncated phylogeny of living cells was used as the ground truth for downstream analysis
The CNAs in a cell are acquired in two ways: inherited from its parent cell; newly acquired during cell division
We simulated the CNA accumulation on the whole phylogenetic tree we generated
we assume that the number of newly acquired CNAs follows a Poisson distribution with the parameter λ
CNAs can affect contiguous sites and regions in a chromosome
meaning that a gain (or loss) of copy for adjacent genes can happen together
We assumed that the starting position of each CNA was uniformly distributed across the genome
and the number of genes that one CNA affected followed another Poisson distribution (with a mean of 100–200 in our simulation)
CNAs for living cells were selected for downstream analysis
We used four methods to reconstruct the cell phylogeny—MEDALT and hierarchical clustering with three different distance measures of CNAs (namely
the MED and the shortest path distance (SD) on the tree given by MEDALT)
We loaded the tree given by MEDALT into R as an igraph object
visualized it using GGally::ggnet2() and calculated pairwise SD using igraph::distances(mode = ‘all’)
We evaluated the reconstructed cell phylogenies from two perspectives: clone identification and directionality of evolution
We used MEDALT and hierarchical clustering with three different distance measures of CNAs
the MED and the SD on the tree given by MEDALT
visualized it using GGally::ggnet2() and calculated pairwise SD using igraph::distances(mode = ‘all’)
following the developers’ default recommendations
We applied a two-round iterative latent semantic indexing (IterativeLSI) on the 500-base-pair tile matrix
resulting in a 30D embedding space of the genome-wide accessibility profiles
Then we used UMAP to generate a 2D visualization of the IterativeLSI embeddings
Clustering of cells was also conducted in the IterativeLSI space by building a shared nearest-neighbour graph followed by Louvain clustering as implemented in the R package Seurat
Gene activity scores were calculated on the basis of the local accessibility of gene regions
As we have the paired scRNA-seq samples for both scATAC-seq samples
annotation of scATAC-seq data was performed using the label transfer approach implemented in ArchR
open chromatin peaks were called on the basis of pseudo-bulk replicates of different cell types using MACS2
and differentially accessible regions were identified using a Wilcoxon test implemented in ArchR (false discovery rate < 0.1 and fold change > 1.5)
Transcription-factor-binding motifs were annotated using the CIS-BP database
identified using the peakAnnoEnrichment() function implemented in ArchR (Padj < 1 × 10−10) and visualized as a network using Cytoscape
We also conducted differential analysis of gene activity scores using the Wilcoxon test and enrichment analysis of the resulting gene set using enrichR_v3.0 ()
The same computational pipeline and method as for the tumorigenesis atlas were used to remove doublets, and integrate and annotate the ten injury samples (Supplementary Fig. 9a)
The following cutoffs were used to remove low-quality cells: percentage of mitochondrial >12%; number of genes detected per cell <800; number of UMIs per cell <500
We isolated the microglia and OL cells in separate analyses and recomputed their top differentially expressed markers separately
The abundance fractions of the different cell types in the relevant category of cell types (for example
PC types) in each time point were calculated as the number of cells for each cell type over the total number of cells from all the cell types belonging to that category in each time point
We used the R package rstatix (v0.7.0) to compute the one-sided Fisher’s exact tests of the proportions of the cell types in the different time points
we calculated the number of cells in each cell category to construct the contingency table
The function fisher_test() was used to perform the statistical tests
We analysed spot gene expression in Visium data using Scanpy v1.9.3 and Squidpy v1.3.0. For cell type deconvolution within each spot, we used cell2location v0.1.3, using our single-cell mouse datasets as the reference. For mouse Visium samples containing both normal and tumour regions, an initial reference was constructed using the major cell types denoted in Fig. 1c
The resulting analysis successfully delineated tumour from normal regions
corroborating results from both gene expression and H&E imaging
To attain a more detailed deconvolution of cellular subtypes
two distinct references were created for the tumour and normal regions
malignant cells and microenvironment cell types (for example
macrophages and endothelial cells) were extracted
Subtypes labels were used to build the tumour reference
normal brain cell types were utilized to construct this reference
When estimating the reference cell type signatures
the ‘sample ID’ served as the batch_key to mitigate batch effects
the mitochondrial gene ratio and total UMI count were incorporated as covariates to counteract potential biases
we performed the deconvolution separately for tumour and normal regions using their respective references
as all tissues were sourced from tumour regions
the tumour reference was used for deconvolution
To investigate the clonal distribution of tumour cells in the space
This analysis was performed under the assumption that the cells in each of the Visium spots belong to the same clone (that is
Given the small number of cells contained in each spot
we consider this as a reasonable assumption
We selected the reference data for inferCNV with precision
recognizing its crucial role in ensuring result accuracy
we used the normal regions within each slide as the reference
which we can easily distinguish through H&E imaging and scRNA-seq data
We clustered spots on the basis of their RNA profiles
Among the RNA clusters corresponding to normal regions
we earmarked one as the reference and set aside the remaining normal clusters as negative controls
Our analysis using inferCNV revealed no distinct CNVs in these normal region clusters
whereas tumour regions exhibited pronounced CNVs
which consist of late-stage tumours with almost no normal regions
we turned to the normal brain Visium data from the SpatialLIBD Project
we randomly selected two slides from the project as references
Both references yielded congruent outcomes
The same quality control cutoffs as for our atlas were used; Seurat and Harmony were used to integrate
The same computational pipelines as for our atlas were used for computing the top differentially expressed genes and inferring CNAs
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
The following publicly available data analysis packages
software and tools were used in this study and are cited in the text: Cell Ranger (v3.1.0
Squidpy (v1.3.0) and cell2location (v0.1.3)
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Identification of human brain tumour initiating cells
Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model
Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
and Rb pathways induces high-grade astrocytoma in adult brain
A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours
Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages
Outer radial glia-like cancer stem cells contribute to heterogeneity of glioblastoma
Human glioblastoma arises from subventricular zone cells with low-level driver mutations
Mosaic analysis with double markers reveals tumor cell of origin in glioma
A restricted cell population propagates glioblastoma growth after chemotherapy
Single-cell transcriptomics uncovers glial progenitor diversity and cell fate determinants during development and gliomagenesis
The somatic genomic landscape of glioblastoma
Ji, Y. et al. Single cell transcriptomics and developmental trajectories of murine cranial neural crest cell fate determination and cell cycle progression. Preprint at bioRxiv https://doi.org/10.1101/2021.05.10.443503 (2021)
A single-cell molecular map of mouse gastrulation and early organogenesis
Spatiotemporal structure of cell fate decisions in murine neural crest
Requirement for Foxd3 in the maintenance of neural crest progenitors
Schwann cell precursors represent a neural crest-like state with biased multipotency
Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy
Quiescent human glioblastoma cancer stem cells drive tumor initiation
MEDALT: single-cell copy number lineage tracing enabling gene discovery
Neuroepithelial cells supply an initial transient wave of MSC differentiation
Development of mesenchymal stem cells partially originate from the neural crest
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function
Mesenchymal precursor cells in adult nerves contribute to mammalian tissue repair and regeneration
Injury and stress responses of adult neural crest-derived cells
The wound microenvironment reprograms Schwann cells to invasive mesenchymal-like cells to drive peripheral nerve regeneration
Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity
Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery
Interleukin-10 prevents pathological microglia hyperactivation following peripheral endotoxin challenge
Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
A shared disease-associated oligodendrocyte signature among multiple CNS pathologies
Inference and analysis of cell-cell communication using CellChat
Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth
Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner
Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth
Single-cell transcriptomic analysis revealed a critical role of SPP1/CD44-mediated crosstalk between macrophages and cancer cells in glioma
Activated EGFR signaling increases proliferation
and migration and blocks neuronal differentiation in post-natal neural stem cells
HEDGEHOG-GLI1 signaling regulates human glioma growth
Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration
Control of progenitor cell number by mitogen supply and demand
Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens
Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors
Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo
p53 suppresses the self-renewal of adult neural stem cells
Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis
Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity
Evolution of vertebrates as viewed from the crest
Establishing neural crest identity: a gene regulatory recipe
Sox2+ adult stem and progenitor cells are important for tissue regeneration and survival of mice
Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer
a persistent marker for multipotential neural stem cells derived from embryonic stem cells
sensitive and accurate integration of single-cell data with Harmony
Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors
BBKNN: fast batch alignment of single cell transcriptomes
SCANPY: large-scale single-cell gene expression data analysis
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Differential abundance testing on single-cell data using k-nearest neighbor graphs
Visualizing structure and transitions in high-dimensional biological data
Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis
Vidhya, R. Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Dryad https://doi.org/10.5061/dryad.h70rxwdmj (2022)
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This research study was supported by funding from the Canadian Institute of Health Research
with supplemental support from the Ontario Institute for Cancer Research through funding provided by the Government of Ontario
was supported by an Ontario Trillium award from the University of Toronto and the Province of Ontario
We thank the Hospital for Sick Children Foundation
These authors contributed equally: Kui Hua
Developmental and Stem Cell Biology Department
Arthur and Sonia Labatt Brain Tumour Research Centre
European Bioinformatics Institute (EMBL-EBI)
Department of Applied Mathematics and Theoretical Physics
Wellcome Trust-Medical Research Council Stem Cell Institute
designed and performed the experiments and generated the data
performed the analysis of the single-cell data
wrote the manuscript (and all authors provided feedback)
The authors declare no competing interests
reviewer(s) for their contribution to the peer review of this work
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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Twenty-four students from Washington D.C.’s Potomac Job Corp Center recently completed a 40-hour training course on hazardous materials awareness and train-the-trainer as part of IAM CREST’s and the Transportation Communications Union (TCU/IAM)’s Advanced Transportation Training Program
“These young people are just starting out in various trades
and some may even go into the military,” said IAM Resident General Vice President Jody Bennett
who attended the training and met with students
“The IAM and TCU/IAM are proud of them for completing this industry recognized training which teaches safety around hazardous materials they may encounter on their journeys into various careers.”
Students at this job corps site are learning how to be the best candidates for entry level jobs in various trades
these students also get to see the value that unions bring to the transportation careers they are seeking
View photos from the visit here
“This is our first opportunity to work with Job Corps
to train young workers,” said TCU/IAM National President Artie Maratea
“We hope to expand to the other six TSD program sites across the nation soon
We understand the need to teach these workers that hazardous materials can be anywhere on the job
and we want them to be leaders on how to keep themselves and their co-workers safe from harm
especially in the transportation industries.”
Job Corps helps 60,000 young people each year obtain vocational training from the U.S
Over 2 million students have been served since its inception in 1962
because you see that many of them are already leaders that just need a chance to get out there and lead,” said IAM CREST Safety Instructor Barry Eveland
“Having a certification like this shows a prospective employer that they go above and beyond their peers to earn a job opportunity
Several of them already have multiple job offers once they complete the entire program.”
Tanya Galloway wants to be a flight attendant
Her vision board in the hallway is filled with aspirations of a young adult ready to see the world
and is deciding which is the better opportunity
Look for her at an airport in the near future
you may see her running a space port one day
All the students in this class of future leaders are on a launchpad with the countdown clock ticking toward liftoff
Each takes a part of organized union labor with them when they set off on journeys that can lead to places we can probably not even imagine yet
Petersburg Collegiate High School (SPCHS) students have been leading cleanup efforts around the lake on the east end of the St
What began as a community cleanup has now grown into a key priority for the SPCHS National Honor Society and a large-scale community initiative
SPC was asked to participate in a community cleanup of the shoreline of Eagle Crest Lake
Lang Student Success Center and 66th Street
The students enjoyed being part of the process of keeping the lake and the campus beautiful
and began cleaning up the lake shoreline each fall
the initiative provided an opportunity to increase civic engagement
develop strong peer and faculty relationships
and enhance the lake’s overall health
SPC students and science faculty have partnered with Keep Pinellas Beautiful (KPB)
James Bays (President of Stewards of Our Urban Lakes
Petersburg to organize ongoing cleanup events
faculty and local residents—work together to remove trash from the lake
Canoes provided by KPB allow volunteers to access and clean the lake itself
further expanding the project’s impact
students play a vital role in collecting environmental data
assess biodiversity by identifying plant and animal species
Under the guidance of Environmental Science Professor Dr
students measure key water quality indicators such as temperature
Algae growth and microplastic levels are also monitored
These efforts provide students with valuable hands-on experience in scientific data collection and ecosystem analysis
students established four test plots along the shoreline
planting five different species of aquatic plants to enhance biodiversity
demonstrating the long-term ecological benefits of the project
The impact of the Eagle Crest Lake cleanup has been significant
over a thousand pounds of trash have been removed
fostering greater environmental awareness and engagement among students
Participants not only contribute to improving their local environment but also gain valuable skills in scientific research
environmental conservation and community service
and additional volunteer opportunities will be available throughout 2025
and community members are encouraged to participate in upcoming events to support this important environmental effort
For more information or to get involved, contact Associate Dean Stephen Andrasik at andrasik.stephen@spcollege.edu
St. Petersburg College is committed to equal access/equal opportunity in its programs, activities, and employment. For additional information visit www.spcollege.edu/eaeo
Use this link to report accessibility issues on this page.
The Ohio River crest was cresting at more than 60 feet on Monday, bringing the possibility of more flooding in communities along the river, according to the Office of Water Prediction
Forecasters say residents should expect significant flooding in East End
as well as backwater floods in Silver Grove
and riverfront buildings flooded in Aurora
along with additional low-lying roads near the river
and backwater flooding is expected along the Little Miami
The main levels of homes in the East End could also become flooded
List: See what roads are closed due to flooding
The last time the river experienced a crest of 60 feet was in February 2018
the Ohio Department of Transportation started installing 15 floodgates at the Riverfront Transit Center under Second Street to prevent the river from spilling onto Fort Washington Way
Freeze warning for area beginning late Monday nightCincinnatians know the joke: If you don't like the weather
it's no surprise that the National Weather Service office at Wilmington has issued a freeze warning from late Monday night through Tuesday morning
Sub-freezing temperatures are forecast in the lower and middle 20s
In portions of east central and southeast Indiana
Forecasters say that from late Monday night through Tuesday morning
frost and freeze conditions could kill crops
other sensitive vegetation and possibly damage unprotected outdoor plumbing
Be prepared for below-freezing temperatures Tuesday and Wednesday morning
Be prepared to take steps to protect tender plants from the cold
Consider draining in-ground sprinkler systems and covering above-ground pipes
The Ohio River at Cincinnati remained under a flood warning Monday
with forecasters urging residents to use caution if traveling on the roadways
"Turn around, don`t drown when encountering flooded roads. Most flood deaths occur in vehicles," the National Weather Service said in a warning statement on its website
could make getting caught in floodwater even more dangerous
The Cincinnati Police Department says to be sure to obey road closed signage in areas experiencing standing high water for your safety and that of first responders
Road beds may be washed out under flood waters
You do not know the condition of the road under the water
Although the heaviest rainfall has come and gone
forecasters are still warning of high water and flooding impacts into the work week
The weather service says Monday will be sunny before becoming partly sunny in the afternoon
Some cloudy conditions are expected at night and the temperature will reach a low of 25 degrees
Tuesday night: widespread frost after 4 a.m
Wednesday: A slight chance of rain after 2 p.m
Calm wind becoming south 5 to 7 mph in the morning
then rain and possibly a thunderstorm after 2 a.m
New rainfall amounts between a quarter and half of an inch possible
UNDATED (WKRC) - A recent independent study has raised questions about the safety of popular toothpaste brands
This includes well-known names such as Crest
The findings revealed that 65 percent of the tested toothpastes were found to contain arsenic
47 percent had mercury and 35 percent contained cadmium
The presence of these metals was particularly alarming due to their potential health impacts
Mercury and arsenic pose risks to the kidneys
Food and Drug Administration’s current safety thresholds for cosmetics containing toxic metals
which are set at 10,000 parts per billion (ppb)
BRG reported these limits were considered outdated and that Washington State recently enacted a law limiting lead in toothpaste to just 1,000 ppb
The World Health Organization has said that there is no known safe level of lead exposure
But those heavy rains left a swollen Ohio River in Louisville and varying degrees of flooding around much of the state, including hard-hit Frankfort
And as more stormwater rolls into the region from waterways to our east
the high water is likely here to stay for some time
According to the National Water Prediction Service, the Ohio River is expected to crest at 37 feet at the upper portion of the McAlpine Locks and Dam near the Falls of the Ohio
similar to the water levels reached in the 2018 floods
The lower portion of the dam is expected to crest at 68.5 feet
which could pose threats to west and southwest Louisville
Much of River Road was underwater by Sunday
including businesses around the historic Louisville Water Tower
where Louisville EMS said more than 60 people were evacuated Monday from a nearby Candlewood Suites Hotel
and further east toward Harrods Creek and Wolf Pen Branch
Waters are expected to crest in the area Wednesday
with a likelihood it could be among the 10 highest floods in city history
The Kentucky River in Frankfort appeared to have crested as of Monday morning, but Kentucky's capital city was rocked by the waters. Residents were asked to stay home and conserve water if possible as many local businesses were swamped, including the Buffalo Trace Distillery
which expects to remain closed until Thursday at the earliest
Eyes in the region were also watching the Dix Dam closely
Ten of the spill gates on the dam between Mercer and Garrard counties were opened as part of a planned release Sunday
but a miscommunication between officials led Carrollton Mayor Robb Adams to warn residents the gates were accidentally opened and that communities along the Kentucky River should evacuate
Kentucky State Police confirmed the body of Lee Chandler
marking the third death of the flooding event
Andy Beshear confirmed a fourth death in Trigg County
Chandler was swept away while trying to retrieve his boat Sunday
a 9-year-old boy in Frankfort and a 74-year-old woman in Boston
according to the governor and local officials
The governor did not identify the 65-year-old Trigg County man who was killed. But local outlet WKDZ reported the body of David Duncan was found Monday morning in a truck that had been overcome by floodwaters
Beshear also warned an overnight freeze warning was likely Monday night heading into a chilly Tuesday and urged Bluegrass State residents to continue to take precautions as rivers and other waterways near peak levels
you're not just making a bad decision for yourself
you could cause the harm or even death to that next person that comes along," he added
More than 500 state roads were closed at the start of the week due to high waters
Temperatures in Louisville on Tuesday are expected to remain in the mid to upper 40s
before rising back into the upper 50s and lower 60s Wednesday and Thursday
Some precipitation is expected Wednesday night heading into Thursday
In cases of life-threatening emergencies, Beshear said, call 911. For immediate issues that do not put lives at risk, call 502-607-6665 or visit kyem.ky.gov
Emergency management crews from several other states are currently in the commonwealth supporting the National Guard
"Four days of severe storms have brought devastation to so many communities," Beshear said
To all the rescue teams from here in the commonwealth or from other states that have come to aid us
Thanks for answering the call once again."
Stephanie Kuzydym and Killian Baarlaer contributed
Reach The Courier Journal's news team at lounews@courier-journal.com
Celia Peterson a 2019 graduate of The Dalles High School marks her 100 mile marker on the Pacific Crest Trail on Tuesday
2025 — Celia Peterson and Jensen Douillard have hiked more than 100 miles on the Pacific Crest trail since starting the 2,650 mile journey on April 8th
but not without a few bumps in the trail.
said they hiked out to the highway to catch the 11 mile hitch into Julian on Monday morning as they were looking forward to free slice of pie at Mom’s Pie House - a PCT tradition
Meanwhile here at CCCNews headquarters we got a call from Victor Johnson who pointed out that Julian was the epicenter of a 5.2 magnitude earthquake at 10:08 a.m
I immediately called my wife fearing the worst
My wife Peggy contacted the couple who were having their pie
Celia said they were riding in the car toward Julian
and did not even notice the ground shaking
“Welcome to California,” was the popular response to the quake
Even so, the Associated Press was on the story and interviewed Peterson and Douillard in Julian.
Life of Pie - Douillard and Peterson enjoying some Apple Pie at Mom’s Pie House in Julian
“We’re going back on the trail,” Peterson said after having pie
They were both pretty sore after 7 days on trail
The weight of her backpack at about 30 pounds was causing some shoulder discomfort but she was getting used to it.
The two started from the southern terminus of the trail at Campo
California on April 8th and got about 7 miles in the first day.
They’re surviving on ramen, dehydrated potatoes, and freeze dried meals from Bowl & Kettle made by Sarah and Brett Bowlin of Texas who hiked the PCT with my eldest daughter Emily/Zombie in 2022
Their trail names are Mickey D and Fizz.
Jensen said he was surprised how lush the desert was at the start of the trail and they have been stunned by the wide open spaces
Celia said a snake lay sunning itself in the center of the trail and refused to move upon their approach.
The couple said they had to jump the snake to keep moving forward.
They have also been meeting many people along the way and camped with two hikers from the United Kingdom
one from Denmark and one from Finland on Sunday
They have been met with some high winds that have kept the tent flapping at night and they are also adjusting their hiking schedules so that they are traveling in the mornings and evenings to avoid the heat.
“Jensen and I are keeping together and talking a lot,” Celia said
The National Weather Service and the U.S. Geological Survey monitor the water levels of five area rivers and creeks: the Ohio River
These rivers and creeks have gauges that track data and current water levels several times an hour
The data also warns of current or potential flood stages in different areas
In addition, the National Weather Service's Wilmington office monitors the Ohio River at five points: Portsmouth
and what high water and floods could mean for the homes
What is the Ohio River level in Cincinnati?The Ohio River is set to crest at just above 60 feet on Monday, bringing the possibility of more flooding in communities along the river, according to the Office of Water Prediction
The Ohio River's level is monitored from the Roebling Bridge near downtown Cincinnati. The river's action stage is at 40 feet
flooding encroaches Riverbend Music Center
increasing sections of Kellogg Avenue from east of Delta Avenue upstream to near Coney Island and Eight Mile Road are flooded
as well as parts of Humbert Avenue in Cincinnati's East End
as well as Riverside Park off of River Road
List: See which roads are closed due to flooding in the area
forecasters say residents should expect significant flooding in East End
The moderate flood stage begins at 56 feet
and the major flood stage begins at 65 feet
the NWS states that the river level is supposed to fall below the flood stage by Friday
The Great Miami River is monitored at several points as it travels from Middletown to Hamilton and through western Hamilton County
The river's depth can vary greatly based on the location
the action stage begins at 73 feet and the flood stage is at 75 feet
The river rose to 73.5 feet on Saturday morning
but has since fallen to 72.4 feet on Monday morning
The river level will continue to fall throughout the week
The river level rose to 23.26 feet on Saturday
but has since fallen to 20 feet on Monday morning
flooding occurs along Harrison Avenue east of the river
Flooding also occurs downstream of Miamitown in Miami and Whitewater Townships
Depending on river crests coming down the Whitewater River
Lawrenceburg Road may flood between Miamiview Road and U.S
and between Suspension Bridge Road and Stephens Road
The Little Miami River is monitored at several points: Milford
Perintown and near South Lebanon in Warren County
In South Lebanon
The river is currently below the action stage at 13.9 feet as of Monday morning
In Perintown
The river is currently below the action stage at 15.7 feet as of Monday morning
and will drop to 5.8 feet by Friday afternoon
In Milford
The river is currently below the action stage at 12 feet as of Monday morning
The water level for Mill Creek at Evendale is often under eight feet
The action stage begins at nine feet; the minor flooding stage at 12 feet and the moderate flooding stage at 14 feet
The river level is currently at 7.49 feet but rose to 11.42 feet on Friday
lowland flooding of the Mill Creek floodplain occurs
with water approaching some buildings along the creek
The Licking River is monitored in Falmouth
where the depth is typically under 10 feet
It runs north through Pendleton County as the boundary between Kenton and Campbell counties
The river's action stage begins at 23 feet
at which point low-lying areas along the river near Falmouth begin to flood
where basement flooding will begin along Water Street in Falmouth
and flooding begins along a low area of Route 22
Lowland flooding will be expected in Butler and Falmouth
which is considered the moderate flood stage
This is when flooding of low-lying streets near the river in Falmouth will worsen
and flooding will be the worst along Kentucky 22
Main Street will begin to flood near the river
Flooding along Shelby Street and State Route 22 east of Falmouth will worsen
Flooding will also begin along Riggs Street
What does it mean when a river crests?A "crest" is the highest level or elevation of a river during a specified storm event, per the NWS
it is the highest level at which a river rises before it goes down
The Ohio River is set to crest at just above 60 feet on Monday.