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Monthly Archives: June 2022
An Experimental Gene Therapy Changed His DNAAnd His Hair Color – The Atlantic
Posted: June 24, 2022 at 9:50 pm
In October 2019, Jordan Janz became the first person in the world to receive an experimental therapy for cystinosis, a rare genetic disease. The treatment was physically grueling. Doctors extracted blood stem cells from Janzs bone marrow and genetically modified them in a lab. Meanwhile, he underwent chemotherapy to clear out the remaining faulty cells in his bone marrow before he got the newly modified ones. The chemo gave Janz sores in his mouth so painful that he couldnt eat. He lost his head full of pale-blond hair.
But Janz, then a 20-year-old from Alberta, Canada, had signed up for this because he knew that cystinosis was slowly killing him. The mutated gene behind this disease was causing toxic crystals of a molecule called cystine to build up everywhere in his body. He threw up constantly as a kid. Visible crystals accumulated in his eyes. And his kidneys were now failing. Cystinosis patients live, on average, to 28.5 years old.
Fortunately, the experimental gene therapy seemed to work; Janz began to feel better. His hair grew back in a stubble, but to his shock, it came in a different color: dark, almost black. In the two and half years since, his hair has settled into a dark blond, which is still markedly different from the almost white blond of before. My girlfriend actually said the other day that she feels like shes dating a different person, Janz told me.
Of all the things the experimental gene therapy was expected to altersuch as the severity of his cystinosis symptomshair color was not one of them. That was very surprising, Stephanie Cherqui, a stem-cell scientist at UC San Diego and the principal investigator of the gene-therapy trial, told me. But as she and her colleagues dug into the literature on the disease, they found that darker hair wasnt a sign of something going awry; instead it might be a very visible sign of the gene therapy working.
Doctors had observed years ago that cystinosis patients tend to be paler than their families. Manythough certainly not allhave blond hair and pale skin. One study in mice found that the gene thats mutated in cystinosis patients normally plays a role in the production of the dark-brown pigment melanin. Janz had always been a bit self-conscious about how pale he was. His whole family is pretty pale, Janz said. But I'm, like, a whole different paleor I was. The hair change, as far as hes concerned, was a nice surprise.
But how did genetically modifying his blood cells change his hair color? While the mutation that causes cystinosis affects virtually every cell in his body, gene therapy did not change the DNA of every cell in his body, only a tiny fraction of them. Scientists chose to genetically tweak blood stem cells because they have a special ability: Some eventually become white blood cells, which travel to all different parts of the body, Jeffrey Medin, who studies gene therapy at the Medical College of Wisconsin, told me. White blood cells normally go into all our different tissues and organs to patrol for pathogens.
Janzs new white blood cells were genetically modified to express the gene that is mutated in cystinosis, called CTNS. Once they traveled to his eyes, skin, and gut, the white blood cells began pumping out the missing protein encoded by the gene. Cells in the area began taking up the protein and clearing away long-accumulated cystine crystals. In Janz, the anti-cystine proteins from his modified blood cells must have reached the hair follicles in his skin. There, they cleared out the excess cystine that was blocking normal melanin production, and his hair got darker. The same phenomenon has played out in other people: So far in the gene-therapy trial, four of the five patientsall of whom are whitehave gotten darker hair. (The fifth patients hair is just starting to grow back post-therapy.) The investigators have since added hair biopsies to the trial in order to track the color changes in a more systematic fashion.
The sudden hair-color changes were surprising to Cherqui and her colleagues, but they are consistent with the role of the cystinosis gene in hair pigments, says Robert Ballotti, a melanin researcher at the French National Institute of Health and Medical Research. But he has also found that pigmentation and cystinosis can interact in unexpected ways. Not all people with cystinosis are pale, and in particular, Black patients tend not to have skin or hair that is any lighter. Maybe there is not a strict correlation between the gravity of the disease and pigmentation, Ballotti says.
Hair color is one way in which patients in the clinical trial are teaching scientists about the full scope of the CTNS gene, which is still not fully understood. Cherqui had helped discover the gene, as a graduate student more than 20 years ago, and her research has hinted at other functions for it in cell growth and survival, too. More and more, we understand that there are many functions of the protein that we didn't know, she said.
Thats why patients on the standard treatment, a drug called cysteamine, still get sicker and die of their disease, Cherqui said. Removing cystine is not enough. It doesnt help that cysteamine has some pretty nasty side effects: It causes stomach pain, nausea, and diarrhea. When Janz was very young, he needed a stomach tube to get the medication around the clock. Cysteamine also has a rotten, fishlike smell. I had a lot of difficult times as a younger kid, says Jacob Seachord, another patient in the trial whose hair went from blond to brown. I smelled really bad from medication, so I didn't make a lot of friends.
Gene therapy actually replaces the missing protein, theoretically filling in all of its functions, known and unknown. All five patients in the gene-therapy trial have gone off their oral cysteamine, and preliminary data show they now have fewer cystine crystals in their eyes, skin, and gut. Their vision has gotten slightly better, too. But improvements in kidney function are more elusive. Seachord had a kidney transplant before the gene therapy and is doing well. Janz had advanced kidney disease before the trial, and he will need a kidney transplant in a few months.
For adults with cystinosis, Cherqui said, it may be too late for gene therapy to help their kidneys. They have already accumulated a lifetime of kidney damage from cystine. Gene therapy cant reverse the damage thats been done, but we can correct it going forward, Medin said. We can stop progression. In diseases like cystinosis, patients may have to get gene therapy at a young age, probably before 10, Cherqui said. If it works, a future kid who has cystinosis might be cured through gene therapypreventing them from needing a lifetime of cysteamine or a kidney transplant. And it just might change their hair color, too.
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An Experimental Gene Therapy Changed His DNAAnd His Hair Color - The Atlantic
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DNA testing leads to arrest of Oklahoma woman accused of killing her baby – KOKI FOX 23 TULSA
Posted: at 9:50 pm
CHOCTAW COUNTY, Okla. Some readers might find details from this investigation disturbing.
Agents with the Oklahoma Bureau of Investigation have arrested a Choctaw County woman in connection to a nearly 30-year-old cold case.
53-year-old Meaonia Michelle Allen turned herself in this month, fulfilling an outstanding warrant for first-degree murder with deliberate intent. A judge denied Allen bond.
Investigators say Allen killed her newborn baby in 1993 and dumped the body in rural Choctaw County. At the time, the Choctaw County Sheriffs Office contacted OSBI for assistance. An autopsy revealed that the baby was born alive and was killed after its throat was slashed.
Baby Does case went cold after nearly three decades. In 2020, an OSBI agent worked with the Cold Case Unit to submit the babys DNA to Parabon Nanolabs, a company that specializes in using genetic material to solve crimes.
The results gave investigators leads, which pointed them in Allens direction. After additional testing, Allen admitted to giving birth to the baby. She also admitted to killing the infant.
At the time of babys birth, Allen was working at a daycare center. She did not tell anyone about the pregnancy.
The synergy between our agents and criminalists to solve cold cases, especially those with an unidentified victim, is to be applauded, said Ricky Adams, OSBI Director. Identifying the use of genetic genealogy as a tool and the work of Parabon and our internal genealogy specialist provided significant leads in this disturbing case. Baby Doe can now be properly laid to rest and his killer will be held accountable.
2022 Cox Media Group
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DNA testing leads to arrest of Oklahoma woman accused of killing her baby - KOKI FOX 23 TULSA
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Ancient DNA points to where the Black Death began – Ars Technica
Posted: at 9:50 pm
Spyrou et al. 2022
In 1338 and 1339, people were dying in droves in the villages around Lake Issyk-Kulin whats now northern Kyrgyzstan. Many of the tombstones from those years blame the deaths on a generic pestilence. According to a recent study of ancient bacterial DNA from the victims teeth, the pestilence that swept through the Kyrgyz villages was Yersinia pestisthe same pathogen that would cause the devastating Black Death in Europe just a few years later.
In just five years, bubonic plague killed at least 75 million people in the Middle East, northern Africa, and Europe. Known as the Black Death, the cataclysm of 1346-1352 is still the most deadly pandemic in human history. But the Black Death was only the first devastating wave of what historians call the second plague pandemic: a centuries-long period in which waves of Y. pestis periodically burned through communities or whole regions. When English diarist Samuel Pepys wrote about the Great Plague of London in 1666, he was describing a later wave of the same pandemic that began in the mid-1300s with the Black Death. Centuries of life with the reality of the plague actually shaped the genetic diversity of modern European populations.
And like every pandemic, the second plague pandemic had to start somewhere.
Today, we know that the second plague pandemic reached Europe around 1348 aboard ships arriving in Italy from a Genoese trading colony called Kaffa (now the city of Theodosia) on the Black Sea. But the pandemic was already well underway by the time it spread to Europe.
Based on what we know about the ecology of Y. pestis, which spreads through the bites (and vomit) of infected fleas, historys most devastating pandemic began when fleas jumped from their usual hostswild rodents such as marmotsto humans. Researchers have used historical records and genetic evidence to try to pinpoint where and when that spillover happened. So far, though, estimates span the whole breadth of Asia and a period of at least 150 years.
Two villages in northern KyrgyzstanKara-Djigach and Buranaare compelling places to look. The timing fits; an unnamed pestilence killed unusually large numbers of people in the area just a few years before the Black Death struck Europe. And the location also makes sense; the area around Lake Issyk-Kul, called the Chy Valley, had trade connections across Eurasia, making it a perfect crossroads for people, goods, and infectious disease.
Spyrou et al. 2022
To test the idea, archaeologist Maria Spyrou of the Max Planck Institute for Evolutionary Anthropology and her colleagues needed to find out what had actually killed the victims of whatever was spreading in 1338-1339. So they sampled tissue from the teeth of seven pestilence victims and sequenced all of the DNA present in the teeth. That included not only human DNA from the victims but also DNA from bacteria they were carrying when they died.
When you die with a bacterial infection raging in your bloodstream, those bacteria leave their DNA and proteins behind in parts of your skeleton, especially bone marrow and tooth pulp. Archaeologists have used that fact to find ancient plague DNA at sites across Eurasia and recently to diagnose tuberculosis in a casualty of Mt. Vesuvius 79 CE eruption.
In Kyrgyzstan, Spyrou and her colleagues found segments of DNA from Yersinia pestis in the teeth of three people buried in the cemeteries around Lake Issyk-Kul; their tombstones said they had died during 1338 and 1339. Thats enough to link the previously unnamed 1338-1339 pestilence to the plague.
Spyrou et al. 2022
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Ancient DNA points to where the Black Death began - Ars Technica
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S3FOOD’s DNA and blockchain technology cancels food fraud in extra virgin olive oil – Food Ingredients First
Posted: at 9:50 pm
24 Jun 2022 --- A team of biotechnology and blockchain specialists in Greece are using olive oil DNA to generate a fraud-proof genetic barcode for each bottle. With funding from European research and innovation project S3FOOD, the move is expected to minimize food fraud across extra virgin olive oil (EVOO).
The digital tool will safeguard the authenticity and traceability of EVOO from the field. For producers, it means cheaper imitations will no longer undercut the value of high-end products.
Consumers can trust that the EVOO in the bottle lives up to the designation on the label and is safe to consume.
Biodiversity benefits and beyondAs authentic EVOO gains the recognition it deserves, growers will have a greater incentive to protect the biodiversity of olive tree varieties.
The digital tool will safeguard the authenticity and traceability of EVOO all the way from the field.Stelios Arhondakis is CEO of BioCoS, which is working with technology partner InTTrust to develop the anti-fraud traceability tool DNAblockchain.
The high risk of fraud in the olive oil industry is very much related to the products economic value, fragmented supply chain and liquid nature. A recent study has found that the value of a premium EVOO may be reduced by 50%, he says.
Olive oil fraud takes many forms. In 2019, for example, Europol seized 150 metric tons of sunflower oil, which the label claimed to be olive oil. Another case involved 47 millers, two bottlers and traders who sold oil with a fake EVOO Protected Geographical Location (PGI) label.
Traceability from tree to consumerBioCoS is establishing DNA profiles for specific olive varieties used to produce EVOO to counter the problem. One type Koroneiki accounts for around 60% of Greek EVOO production.
An intelligent data processing platform uses DNA data to verify the varietal authenticity of EVOO. This information is then integrated into a blockchain system along with other data, such as quality characteristics, the location of the olive grove and the quantity of EVOO produced.
The whole traceable story will be available to consumers via a QR code on the EVOO bottle.
Blockchain is already widely used in the olive oil sector to track and trace each lot number from the oil manufacturer to the consumer. However, the limitation of this approach is that it ensures only the traceability of the bottle not its content.
DNA-blockchain bridges this gap, making it impossible to mix olive oil with other varieties or other types of vegetable oil without being discovered. So, if you add 3-5% olive oil from a Greek variety to an Italian product, you would be able to trace it via DNA analysis. That gives complete transparency, Arhondakis says.
In addition to the benefits for commercial brands and food safety, the DNA data can be used to create a geo-genetic map of olive growers producing EVOO. Arhondakis believes this could become an essential resource for future efforts to improve the sustainability of olive cultivation and mitigate climate change risks.
Edited by Elizabeth Green
To contact our editorial team please email us at editorial@cnsmedia.com
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S3FOOD's DNA and blockchain technology cancels food fraud in extra virgin olive oil - Food Ingredients First
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U.S. Government Guidance Permits DNA Traceability and Isotopic Testing as Evidence under Uyghur Forced Labor Prevention Act – Business Wire
Posted: at 9:50 pm
STONY BROOK, N.Y.--(BUSINESS WIRE)--Applied DNA Sciences, Inc. (NASDAQ: APDN) (the Company), a leader in cell-free, enzymatic DNA production, has been increasing its engagement with all stakeholders in anticipation of the June 21, 2022, effective date of the rebuttable presumption standard under the Uyghur Forced Labor Prevention Act (UFLPA) signed into law on December 23, 2021. Under the UFLPA, all imports that originate from China's Xinjiang Uyghur Autonomous Region (XUAR) or otherwise use Uyghur or other minorities for forced labor in China, are excluded from entry into the U.S. by the Customs and Border Protection agency (CBP) of the Department of Homeland Security (DHS).
On June 17, DHS issued its much-anticipated Implementation Strategy (the Strategy) for the rebuttable presumption standard under the UFLPA. In this new report, DHS has, for the first time, identified DNA traceability and isotopic testing - both central components of Applied DNAs CertainT authenticity platform - as evidence that importers may present to potentially prove that items do not originate in XUAR or may have benefitted from forced labor.
The UFLPA seeks to insulate U.S. companies and consumers from complicity in forced labor practices in XUAR, which produces nearly 20% of global cotton1. Commercially available for almost a decade, Applied DNAs CertainT platform is a multi-layered textile traceability solution that offers proof of product origin, authenticity, and sustainability.
Catalyzed by the imminent implementation of the UFLPA, Applied DNA is acquiring DNA traceability and isotopic testing clients intent on establishing proof of origin to comply with the UFLPA in the near-term with the long-term objective of securing their global supply chains using CertainT. Louis Dreyfus Company B.V., the Companys cotton merchant partner, recently received a request to ship the first quantities of traceable tagged cotton that is directly attributable to the UFLPA.
In GFY21, CPB used its forced labor authority to detain almost 1,500 shipments with a value of almost $500 million. The Biden Administrations budget request for GFY23, which begins on October 1, 2022, calls for $70 million to implement the UFLPA, to hire 300 additional CBP inspectors, and screen 11.5 times as many shipments for forced labor violations as is being undertaken currently.
CertainT is a 100% American solution that is unique in its ability to offer multiple traceability solutions, including DNA traceability and isotopic testing that are both cited (see page 49 in the link) in the Strategy. We believe that the high bar established by the UFLPA with its documentary and supply chain management requirements place a burden on importers that cannot be adequately met by fungible reporting frameworks, such as conventional paper- or electronic systems, stated Dr. James A. Hayward, president, and CEO, Applied DNA.
Coming on the heels of Customs and Border Protections budget request to fully implement the Strategy, we are pleased to see agreement at the regulatory level as a precursor to potentially broader industry adoption, continued Dr. Hayward. As a U.S.-based company, we applaud the imperative with which the Strategy is moving federal law towards action and, not only for its potential to be transformative to our supply chain security business, but also to deliver clear societal and ethical benefits to the American consumer. With the 2022 cotton ginning season soon upon us, we stand ready to deliver DNA-tagged American cotton to meet brand demand driven by the UFLPA.
Andrew Samet, principal at trade consulting firm Sorini, Samet & Associates and textile lobbyist for Applied DNA, said, It is clear from the new strategy document that Homeland Security officials and others in the U.S. government recognize that documentary traceability is insufficient. Technology solutions proving origin, such as DNA tagging and isotopic analysis, are for the first time being referenced and are the emerging framework both for authentication and enforcement forced labor is a key driver for this secular change now officially underway.
Learn more about the UFLPA: https://www.dhs.gov/uflpa
Footnote:
About Applied DNA Sciences
Applied DNA is commercializing LinearDNA, its proprietary, large-scale polymerase chain reaction ("PCR")-based manufacturing platform that allows for the large-scale cell-free production of specific DNA sequences.
The LinearDNA platform has utility in the nucleic acid-based in vitro diagnostics and preclinical nucleic acid-based drug development and manufacturing market. The platform is used to manufacture DNA for customers as components of in vitro diagnostic tests and for preclinical nucleic acid-based drug development in the fields of adoptive cell therapies (CAR T and TCR T therapies), DNA vaccines (anti-viral and cancer), RNA therapies, clustered regularly interspaced short palindromic repeats (CRISPR) based therapies, and gene therapies.
The LinearDNA platform also has non-biologic applications, such as supply chain security, anti-counterfeiting and anti-theft technology. Key end-markets include textiles, pharmaceuticals and nutraceuticals, and cannabis, among others.
Leveraging its deep expertise in nucleic acid-based technologies, the Company has also established safeCircle, a high-turnkey solution for population-scale COVID-19 testing. safeCircle is designed to look for infection within defined populations or communities utilizing high throughput testing methodologies that increase testing efficiencies and provide for rapid turn-around-times.
Visit adnas.com for more information. Follow us on Twitter and LinkedIn. Join our mailing list.
The Company's common stock is listed on NASDAQ under the ticker symbol 'APDN,' and its publicly traded warrants are listed on OTC under the ticker symbol 'APPDW.'
Applied DNA is a member of the Russell Microcap Index.
Forward-Looking Statements
The statements made by Applied DNA in this press release may be forward-looking in nature within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Forward-looking statements describe Applied DNAs future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to its history of net losses, limited financial resources, limited market acceptance, our unknown ability to penetrate key markets, our ability to successfully enter into commercial contracts for the implementation of our CertainT platform, the uncertainties inherent in research and development, our unknown ability to provide isotopic testing if our agreement with Isotech Labs is terminated, and various other factors detailed from time to time in Applied DNAs SEC reports and filings, including our Annual Report on Form 10-K filed on December 9, 2021, its Quarterly Report on Form 10-Q filed on February 10, 2022 and May 12, 2022, and other reports it files with the SEC, which are available at http://www.sec.gov. Applied DNA undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date hereof or to reflect the occurrence of unanticipated events, unless otherwise required by law.
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23andMe handles tests for ancestry and health risks with respect – San Francisco Chronicle
Posted: at 9:50 pm
Sophia Majeed, principal clinical scientist and project team lead in the 23andMe Therapeutics group, knows how volatile and potentially controversial the biotechnology field is. The company, which has 579 employees, has been through a couple of contentious rounds with the FDA over whether its products are safe medical devices. Theres also the ethical question of what 23andMe does with the data its collected from people after theyve received their DNA results.
For Majeed, the workplace has to be a safe and secure environment. 23andMe workplace culture encourages people to speak out and be their authentic selves, Majeed said. Our CEO, Anne Wojcicki, sets the tone by encouraging people to have difficult conversations, and she doesnt shy away from responding to tough questions.
The San Francisco Chronicles Top Workplaces in the Bay Area competition honors the best workplaces in the Bay Area, as recognized by their employees. This is the 13th year Energage has surveyed Bay Area employees and its first year working with The San Francisco Chronicle.
Wojcicki founded the Sunnyvale-based 23andMe in 2006 with Linda Avey and Paul Cusenza. Avey and Cusenza are no longer with the company. The direct-to-consumer DNA testing company enables consumers to test for ancestry and health risks through genetic information obtained from saliva samples. It ranked second among large companies in the 2022 Bay Area Top Workplaces survey.
The 23andMe lab analyzes the genetic information in the saliva and digitally returns the results to the buyer. There are three levels of testing kits (Ancestry and Traits, Health and Traits, and 23andMe+ Membership), and the process could eventually unlock genetic information that will predict certain illnesses or help generate therapies and cures. The company is named for the 23 pairs of chromosomes in a normal human cell.
I appreciate working here, not because there arent things that can be improved, but because we value each others humanity, and we acknowledge that we must continue to work to be the best versions of ourselves, Majeed said.
That sentiment is echoed by employees in the survey:
I feel that I am challenged to grow and do my best work while working on interesting projects that positively impact our customers lives. I am fully utilized doing work that is meaningful to myself and others.
I trust Anne, the CEO, to lead by example. I care deeply about my colleagues and enjoy working with them. I feel valued and included. My manager is supportive and helpful. When I disagree with a direction, I feel encouraged to speak up and heard if I do. Im excited about the future. Most importantly, I believe in the work were doing and value how impactful and important it is.
My manager provides feedback and support as problems arise, identifies opportunities for me to grow, and has given me responsibilities that have encouraged skill building. Most importantly, my manager has built a strong and trusting relationship with me, which helps me feel like I can try new things and fail without danger of retaliation.
To me, workplace culture determines social norms and defines acceptable behaviors at work. It reflects the core values of the company and senior leadership.
Majeed has seen the company grow not just in size but in understanding how to grow in a way that supports its employees as well.
I am surprised most by the cultural evolution at 23andMe in the last few years, Majeed said. I have seen our commitment to authenticity manifest in a more self-aware and compassionate culture; one that values feedback, self-improvement and honesty.
More Top Workplaces 2022: Large
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TikTok couple Carley and Mercedes doing DNA test to see if theyre related – Dexerto
Posted: at 9:50 pm
TikTok couple Carley and Mercedes have revealed theyre doing a DNA test after finding out that they may be related to each other.
When looking for a relationship, nearly everyones worst nightmare is accidentally falling in love with a long-lost family member.
But, what if you fall in love with someone and dont find out that you may be related until months down the line?
TikTok creators Carley and Mercedes are going through just that, revealing that theyre doing a DNA test after finding out they may be half-sisters.
In early June 2022, Carley and Mercedes posted a video to their joint TikTok page that after two years of dating each other they learned their moms both slept with the same guy.
Due to that, they realized that they might be half-sisters.Their story quickly went viral, leading to millions of views.
(Click here if TikTok doesnt load)
Should we take a DNA test? #siblingsordating #fyp #foryou #wlw #xyzbca
original sound szasgrandchildren
After a few days and thousands of comments saying they should go ahead with a DNA test, Carley and Mercedes posted a video revealing that they ordered one.
However, it will take a few weeks to get the results back.
(Click here if TikTok doesnt load)
Reply to @kutfeminist what do we do lol #fyp #foryou #xyzbca #wlw #siblingsordating
original sound Carley&Mercedes
While Carley and Mercedes havent explicitly said how they feel about possibly being sisters, viewers have been quick to share their thoughts.
Many users explained that they do look like siblings, and could even be twins, while others have mentioned theyre not even sure how theyd react to the situation.
Another hot topic in the comments is whether or not the two should stay together if they do find out theyre related. Viewers are split between what theyd do in Carley and Mercedes shoes with many explaining that theyd stay together.
Either way, its going to be a few more weeks until they find out the results and well be sure to update you when that time comes. In the meantime, head over to our TikTok hub to check out more viral trends and other news.
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TikTok couple Carley and Mercedes doing DNA test to see if theyre related - Dexerto
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Why New Orleans Saints are glad coach Dennis Allen is ‘keeping the DNA the same’ – New Orleans Saints Blog- ESPN – ESPN
Posted: at 9:50 pm
METAIRIE, La. -- Dennis Allen's transition to the New Orleans Saints' head coaching job has been a smooth one by all accounts.
Well, mostly.
Were such creatures of habit, said the Saints former defensive coordinator, who confessed to one particular misstep from a few weeks ago. I left the locker room and went up to my office, and I just walked up the back way and down the hall and walked into what is now [co-defensive coordinator] Ryan Nielsens office. And I was like, Oh damn, I just walked into the wrong office.
He was in there, and I started up some sort of conversation and acted like I needed to talk to him. And then at the end, I was like, I gotta admit something: I really just came to the wrong office.'"
To be fair, though, Allen has made a point of trying to keep things as normal as possible so far this offseason.
The vibe has been much different than it was when Allens mentor, Sean Payton, first arrived in New Orleans 16 years ago and did all he could to change the culture. Payton made tweaks to just about everything, down to signs hanging in the locker room and jersey colors at home games.
Allen, on the other hand, is proud of the culture he helped Payton and much of this current Saints coaching staff and roster build over the course of five straight winning seasons from 2017 to 2021 before Payton decided to step away from the job in January.
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Why would I change things just to change them? Allen said. Weve done a lot of good stuff around here. So youre gonna see a lot of the same stuff.
Now, the way I present the message may be just a little bit different than the way Sean presented it ... kind of putting my own flair on it.
Players and coaches seem to widely appreciate that approach from the 49-year-old Allen, who is trying to find the success in his second head coaching stint that eluded him when he struggled to an 8-28 record with a much less established Oakland Raiders from 2012 to 2014.
Thats huge, just keeping the DNA the same, running back Mark Ingram II said. Its not like its a full rebuild here. We have a team that can make a lot of noise and make a run at it. Obviously, we have to improve and get better and gel as a unit. But I think keeping the DNA of the team, the bloodline of the team, the culture of the team the same is huge.
It helps that everyone -- including offensive players like Ingram -- has seen Allens results on the defensive side of the ball. Under Allens watch, the Saints have ranked fourth in the NFL in both yards allowed and points allowed over the past three seasons. Last December, they became the first team to shut out Tom Brady in 15 years with a 9-0 win on the road against the Tampa Bay Buccaneers.
Although the Saints missed the playoffs at 9-8 in an injury-ravaged 2021 season, their 58 regular-season wins over the past five years rank second in the NFL to only the Kansas City Chiefs.
Even players who just joined the Saints in free agency, like safety Tyrann Mathieu and receiver Jarvis Landry, spoke about being attracted by the established culture in New Orleans -- despite the head coaching change.
The level of consistency is nice. Its something that you rely on. Its something you already trust, defensive end Cameron Jordan said. [Allen is] someone we already trusted. So when you say, Hey, this is for the better of the team, you believe that. Its not like a new guy coming in saying, Hey, this is how were gonna run the team and youre like, Damn, do I buy in or not buy in?
You know what our defense is about, and that immediately brings credibility.
That consistency is felt throughout the coaching staff, where Allen retained longtime offensive coordinator Pete Carmichael Jr. and promoted assistants Nielsen and Kris Richard to the roles of co-defensive coordinator. The biggest staff change the Saints made this offseason was rehiring former Buffalo Bills and Jacksonville Jaguars head coach Doug Marrone as offensive line coach -- after Marrone previously served as Paytons offensive coordinator from 2006 to 2008.
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Allen was also part of Paytons original staff from 2006 to 2010, including the Saints Super Bowl-winning 2009 season, before he became the Denver Broncos defensive coordinator in 2011 and Raiders coach in 2012. Allen returned to New Orleans in 2015.
What we do works and what we do is effective. And lets be honest, Dennis has been a part of developing that, said assistant offensive line coach Zach Strief, who was a rookie when Payton and Allen first arrived in 2006. [Allen] has been a big part of building the culture and the structure. So even though Sean was the head coach, some of it might have come out of [Allen's] brain.
The most noticeable change players and coaches pointed out was a slightly enhanced attention to detail. Not that Payton didnt sweat the small stuff -- he absolutely did -- but Allen is approaching everything with fresh eyes, including meeting times and practice drills.
DAs always been about the minutiae, and its been interesting to see him attack with that same idea on the offensive side that everything needs to be exact, said Jordan, who said he has so far resisted the urge to poke fun at Allen for anything -- or even to complain when the now-impartial head coach doesnt credit the defense for enough sacks in practice.
Im just trying not to get on his nerves, said the often-rambunctious Jordan -- who admits he may have some firsthand experience with that.
I will fall in line and say Sir, yes sir ... for the time being.
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Why New Orleans Saints are glad coach Dennis Allen is 'keeping the DNA the same' - New Orleans Saints Blog- ESPN - ESPN
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Championship DNA powered NK baseball to another title – The Independent
Posted: at 9:50 pm
PROVIDENCE Surely the game-tying home run would be too difficult to come back from.
But it wasnt.
The closer who hadnt thrown a single pitch all year couldnt possibly escape this jam.
But he did.
The North Kingstown High School baseball team has made a habit of meeting every challenge the last two years. Pitching, defense, and timely hitting have been bolstered by an amazing ability to keep fighting. The last two examples were particularly remarkable and they allowed the Skippers to capture their second consecutive state championship with a sweep of Bishop Hendricken this past weekend.
Its team over talent, head coach Kevin Gormley said. Youve got to play the game. These guys, I just told them, theyre the toughest [players] Ive ever coached. Their mental toughness is second to nobody Ive ever coached. A couple of times, they could have folded. They just come back. They dont stop.
It has become a trademark. There was the steady grind required in 2021, when the Skippers were a middle-of-the-road team that caught fire in the postseason and won the state title, with some bumps along the way. They maintained their lofty standards this year, but their quest for a repeat could have ended before it began. They needed a late rally to win their playoff opener. They also fell behind in a semifinal series game. In the finals, they had to scratch and claw to hang on to a 1-0 series-opening win.
The hurdles that popped up in game two of the championship series were the most significant yet, but the Skippers simply upped the ante right along with the stakes. When Hendricken star Brandyn Durand tied the game with a lightning strike of a home run in the bottom of the seventh inning, the Skippers immediately responded with four runs. And when the Hawks loaded the bases with nobody out in the bottom of the eighth, T.J. Gormley went to the mound for the first time all season. The senior stopped the rally in its tracks to seal a 10-7 win.
Its unreal. Im higher than cloud nine right now, T.J. Gormley said. That was such a hard-fought game. That was the hardest game weve played in all year. Im so proud of us. We fought adversity all year. We played a lot of close games. Thats a great team over there. Im so proud of our guys, that we got it done in crunch time.
Before the drama, the Skippers were on the fast track. In game one, Evan Maloney pitched a gem and Braeden Perry closed it out. Perry picked up where he left off as he took the mound for game two, stretching the scoreless streak to 11 innings.
And the Skippers staked him to a lead. After leaving the bases loaded in the first inning, they took advantage of a chance in the second inning. No. 9 hitter Quincy Rome was hit by a pitch with two outs and moved to second on a wild pitch. T.J. Gormley sent him home with an RBI single. Andrew Ciarniello followed with an RBI double and Josh Lincourt kept the line moving with an RBI single. The Skippers led 3-0 and had chased Hendricken starter Ryan Thompson.
North added two more runs in the fifth. Ciarniello walked and Lincourt singled. Maloney reached on an error that allowed Ciarniello to score. A sacrifice fly by Rob Lamond plated Lincourt and made it 5-0.
Perry had worked out of some trouble in the fourth inning thanks to a pair of strikeouts with runners in scoring position. The Hawks broke through in the fifth. A single, two errors and a sacrifice fly pushed two runs across. Then Durand hit the first of his two home runs, a blast to left field that made it a one-run game.
Perry kept North in front with a scoreless sixth inning, working around a leadoff single and stranding the tying run at third. The Skippers picked up an insurance run in the seventh as Max Proulx lined an RBI double to score Maloney.
With Hendricken down to its last three outs, Perry headed back to the mound, looking to finish off a playoff run in which only he and Maloney had thrown a pitch for the Skippers. That was the way the Skippers would have drawn it up and the senior aces came close to delivering, but reality got messy.
Braeden Campbell led off the seventh with a single. Perry retired the next two batters but still had to get through Durand. The University of Kentucy commit and 2021 Gatorade Player of the Year lined a 1-1 pitch to deep right field. It seemed to still be going up when it crested the fence for a game-tying two-run homer.
The title shot was slipping away in jarring fashion.
That was pretty deflating. It has to be, Maloney said. But we know what were made of. We know were going to fight to the very end. We didnt want to come back tomorrow. We wanted the sweep.
The celebration had barely died down when North began delivering its rebuttal. Evan Beattie relieved Perry and struck out Jared Munoz to end the seventh inning and keep the game tied.
Then the Skippers went to work. Gormley reached on an error with one out in the eighth and Ciarniello stayed hot with an RBI triple to deep right field, which quickly broke the tie. After a walk to Lincourt, Maloney plated Ciarniello for the two-run lead. Lamond then reached on a fielders choice. With a first-and-third situation, the Skippers tried some trickery, with Lamond dancing off first base and getting himself into a rundown. Lincourt broke for home and beat the throw. When the ball got away, Lamond headed for third, and when he saw that nobody was covering home, he never stopped running.
Just like that, the Skippers had a 10-6 lead.
Back and forth, crazy game, Ciarniello said. Were a resilient team. We know we handle adversity better than anybody in the state. Even when they scored those runs, had those big innings, we knew we could come back from that. We knew we still had more left, and we showed it in those last few innings.
One more roadblock emerged in the eighth inning. Beattie stayed on the mound and was greeted by three straight hits, the last of which plated a run that made it 10-7. When Beattie walked Alex Clemmey to load the bases, Kevin Gormley made the call to bring in T.J.
He had been a successful closer in 2021 but a shoulder injury suffered during football season last fall led to surgery and kept him from pitching all spring. He and his father had talked about maybe pitching in an emergency.
And here it was.
I was the safety guy, the last resort, T.J. Gormley said.
The first pitch he threw came right back at him. He snagged the chopper and fired home for an out. Lincourt threw to first for a double play. It was one more perfect answer.
Right before I faced him, I said to Josh, Ground ball back to me, I got you, T.J. said. One hopper right there. A lot of pressure was lifted off.
After a walk loaded the bases again, Gormley got Jack LaRose to hit a fly ball to right-center field. Lamond camped under it and squeezed it for the final out. Durand was left in the on-deck circle.
The Skippers celebrated. They are the first public school to win two straight D-I baseball titles since Cranston West in 2006 and 2007.
We had all the confidence in the world, T.J. Gormley said. This was our goal from day one. We were going to be upset if we didnt repeat.
Perhaps it was always going to end like this not necessarily with another title, but with a championship team going down fighting.
Its been like that all year, Gormley said. Weve won a lot of close games this year. Weve never been tested like that. Its the players. We develop players. We dont inherit talent. We develop talent. And theres a difference when you do that, because they believe in one another. Theyve been playing with one another. Theyre working hard. And it shows: That guys got my back, because I see him putting in the effort. Thats what we do. We just work.
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Championship DNA powered NK baseball to another title - The Independent
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Circulating Tumour DNA Analysis reduced adjuvant chemotherapy use while not compromising recurrence-free survival in stage II colon cancer -…
Posted: at 9:50 pm
1. The circulating tumour DNA-guided approach was non-inferior to the standard clinicopathological approach in terms of 2-year recurrence-free survival.
2. Less adjuvant chemotherapy was used with the circulating tumour DNA approach.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Cancer recurrence risk after surgery is usually estimated clinicopathologically, whereby adjuvant therapy is recommended if reduction of cancer recurrence has been demonstrated. However, in colorectal cancer stage II, classifications of high and low-risk patients are inadequate since many high-risk patients do not have disease recurrence while some low-risk patients do. This study explored the use of circulating tumour DNA (ctDNA) to predict recurrence risk after surgery of stage II colon cancer patients and accordingly better assess their need for adjuvant chemotherapy. Patients were randomly assigned to have their cancer managed according to their ctDNA results or by the standard clinicopathological criteria. Compared to the standard management group, a lower percentage of patients in the ctDNA group received adjuvant chemotherapy. Reassuringly, the 2-year recurrence-free survival in the ctDNA guided management was non-inferior to standard management. Limitations to this study include the lack of randomization of ctDNA-positive and ctDNA-negative patients in receiving treatment or not. A longer follow up is also needed to determine if chemotherapy in ctDNA-positive patients prevents relapse or simply delays it. The strengths of this study are that it has limited bias given the design and that it provides an accurate alternative to the current clinicopathological management. With this ctDNA approach, certain subgroups can avoid unnecessary chemotherapy, along with the physical and financial costs that that accompany it. Overall, ctDNA is a powerful and useful biomarker that will change the current management of stage II colon cancer and future studies will investigate the role of intensification and de-escalation of treatment based on ctDNA.
Click to read the study in NEJM
Click to read an accompanying editorial in the New England Journal of Medicine
Relevant Reading: Adjuvant chemotherapy for stage II colon cancer
In-Depth [randomized control trial]: This phase II multicenter study in Australia randomly assigned 455 patients in a 2:1 ratio to receive ctDNA guided management or standard clinicopathological management of their stage II colon cancer; 302 were in the ctDNA group and 153 in the standard management group. Patients in the ctDNA group who had a positive result receive physicians choice of adjuvant chemotherapy, while the standard treatment proceeded to adjuvant systemic therapy based on standard of care risk stratification criteria. Two-year recurrence-free survival was 93.5% and 92.4% for the ctDNA and standard management groups, respectively (95% confidence interval [CI], -4.1 to 6.2; noninferiority margin, -8.5%). In the ctDNA group, 15% of ctDNA positive patients received adjuvant chemotherapy compared to 28% in the standard management group (relative risk, 1.82%; 95% CI, 1.25 to 2.65). Three-year recurrence-free survival for ctDNA-positive patients who received adjuvant chemotherapy and ctDNA-negative patients who did not was 86.4% and 92.5%, respectively (hazard ratio, 1.83; 95% CI, 0.79 to 4.27). Overall, the ctDNA-guided approach in the treatment of stage II colon cancer reduced adjuvant chemotherapy use while not altering recurrence-free survival.
Image: PD
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