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Genetics and other factors that can determine if a woman is at risk for a recurrence of breast cancer have been identified by investigators at Georgetown Lombardi Comprehensive Cancer Center, providing new research avenues for preventing a new tumor from developing. The discovery was made possible by an advanced technology developed at Georgetown Lombardi that allows laboratory researchers to greatly expand, or multiply, hard-to-extract breast tissue cells.
The finding appeared April 22, 2022, in Scientific Reports.
The researchers focused on breast epithelial cells, which are the layer of cells that form the ducts and lobes which make milk during lactation. The investigators extracted these cells from donated non-cancerous tissue in the same breast as the one that had cancerous tissue removed during a mastectomy. The scientists were looking for numerous factors that could kick-start recurrence, but their main target was the entire collection of RNA sequences in a cell — the transcriptome — that helps determine when and where each gene is turned on or off in a cell.
Even though surgical techniques continue to improve, undetectable microscopic pieces of tumor can remain and are one factor for recurrence of breast cancer in up to 15 percent of women, sometimes years after surgery; people with hormone-receptor positive breast cancer have the highest risk of recurrence.
When analyzing expanded epithelial cells from women who had chemotherapy before their surgery, the researchers found significantly altered RNA. In particular, they saw significant changes in genes that had previously been recognized as prognostic indicators for cancer.
“When a person is diagnosed with breast cancer, we have several tools, including testing for genes such as BRCA1/2, to decide whether they should get certain kinds of chemotherapy or just receive hormonal therapy. But the tools we have are not as precise as we would like,” says Priscilla Furth, M.D., professor of oncology and medicine at Georgetown Lombardi and corresponding author of the study. “About one in eight women are diagnosed with breast cancer in the developed world. We hope that our findings will help lead to more precise and directed screening in the future, sparing women unneeded procedures as we currently screen almost all women between the ages of 40 to 70, sometimes very aggressively.”
The researchers also noted that there are implications for women who have not had breast cancer as some of the RNA alterations were linked to mammary stem cell formation. Stem cells are self-renewing and related to growth and development. Mammary stem cells are adult stem cells that can differentiate, or change function, into specialized mammary epithelial cells. If these cells get dysregulated, there is an increased potential for cancer. Cells from pregnant women were of particular interest to the researchers as pregnancy usually triggers extra renewing cycles in a cell, potentially increasing the risk of cancer.
This research effort was greatly aided by the conditionally reprogrammed cells (CRC) technique that was invented and patented at Georgetown. This study used CRC for the initial isolation of epithelial cells. CRC is the only known system that can indefinitely grow healthy as well as cancer cells; up to a million new cells can be grown in a week. Heretofore, one of the key problems in studying these cells was that epithelial cell cultures were often contaminated with the other cell types, particularly fibroblasts which grow very quickly in culture while epithelial cells grow a bit slower. Primary tumor cells also can be difficult to isolate but the researchers had increased success using the CRC technique compared to conventional methods.
“Many of our cancer survivors say to me, ‘please do work that will benefit my daughter.’ My response is that’s why I’m in the field of cancer prevention,” says Furth. “Anything we can do to prevent the occurrence or recurrence of cancer is a significant step forward and we think this finding may be an important contribution to reducing misdiagnosis as well as point to ways to develop better therapies to treat the disease.”
In addition to Furth, the other authors from Georgetown include Sahar J. Alothman, Keunsoo Kang, Xuefeng Liu, Ewa Krawczyk, Redha I. Azhar, Rong Hu, David Goerlitz and Bhaskar V. Kallakury,
Funding includes grants from NCI (RO1CA112176 and P30CA051008) and the King Abdullah Scholarship Program, Kingdom of Saudi Arabia.

In a small but multi-institutional study, an artificial intelligence-based system improved providers’ assessments of whether patients with bladder cancer had complete response to chemotherapy before a radical cystectomy (bladder removal surgery).
Yet the researchers caution that AI isn’t a replacement for human expertise and that their tool shouldn’t be used as such.
“If you use the tool smartly, it can help you,” said Lubomir Hadjiyski, Ph.D., a professor of radiology at the University of Michigan Medical School and the senior author of the study.
When patients develop bladder cancer, surgeons often remove the entire bladder in an effort to keep the cancer from returning or spreading to other organs or areas. More evidence is building, though, that surgery may not be necessary if a patient has zero evidence of disease after chemotherapy.
However, it’s difficult to determine whether the lesion left after treatment is simply tissue that’s become necrotic or scarred as a result of treatment or whether cancer remains. The researchers wondered if AI could help.
“The big question was when you have such an artificial device next to you, how is it going to affect the physician?” Hadjiyski said. “Is it going to help? Is it going to confuse them? Is it going to raise their performance or will they simply ignore it?”
Fourteen physicians from different specialties — including radiology, urology and oncology — as well as two fellows and a medical student looked at pre- and post-treatment scans of 157 bladder tumors. The providers gave ratings for three measures that assessed the level of response to chemotherapy as well as a recommendation for the next treatment to be done for each patient (radiation or surgery).

WASHINGTON — Does the Biden administration really want and intend to fight for a higher court reversal of the ruling this week striking down its mask mandate on airplanes, trains and other public transportation — as its high-profile appeal of the case seemed to suggest?Legal specialists raised another possibility on Thursday: The administration may instead be buying time and thinking about trying to erase the ruling — a move that would allow it to protect the powers of the Centers for Disease Control and Prevention to respond to a future crisis — but without reviving a mask mandate.The tell, several outside specialists said, was that the Biden administration was letting days pass without seeking a stay of the ruling, the step that could most immediately resurrect the mask requirement.“Basically, it is giving up on the mask mandate,” said Lawrence O. Gostin, a Georgetown University professor of global health law who advised the White House on the case. “The administration’s goal is a legal principle, which is to ensure that the C.D.C. has strong public health powers to fight Covid and to fight future pandemics. And it appears much less important to them to quickly reinstate the mask mandate.”In fact, the administration has shifted away from masks as critical to the pandemic fight for two months. President Biden and other top officials have increasingly presented masks as a matter of personal choice, not federal policy.The requirement to mask on public transportation, put in place soon after Mr. Biden took office in January, has been the exception. It was set to expire May 3, but with rising infections nationwide, the C.D.C. had left open the possibility of extending it again before the federal judge, Kathryn Kimball Mizelle of the Middle District of Florida, struck it down on Monday.Amid fluid deliberations about what to do, Karine Jean-Pierre, the principal deputy White House press secretary, told reporters that the administration was appealing because “the C.D.C. must have the essential public health authority” to make critical decisions now and during future health crises.“That is what is at stake right now,” she said.Because the case turns in part on whether the C.D.C. was justified in enacting the mandate as an emergency measure that offered no room for public notice or comment, it is notable that the administration appealed the ruling while not seeking an immediate stay. The failure to try to keep the mask order in place could undercut the government’s argument that there was an urgent need for the requirement; otherwise it would have tried to keep it in place, legal specialists say.If the government really wanted to fight its appeal all the way to a decision on whether to overturn Judge Mizelle, said Stephen I. Vladeck, a University of Texas at Austin law professor who specializes in federal courts, “then they totally botched this, because it’s Thursday and the ruling was on Monday and they haven’t done anything about it yet.”But Mr. Vladeck contended that the failure to seek a stay may make sense if the Biden legal team was instead trying to protect the C.D.C.’s power with no real intention of trying to get a higher court to reinstate the mask mandate.He pointed to an obscure legal doctrine under which if a case is on appeal when the dispute becomes moot for reasons unrelated to the litigation, an appeals court can remand it to the district court with instructions not only to dismiss the case but to vacate the district court’s ruling — meaning wipe it from the books.The government, he said, may be giving itself that option after the mandate’s planned expiration on May 3.A mixed of the masked and maskless at Hartsfield-Jackson International Airport in Atlanta after the mandate was overturned.Dustin Chambers for The New York TimesIn her ruling, Judge Mizelle put forward a cramped interpretation of the agency’s regulatory powers to protect against the interstate spread of infectious diseases. Both she and a majority of the appeals court that oversees her court were appointed by President Donald J. Trump, whose legal advisers openly promoted their search for potential judges who would be skeptical of the power of regulatory agencies.Asked by a reporter on Thursday why the Justice Department had not sought an immediate stay, Attorney General Merrick B. Garland called that “a tactical strategy question.” Giving no further explanation, he said the matter would be resolved by litigators in the Justice Department.But, he added, “our reason for appealing is we believe that the C.D.C. has clear statutory authority for the mask mandate, and the C.D.C. has assessed that it is necessary for the health of the American people — particularly the traveling public.”Michele Goodwin, a law professor who specializes in health policy at the University of California, Irvine, said the standards for winning a request to stay a judicial order can be even higher than for an appeal. Fighting for one and losing it, she said, would raise particular risks of an appeals court decision that could take a similarly narrow view of what the C.D.C. may do in a public health crisis — and that, unlike a district court ruling, would also be a binding precedent.“Losing sends a very strong message, and not just for the matter that happens to be at hand, but for other cases related to public health and safety,” she said.The C.D.C. said on Wednesday that masking remained necessary to protect the public health of passengers on planes, trains, buses and subways, and a recent poll showed that 56 percent of Americans support the requirement. But airlines have called for an end to the requirement for months. And aside from public transportation, the administration has been deliberately moving away from masking as an essential pandemic tool for weeks.Asked on April 11 why Mr. Biden wore a mask the previous weekend while Vice President Kamala Harris had stood over him maskless at an event, Jen Psaki, the White House press secretary, said it was up to each person to decide what to do.“We all make decisions. Some people in here are wearing masks to make them more comfortable, or because they chose to that day,” she said, perhaps because they will be around family members or others who are particularly vulnerable. “And the president makes that decision, as we all do as well.”In late February, the C.D.C. changed its guidelines in a way that made it far less likely that a county would be considered high risk, and specified that it recommended indoor mask-wearing in high-risk areas. In areas of moderate risk — like Manhattan and Washington, D.C. — those who are particularly vulnerable to severe illness from the virus should talk to their health care providers about whether to wear a mask, the revised rules say.“Our emphasis right now is on getting people information and tools they need to make decisions for themselves,” Dr. Greta Massetti, a senior epidemiologist who is helping lead the agency’s pandemic response, said in an interview last week. Those choices should be “based on their own personal level of risk and their risk tolerance,” she said.Sheryl Gay Stolberg

SharecloseShare pageCopy linkAbout sharingAuthorities in Shanghai have said they will tighten the enforcement of lockdown measures, as a Covid surge continues in China’s financial capital.New measures include placing electronic door alarms to prevent those infected from leaving, as well as evacuating people to disinfect their homes. Earlier this week, hundreds were forcibly evacuated from their homes to allow for buildings to be disinfected.The restrictions will take Shanghai’s lockdown into its fifth week. Shanghai city officials said all infected patients and close contacts will be transferred to government-run centralised quarantine. In addition, disinfection measures will be escalated in some of the city’s worst-hit areas. This will likely mean some residents will be forced to move out temporarily – including those who have tested negative.The move comes days after people in two other Shanghai communities – Beicai and Pingwang – were ordered to leave their residences for temporary accommodations. In Beicai, an official notice issued to residents told them to pack their belongings and leave their wardrobe doors open.They were also told to leave open the front door of their home and their pets behind. Images on social media of people queuing with packed suitcases at night-time showed the scale of the operation.As the vast lockdown approaches its fifth week authorities show no sign of easing up in their determination to maintain China’s now battered “zero Covid” strategy. In fact they’re escalating. In the worst hit areas, people’s homes will be disinfected. This will likely mean some residents are forced to move out temporarily, even those who’ve tested negative. We can make this assertion because earlier this week the BBC reported on the mass evacuation and forced removal of hundreds of people from their homes in at least two areas of the city, to allow for mass cleansing. Shanghai city officials also re-iterated something that remains crucial – that all infected patients and close contacts should be transferred to government-run centralised quarantine centres. They want people discharged sooner, once they are negative. But as the Party mouthpiece People’s Daily newspaper said on its front page last week, “persistence is victory”. The latest measures signals the lengths to which Chinese authorities are willing to go to stop the spread of Covid in Shanghai – regarded as the country’s financial and business hub. Whole communities forced to move in Shanghai’s war on CovidWhy Shanghai has changed its approach to CovidShanghai lockdown residents ‘running out of food’Some in locked-down areas of the city have been struggling to access food supplies, and forced to wait for government drop-offs of vegetables, meat and eggs.The lockdown extension has overwhelmed delivery services, grocery shop websites and even the distribution of government supplies.Officials are still trying to maintain the country’s zero-Covid strategy which prioritises eliminating the virus over living with it as many countries have now chosen to do. But the increased transmissibility and milder nature of the Omicron variant has led to questions over whether the current strategy is sustainable in the long run.The latest outbreak in Shanghai, first detected in late March, has seen more than 400,000 cases recorded so far and 36 deaths. Nearly all were elderly, unvaccinated residents with underlying health problems, according to Chinese officials. As a result, the city’s 25 million people have been ordered to stay home.This video can not be playedTo play this video you need to enable JavaScript in your browser.More on this storyWhy Shanghai has changed its approach to CovidOmicron vs Zero-Covid: How long can China hold on?The economic cost of China’s zero-Covid policy

SharecloseShare pageCopy linkAbout sharingImage source, PA MediaUK doctors believe they have documented the longest Covid infection on record – a patient they treated who had detectable levels of the virus for more than 16 months, or 505 days, in total.The unnamed individual had other underlying medical conditions and sadly died in hospital in 2021. Persistent infections such as this are still rare, say the London medics. Most people naturally clear the virus, but the patient in question had a severely weakened immune system. Chronic infections like these need studying to improve our understanding of Covid and the risks it can pose, say experts.The patient first caught Covid in early 2020. They had symptoms and the infection was confirmed with a PCR test. They were in and out of hospital many times over the next 72 weeks, for both routine checks and care. On each occasion – about 50 in all – they tested positive, meaning they still had Covid. The doctors, from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, say detailed lab analysis revealed it was the same, persistent infection, rather than repeated bouts. The patient could not shake the infection, even after being given antiviral drugs. This is different to “long Covid”, where the virus is cleared from the body but symptoms persist.One of the medics who will be presenting the findings at a medical conference – the European Congress of Clinical Microbiology and Infectious Diseases – is Dr Luke Blagdon Snell. He told the BBC: “These were throat swab tests that were positive each time. The patient never had a negative test. And we can tell it was one continuous infection because the genetic signature of it – the information we got from sequencing the viral genome – was unique and constant in that patient.”The man who tested positive for Covid 43 timesWoman caught Covid twice within record 20 daysProlonged infections are rare but important, say the researchers, because they might give rise to new variants of Covid – although that did not happen in this case.Dr Snell said: “The virus is still adapting to the human host when people are infected for a long time. It might provide an opportunity for Covid to accrue new mutations. “Some of these patients that we have studied have mutations that have been seen in some of the variants of concern.”He stressed that none of the nine patients they checked had spawned a new dangerous variant. Someone with a chronic infection might not be contagious to others, he added.More on this storyThe man who tested positive for Covid 43 times’I’ve had long Covid for two years now’Woman caught Covid twice within record 20 daysRelated Internet LinksECCMID 2022The BBC is not responsible for the content of external sites.

A recent study by the Faculty of Sport and Health Sciences at the University of Jyväskylä and the Gerontology Research Center (Finland) investigated the paths from childhood socioemotional behaviour to midlife health behaviour decades later. Socioemotional behaviour at age 8 predicted health behaviour both directly and indirectly through education.
There are a wide variety of factors behind health behaviour and one of them is personality. Differences in behaviour and response style between individuals are already visible in young children. A recent paper examined the role of socioemotional behaviour in children in relation to physical activity, smoking, alcohol consumption and body mass index assessed up to 42 years later.
Well-controlled behaviour in girls, indicating a tendency to behave kindly and constructively in conflicting situations, predicted more physical activity in middle age. Social activity, which was seen, for example, as an eagerness to talk and play with other children, predicted heavier alcohol consumption in girls and smoking in boys. 
“Well-controlled behaviour may appear as good self-discipline and the ability to follow the exercise plans in adulthood,” says postdoctoral researcher Tiia Kekäläinen. “Social activity, on the other hand, may have led later to social situations where smoking and alcohol consumption were started.”
The educational path matters
Some paths between childhood socioemotional behaviour and midlife health behaviours went through education. Social activity in girls and well-controlled behaviour in both girls and boys predicted better school success in adolescence and higher education in adulthood. High educational achievement was linked, in turn, to less smoking and alcohol use.
“The results are in line with previous results based on this same longitudinal data and other studies,” says Kekäläinen. “In particular, well-controlled behaviour has been found to contribute to school success and education. These may provide information and skills that help to make healthy choices. The results of this paper suggest that differences in individuals’ behaviour already visible in childhood are reflected in adulthood both directly and through various mediating mechanisms.”
The study was part of the Jyväskylä Longitudinal Study of Personality and Social Development (JYLS) in which the same individuals have been followed since 1968 when they were 8 years old. This study used data on socio-emotional behaviour and parental socioeconomic status at age 8, school success at age 14, educational background at age 27, personality traits at age 33, and health behaviours at age 36, 42, and 50. The data collection in JYLS at various stages has been funded by the Academy of Finland (latest funding number 323541) and the writing of this publication was funded by the Ministry of Education and Culture (PATHWAY-project).
Story Source:
Materials provided by University of Jyväskylä – Jyväskylän yliopisto. Note: Content may be edited for style and length.

A new study has prompted scientists to reconsider a once-popular yet controversial idea in stroke research.
Neuroscientists believed that, in the aftermath of a stroke, calming overexcited neurons might prevent them from releasing a toxic molecule that can kill neurons already damaged by lack of oxygen. This idea was supported by studies in cells and animals, but it lost favor in the early 2000s after numerous clinical trials failed to improve outcomes for stroke patients.
But a fresh approach has yielded evidence that the idea may have been discarded too hastily. The new findings are available online in the journal Brain.
By scanning the whole genomes of nearly 6,000 people who had experienced strokes, researchers at Washington University School of Medicine in St. Louis identified two genes associated with recovery within the pivotal first 24 hours after stroke. Events — good or bad — that occur in the first day set stroke patients on their courses toward long-term recovery. Both genes turned out to be involved in regulating neuronal excitability, providing evidence that overstimulated neurons influence stroke outcomes.
“There’s been this lingering question about whether excitotoxicity really matters for stroke recovery in people,” said co-senior author Jin-Moo Lee, MD, PhD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “We can cure stroke in a mouse using blockers of excitotoxicity. But in humans we performed numerous clinical trials, and we couldn’t move the needle. Every last one of them was negative. In this study, out of 20,000 genes, the top two genetic hits point to mechanisms involving neuronal excitation. That’s pretty remarkable. This is the first genetic evidence that shows excitotoxicity matters in people and not just in mice.”
Every year nearly 800,000 people in the U.S. have ischemic strokes, the most common kind of stroke. Ischemic strokes occur when a clot blocks a blood vessel and cuts off oxygen to part of the brain, triggering sudden numbness, weakness, confusion, difficulty speaking or other symptoms. Over the next 24 hours, some people’s symptoms continue to worsen while others’ stabilize or improve.

The virus that causes COVID-19, SARS-CoV-2, can directly infect a specialized type of kidney cell. The discovery helps explain why acute kidney injury is one of the main complications observed in patients with severe COVID-19, according to biomedical engineers and virologists at Duke University.
The research appeared online April 20 in the journal Frontiers in Cell and Developmental Biology.
When COVID-19 began spreading across the globe in early 2020, physicians knew that the virus primarily infected cells in the respiratory tract. But as the case numbers began to grow, physicians were surprised to see that many patients — especially those with severe COVID-19 — were also developing injuries to their kidneys.
The issue came to Samira Musah’s attention when she attended a virtual symposium in the spring of 2020. Musah, an assistant professor of biomedical engineering and medicine at Duke, listened as physicians presented research that described how patients who had never experienced any kidney-related issues were developing kidney disease after getting sick with COVID-19.
“It was shocking to hear doctors describe how patients who were healthy suddenly developed kidney injury and needed to go on dialysis after contracting SARS-CoV-2,” said Musah. “It was clear that the virus was doing something to the kidneys, but it was so early in the pandemic that nobody was sure what was going on.”
In previous work, Musah and her team showed that they could guide human induced pluripotent stem cells to develop and mature into functional podocytes, which is a specific type of kidney cell that helps control the removal of toxins and waste from the blood. Musah and Titilola Kalejaiye, a postdoctoral fellow in the lab, wanted to see if they could use this model to determine how and why SARS-CoV-2 was capable of damaging kidney cells.

Gun violence in the United States has increased to the point that it now kills more children than any other cause, including car accidents, and pediatricians may not be entirely prepared.
While health care providers are taught to recognize and treat many public health crises, including the opioid crisis, the COVID-19 pandemic, and the obesity crisis, violence related to firearms has not always been seen through that lens.
In an analysis of the most recent data available through the CDC, clinical researchers from the Medical University of South Carolina revealed that firearm injuries are now the leading cause of death among children under 19, and the racial gap between black and white youth is widening. The article, recently published in the journal Pediatrics, calls for physicians and other health care workers to recognize this as an epidemiological and public health challenge and to help find solutions.
Annie Andrews, M.D., a pediatrician and assistant professor of pediatrics at MUSC, led the charge to describe the most up-to-date statistics on firearm-related injuries and death to set the stage for efforts to find evidence-based solutions.
“When I became a pediatrician, I never thought that I would care for so many children who had been shot,” Andrews said. “It’s not something that you think about when you consider what a pediatrician does, but as a hospital-based doctor for the past 12 years I’ve seen it happen again and again. And I started to get really worried about this.”
When Andrews and her team looked at the data, they saw that gun-related deaths in children surpassed deaths caused by motor vehicle collisions beginning in 2019. And while the death rate due to car accidents has steadily declined since 2001, the firearm death rate has continued to climb, with increased homicide and suicide rates driving a 14% total increase over the last two decades.