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Miami Herald
03-07-2025
- Health
- Miami Herald
Science seek to tap amazing healing powers of the mouth's interior
ST. PAUL, Minn., July 2 (UPI) -- The cellular action that enables the mouth's interior lining to heal quicky and without scarring has always been a mystery but a new study suggests it may be linked to a specific "signaling pathway." That new knowledge is raising hopes the mouth lining's healing powers could be applied to other skin wounds, which take far longer to heal and often leave permanent, unsightly scars, according to a preclinical study published Wednesday by Cedars-Sinai Medical Center and University of California-San Francisco researchers. The study on mice provides evidence that the "Gas6/AXL" protein/enzyme signaling pathway is likely responsible for the mouth's amazing ability to heal itself completely from even deep bite wounds within a matter of days with no leftover scarring, the authors wrote in the journal Science Translational Medicine. Known as the oral mucosa, the mouth's interior lining heals fast and cleanly, even though it is continuously exposed to different types of microbes, abrasion from foods, motion and tension. This unique regenerative capacity is made possible by specialized gene programs activated during injury, but just how those mechanisms work has been unknown. In the study reported Wednesday, a research team led by Dr. Ophir Klein, executive vice dean of Children's Health at Cedars-Sinai and executive director of Cedars-Sinai Guerin Children's in Los Angeles, found that by manipulating levels of the AXL enzyme they could affect how wounds healed. For instance, if they inhibited AXL in mice, the healing of oral mucosa wounds worsened, making them more like skin wounds. Conversely, when they stimulated AXL in facial skin wounds, they healed more efficiently and with reduced scarring, much like the oral mucosa. Boosting the levels of AXL suppresses the expression of another protein called Focal Adhesion Kinase, or FAK, which plays a significant role in scar formation during wound healing. Should future research validate the benefits for humans, the new knowledge could aid in developing new therapies to heal skin wounds with reduced scarring, Klein said. "We are actively thinking about harnessing AXL-driven repair in both the mouth and the skin, and perhaps in other tissues as well," he told UPI in emailed comments. "One application that comes to mind is to improve healing and reduce scarring in the skin for burn victims or those with other cutaneous disorders. "Another is that there are a number of diseases of the mouth, many of them autoimmune, in which severe oral ulcers form and heal poorly or not at all. These are different from canker sores, also known as aphthous ulcers, which many people get and which typically heal on their own; the more severe ulcers are difficult to treat and cause very significant illnesses, and we currently do not have good therapies for them." A related direction for research could focus on "obtaining a deeper understanding of the effects of AXL signaling on scarring and regeneration at a molecular level, in terms of other components of the signaling pathways," Klein added. "It will also be interesting to explore the role of this pathway in other tissues and organs, and in the context of distinct injuries and perturbations --for example, physical cuts vs heat burns vs irradiation versus chemical insults." Meanwhile, a pair of recent animal studies led by the University of Arizona in Tucson similarly have shown that the use of FAK inhibitors can make skin grafts look more like healthy skin and produce less scarring, raising hopes for a potential new treatment for survivors of blast wounds, burns and other major injuries. Kellen Chen, an assistant research professor in the university's Department of Surgery and lead author of those papers, said the current Cedars-Sinai study appears to add to a mounting list of evidence that "FAK acts as a central mediator of scarring in the oral mucosa gives additional credence to the importance of this factor." Chen was not involved with the new study. "A better understanding of how the oral mucosa heals without scarring through the FAK pathway will allow us to better develop therapies to target FAK for healing in the future," he told UPI. Chen said his team has the funding to pursue Food and Drug Administration approval for a FAK inhibitor, or FAKI, hydrogel therapy and expects to conduct human trials soon. The growing evidence that wound healing can be accelerated at the cellular level "could have strong clinical implications for the treatment of severe injuries for humans and animals, especially because there are zero FDA-approved treatments that reduce scar formation," he added. "Patients with severe injuries or burns can suffer a lifetime of pain and disfigurement from scarring. The potential to heal burn injuries with regeneration, rather than scarring, would dramatically change the lives of these patients." Copyright 2025 UPI News Corporation. All Rights Reserved.
UPI
02-07-2025
- Health
- UPI
Science seek to tap amazing healing powers of the mouth's interior
1 of 2 | The amazing ability of the mouth's lining to quickly heal itself without scarring is likely due to a specific cellular action that could be applied to skin wounds sustained elsewhere on the body, according to a study released Wednesday. File Photo by Molly Riley/UPI | License Photo ST. PAUL, Minn., July 2 (UPI) -- The cellular action that enables the mouth's interior lining to heal quicky and without scarring has always been a mystery but a new study suggests it may be linked to a specific "signaling pathway." That new knowledge is raising hopes the mouth lining's healing powers could be applied to other skin wounds, which take far longer to heal and often leave permanent, unsightly scars, according to a preclinical study published Wednesday by Cedars-Sinai Medical Center and University of California-San Francisco researchers. The study on mice provides evidence that the "Gas6/AXL" protein/enzyme signaling pathway is likely responsible for the mouth's amazing ability to heal itself completely from even deep bite wounds within a matter of days with no leftover scarring, the authors wrote in the journal Science Translational Medicine. Known as the oral mucosa, the mouth's interior lining heals fast and cleanly, even though it is continuously exposed to different types of microbes, abrasion from foods, motion and tension. This unique regenerative capacity is made possible by specialized gene programs activated during injury, but just how those mechanisms work has been unknown. In the study reported Wednesday, a research team led by Dr. Ophir Klein, executive vice dean of Children's Health at Cedars-Sinai and executive director of Cedars-Sinai Guerin Children's in Los Angeles, found that by manipulating levels of the AXL enzyme they could affect how wounds healed. For instance, if they inhibited AXL in mice, the healing of oral mucosa wounds worsened, making them more like skin wounds. Conversely, when they stimulated AXL in facial skin wounds, they healed more efficiently and with reduced scarring, much like the oral mucosa. Boosting the levels of AXL suppresses the expression of another protein called Focal Adhesion Kinase, or FAK, which plays a significant role in scar formation during wound healing. Should future research validate the benefits for humans, the new knowledge could aid in developing new therapies to heal skin wounds with reduced scarring, Klein said. "We are actively thinking about harnessing AXL-driven repair in both the mouth and the skin, and perhaps in other tissues as well," he told UPI in emailed comments. "One application that comes to mind is to improve healing and reduce scarring in the skin for burn victims or those with other cutaneous disorders. "Another is that there are a number of diseases of the mouth, many of them autoimmune, in which severe oral ulcers form and heal poorly or not at all. These are different from canker sores, also known as aphthous ulcers, which many people get and which typically heal on their own; the more severe ulcers are difficult to treat and cause very significant illnesses, and we currently do not have good therapies for them." A related direction for research could focus on "obtaining a deeper understanding of the effects of AXL signaling on scarring and regeneration at a molecular level, in terms of other components of the signaling pathways," Klein added. "It will also be interesting to explore the role of this pathway in other tissues and organs, and in the context of distinct injuries and perturbations --for example, physical cuts vs heat burns vs irradiation versus chemical insults." Meanwhile, a pair of recent animal studies led by the University of Arizona in Tucson similarly have shown that the use of FAK inhibitors can make skin grafts look more like healthy skin and produce less scarring, raising hopes for a potential new treatment for survivors of blast wounds, burns and other major injuries. Kellen Chen, an assistant research professor in the university's Department of Surgery and lead author of those papers, said the current Cedars-Sinai study appears to add to a mounting list of evidence that "FAK acts as a central mediator of scarring in the oral mucosa gives additional credence to the importance of this factor." Chen was not involved with the new study. "A better understanding of how the oral mucosa heals without scarring through the FAK pathway will allow us to better develop therapies to target FAK for healing in the future," he told UPI. Chen said his team has the funding to pursue Food and Drug Administration approval for a FAK inhibitor, or FAKI, hydrogel therapy and expects to conduct human trials soon. The growing evidence that wound healing can be accelerated at the cellular level "could have strong clinical implications for the treatment of severe injuries for humans and animals, especially because there are zero FDA-approved treatments that reduce scar formation," he added. "Patients with severe injuries or burns can suffer a lifetime of pain and disfigurement from scarring. The potential to heal burn injuries with regeneration, rather than scarring, would dramatically change the lives of these patients."
Miami Herald
21-05-2025
- Health
- Miami Herald
Lung cancer risk in never-smokers predicted by AI tool ‘Sybil'
ST. PAUL, Minn., May 19 (UPI) -- With lung cancer rates among non-smokers rising, especially young East Asian women, a new study released Monday is touting the promise of an artificial intelligence tool to "strongly" predict who's most at risk. Lung cancer has long been associated with smoking. But even as overall rates steadily drop and smoking decreases around the world, a unique population of young East Asians are seeing a 2% annual increase in lung cancer cases -- even though half of them have never smoked. The cause of this remains unknown, but suspicion is centered on genetic mutations developed during a person's lifetime rather than inherited, such as damage to a gene that codes for a protein known as EGFR, which prevents cells from growing too quickly. This genetic damage is believed to be caused by environmental toxins including second-hand smoke and even fumes produced by high-temperature stir-fry cooking in rooms that lack proper ventilation. Globally, more than 50% of women diagnosed with lung cancer are non-smokers, compared to 15% to 20% of men. Meanwhile, an estimated 57% of Asian-American women diagnosed with lung cancer have never smoked, compared to only about 15% of all other women, according to a recent University of California-San Francisco study. Against this backdrop of rising cancer cases among seemingly low-risk women, the potential of AI to accurately predict who may be most suspectable to a surprise lung cancer diagnosis has generated considerable interest around the world. In a paper presented Monday at the American Thoracic Society's medical conference in San Francisco, Dr. Yeon Wook Kim of the Seoul National University Bundang Hospital reported a new AI tool dubbed "Sybil" has proven to be accurate in identifying which "true low-risk individuals" are more likely to develop lung cancer -- all foretold from a single low-dose chest CT scan, or LDCT. Sybil, named after the female seers of ancient Greek mythology, was developed in 2023 by researchers at the Massachusetts Institute of Technology's Abdul Latif Jameel Clinic for Machine Learning in Health, the Mass General Cancer Center and Chang Gung Memorial Hospital in Taiwan. It was trained first by feeding it LDCT images largely absent of any signs of cancer, since early-stage lung cancer occupies only tiny portions of the lung and is invisible to the human eye. Then, researchers gave Sybil hundreds of scans with visible cancerous tumors. In its first run, Sybil was able to deliver "C-indices" of up to 0.81 in predicted future occurrences of lung cancer from analyzing one LDCT. Models achieving predictive C-index scores of over 0.7 are considered "good" and those over 0.8 are "strong." This week's Korean study validated those results. Kim and his colleagues evaluated 21,087 people ages 50 to 80 who underwent self-initiated LDCT screening between January 2009 and December 2021 in a tertiary hospital-affiliated screening center in South Korea. These subjects were followed up until June 2024. Baseline LDCTs were analyzed with Sybil to calculate the risk of lung cancer diagnosis within one to six years. Analyses were performed for individuals with various smoking histories, ranging from more than 20 "pack-years" to never-smokers, who comprised 11,098 of the participants. Among all participants, 257 (including 115 never-smokers) were diagnosed with lung cancer within six years from the baseline LDCT. Sybil achieved a C-index for lung cancer prediction at one year of 0.86 and 6 years of 0.74 for all the participants, while among never-smokers, one-year and six-year C-indices were 0.86 and 0.79, respectively. Kim told UPI the results hold the promise of helping to regularize lung cancer screening in Asia, where those efforts are inconsistent and, due to differing demographics, sometimes are at a "disconnect" with international screening criteria. "Asia bears the highest burden of lung cancer, accounting for over 60% of new cases and related deaths worldwide," he said in emailed comments. "A growing proportion of this burden is observed among individuals who have never smoked, particularly among women. "In Korea, more than 85% of female lung cancer patients are non-smokers. As a result, increasing attention has been given to evaluating the effectiveness of lung cancer screening, or LCS, in traditionally low-risk populations in Asia." Government-led programs and initiatives have expanded to include never-smokers into their LCS efforts, while other efforts varying from international guidelines due to their inclusion of such never-smokers have "gained traction in East Asian countries, including South Korea, Taiwan and China," Kim said. AI tools like Sybil could be used to develop "personalized strategies" for patients who have already undergone LDCT screening, but have not yet had follow-ups, he added, while cautioning that further validation will be needed "to confirm the model's potential for clinical use. "While the need for screening low-risk groups may be justified in certain settings, the lack of evidence from randomized trials limits the development of long-term LCS strategies for these populations." Researchers, meanwhile, are "actively" working on expanding Sybil's uses into other personalized health applications, said Adam Yala, an assistant professor at the UCSF/UC-Berkeley Joint Program in Computational Precision Health and one of the AI model's developers. "One, this is broadly applicable across many different types of cancers," he told UPI. "We've got processes ongoing for breast cancer, and we're also working on prostate and pancreas cancers. "And there's also evidence that from CT scans you could predict sudden deaths from cardiovascular disease. This would provide early detection, giving you a better opportunity for early intervention to provide better outcomes. So it's not uniquely about cancer. ... There's a version of this for cardiovascular health, and there could be other areas of medicine, as well." AI's potential to provide health benefits, Yala added, "is totally untapped. For instance, now we're only looking at a patient's CT scan once, but over time, you could look at multiple CTs. Mammograms, as well. There's a lot of data available there. It's a field at its infancy." Copyright 2025 UPI News Corporation. All Rights Reserved.
Yahoo
19-05-2025
- Health
- Yahoo
Lung cancer risk in never-smokers predicted by AI tool 'Sybil'
ST. PAUL, Minn., May 19 (UPI) -- With lung cancer rates among non-smokers rising, especially young East Asian women, a new study released Monday is touting the promise of an artificial intelligence tool to "strongly" predict who's most at risk. Lung cancer has long been associated with smoking. But even as overall rates steadily drop and smoking decreases around the world, a unique population of young East Asians are seeing a 2% annual increase in lung cancer cases -- even though half of them have never smoked. The cause of this remains unknown, but suspicion is centered on genetic mutations developed during a person's lifetime rather than inherited, such as damage to a gene that codes for a protein known as EGFR, which prevents cells from growing too quickly. This genetic damage is believed to be caused by environmental toxins including second-hand smoke and even fumes produced by high-temperature stir-fry cooking in rooms that lack proper ventilation. Globally, more than 50% of women diagnosed with lung cancer are non-smokers, compared to 15% to 20% of men. Meanwhile, an estimated 57% of Asian-American women diagnosed with lung cancer have never smoked, compared to only about 15% of all other women, according to a recent University of California-San Francisco study. Against this backdrop of rising cancer cases among seemingly low-risk women, the potential of AI to accurately predict who may be most suspectable to a surprise lung cancer diagnosis has generated considerable interest around the world. In a paper presented Monday at the American Thoracic Society's medical conference in San Francisco, Dr. Yeon Wook Kim of the Seoul National University Bundang Hospital reported a new AI tool dubbed "Sybil" has proven to be accurate in identifying which "true low-risk individuals" are more likely to develop lung cancer -- all foretold from a single low-dose chest CT scan, or LDCT. Sybil, named after the female seers of ancient Greek mythology, was developed in 2023 by researchers at the Massachusetts Institute of Technology's Abdul Latif Jameel Clinic for Machine Learning in Health, the Mass General Cancer Center and Chang Gung Memorial Hospital in Taiwan. It was trained first by feeding it LDCT images largely absent of any signs of cancer, since early-stage lung cancer occupies only tiny portions of the lung and is invisible to the human eye. Then, researchers gave Sybil hundreds of scans with visible cancerous tumors. In its first run, Sybil was able to deliver "C-indices" of up to 0.81 in predicted future occurrences of lung cancer from analyzing one LDCT. Models achieving predictive C-index scores of over 0.7 are considered "good" and those over 0.8 are "strong." This week's Korean study validated those results. Kim and his colleagues evaluated 21,087 people ages 50 to 80 who underwent self-initiated LDCT screening between January 2009 and December 2021 in a tertiary hospital-affiliated screening center in South Korea. These subjects were followed up until June 2024. Baseline LDCTs were analyzed with Sybil to calculate the risk of lung cancer diagnosis within one to six years. Analyses were performed for individuals with various smoking histories, ranging from more than 20 "pack-years" to never-smokers, who comprised 11,098 of the participants. Among all participants, 257 (including 115 never-smokers) were diagnosed with lung cancer within six years from the baseline LDCT. Sybil achieved a C-index for lung cancer prediction at one year of 0.86 and 6 years of 0.74 for all the participants, while among never-smokers, one-year and six-year C-indices were 0.86 and 0.79, respectively. Kim told UPI the results hold the promise of helping to regularize lung cancer screening in Asia, where those efforts are inconsistent and, due to differing demographics, sometimes are at a "disconnect" with international screening criteria. "Asia bears the highest burden of lung cancer, accounting for over 60% of new cases and related deaths worldwide," he said in emailed comments. "A growing proportion of this burden is observed among individuals who have never smoked, particularly among women. "In Korea, more than 85% of female lung cancer patients are non-smokers. As a result, increasing attention has been given to evaluating the effectiveness of lung cancer screening, or LCS, in traditionally low-risk populations in Asia." Government-led programs and initiatives have expanded to include never-smokers into their LCS efforts, while other efforts varying from international guidelines due to their inclusion of such never-smokers have "gained traction in East Asian countries, including South Korea, Taiwan and China," Kim said. AI tools like Sybil could be used to develop "personalized strategies" for patients who have already undergone LDCT screening, but have not yet had follow-ups, he added, while cautioning that further validation will be needed "to confirm the model's potential for clinical use. "While the need for screening low-risk groups may be justified in certain settings, the lack of evidence from randomized trials limits the development of long-term LCS strategies for these populations." Researchers, meanwhile, are "actively" working on expanding Sybil's uses into other personalized health applications, said Adam Yala, an assistant professor at the UCSF/UC-Berkeley Joint Program in Computational Precision Health and one of the AI model's developers. "One, this is broadly applicable across many different types of cancers," he told UPI. "We've got processes ongoing for breast cancer, and we're also working on prostate and pancreas cancers. "And there's also evidence that from CT scans you could predict sudden deaths from cardiovascular disease. This would provide early detection, giving you a better opportunity for early intervention to provide better outcomes. So it's not uniquely about cancer. ... There's a version of this for cardiovascular health, and there could be other areas of medicine, as well." AI's potential to provide health benefits, Yala added, "is totally untapped. For instance, now we're only looking at a patient's CT scan once, but over time, you could look at multiple CTs. Mammograms, as well. There's a lot of data available there. It's a field at its infancy."
The Independent
23-04-2025
- Politics
- The Independent
Trump has signed 124 orders in less than 100 days. Scholars warn this is a constitutional crisis
As Donald Trump nears the end of his first 100 days in office, he has issued a record-breaking high of 124 executive orders, while signing a record-breaking low of just five new bills into law, and caused concerns among constitutional scholars. 'These orders are extraordinary, not just in their number, but in their breadth,' said Rory Little, a law professor at the University of California- San Francisco said at a recent panel discussion. 'The current state of affairs can be characterized I think with no exaggeration as a crisis, a challenge to the rule of the law in the United States.' Others in the panel noted how many of Trump's executive orders have pushed into areas typically run by states. Trump has set records for both his executive order tally and how few bills he has received from Congress. Instead, he has governed by his signature and targeted immigration, tariffs, diversity programs, education and a host of other areas. He has taken pen to paper to reshape America in his image with little resistance or pushback. 'While some may legitimately applaud the policy goals that underlie some of these actions, I hope we can all agree these policy goals should be pursued lawfully, lest we end up living in the type of system envisioned by the president, where he is the only law,' fellow professor Jodi Short said. Having signed only five bills means that Trump has signed fewer into law at this point in his presidency than any new president in the last 70 years, according to government records. He is followed by Joe Biden and George W Bush, who had each signed only seven apiece at the same juncture. According to the records, at the same point in his first presidency, Trump had signed 24 bills into law. Prior to that, in 2009, Barack Obama had signed 11 bills into law at the 100-day mark, and during his presidency, in 1993, Bill Clinton had signed 21 bills. Trump's bills so far have included three Congressional Review Act resolutions overturning Biden administration regulations, the Laken Riley Act and a stopgap funding bill needed to avoid a government shutdown. A bill is a legislative proposal that becomes a law after it is passed and signed by the president. In contrast, within his first three months back in the White House, Trump has already signed 124 executive orders, closing in on the totals issued by some of his predecessors during their entire terms. In total, Biden signed 162 executive orders, Obama signed 277, Bush signed 291, and Clinton signed 364, according to the Federal Register. Trump, in his first term signed 220. An executive order is a written directive, signed by the president, that orders the government to take specific actions to ensure 'the laws be faithfully executed,' according to the ACLU. Such orders do not need the approval of Congress, but are open to legal challenge. Executive orders mean that, as president, Trump can essentially tell federal agencies how to interpret, implement or enforce a law – as long as it is within their constitutional authority, and do not violate any federal laws. Trump's 124 executive orders have already prompted dozens of federal lawsuits, challenging the constitutionality of the orders and the extent to which they are being used. 'Executive orders can be an effective way to carry out policy while staying within the rule of law,' an ACLU briefing stated. 'However, as we've seen with the Trump administration, they can also cause chaos, damage the democratic process and harm our must vulnerable communities.' Tennessee Rep. Steve Cohen called out the administration for acting 'illegally and unconstitutionally in ways that weaken our democratic institutions.' Others have claimed that the actions risk prompting a 'constitutional crisis.' On his first day in office, Trump signed an executive order to end birthright citizenship for children born in the U.S. to parents who are not in the country lawfully. It was challenged by multiple immigrants' rights advocates, an expectant mother and several states, resulting it being blocked temporarily by several federal judges. Two days later, on January 22, Trump signed an executive order ending diversity, equity and inclusion programs at government agencies, and later another aimed at similar programs in the military. Following a challenge by the National Association of Diversity Officers in Higher Education, a federal judge temporarily blocked the administration from terminating or changing federal contracts, considered to be equity-related. Despite its battles in the courts, the Trump administration has doubled down on the authority of the president and his orders. White House press secretary Karoline Leavitt previously claimed the judicial branch was behaving 'erroneously,' after several judges blocked various orders "I would like to point out that the judges in this country are acting erroneously," Leavitt said in a Wednesday news briefing. "We have judges who are acting as partisan activists from the bench." Leavitt previously insisted that 'the real constitutional crisis is taking place within our judicial branch.' Yet Trump's critics continue to argue that the intense volume of his executive orders amounts to, at the very least, an 'overreach,' and, at worst, an unconstitutional abuse of power. 'Congress is supposed to have the purse,' Douglas Brinkley, professor of history at Rice University, told PBS News in 2019. 'It's supposed to run the money. Donald Trump now is doing something unprecedented by grabbing the funding from Congress and reallocating it in his own — with his own whims.' As recently as Tuesday, a federal judge blocked the Trump administration from enforcing an executive order targeting the law firm Susman Godfrey, describing it as an unconstitutional 'personal vendetta.' 'Frankly, I think the Framers of our Constitution would see this as a shocking abuse of power,' U.S. District Judge Loren AliKhan said.
