It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Friday, December 04, 2020
Older adults in wealthier countries drink more alcohol
COLUMBIA UNIVERSITY'S MAILMAN SCHOOL OF PUBLIC HEALTH
A new global study finds older people in wealthy countries consume more alcohol than their counterparts in middle-income countries, on average, although a higher cost of alcohol is associated with less frequent drinking. Across counties, people drink less as they get older, but at different rates and starting points. The study was led by researchers at Columbia University Mailman School of Public Health and the Robert N. Butler Columbia Aging Center. Findings are published in the journal Addiction.
Alcohol consumption among older adults is trending higher across numerous countries, and alcohol use disorders among adults 65 and older have more than doubled in the last ten years. Moreover, there are signs that alcohol consumption is further increasing during the pandemic. Age-related changes that slow metabolism and increase the odds of medication interactions make alcohol consumption likely more harmful among older than younger adults.
The researchers analyzed survey data collected from 100,000 individuals age 50 and older in 17 countries in Europe, as well as China, Mexico, Israel, South Korea, and the United States. Average weekly alcohol consumption ranged from 0.59 units in Mexico to 6.85 units in the Netherlands. In the United States, older adults consumed 2.07 standard units per week. One standard unit is equivalent to a small shot glass of vodka or a 12oz glass of 5 percent beer.
The price of alcohol--measured by the cost of a bottle of red label Smirnoff vodka--varied from a low of $7.92 in Mexico to $38.06 in Ireland (4.96 standard units/week).
In most countries drinking decreased with age (U.S., China, Chile), but some countries had sharper age-related decreases (England, Ireland, Czech Republic) and others were fairly stable and had brief increases in drinking after age 50 (Denmark, France). This variation across age and countries is explained both by the health and socioeconomic status of older adults living in each country and country-level factors like economic development and alcohol prices.
Heavy drinking among older adults was highest in the Czech Republic and lowest in Israel, with levels of heavy drinking in most countries declining by age or slightly increasing then declining by older ages. Economic development and the cost of alcohol did not influence levels of heavy drinking, which may be driven by factors such as gender and cultural norms. Heavy drinking is defined for men as having more than three drinks per day or binging more than five drinks in a single occasion, and for women as having more than two drinks per day or binging more than four drinks in a single occasion.
"Public concern over drinking largely focuses on young people, but alcohol is also a serious threat to the health of older adults. In fact, the majority of alcohol-related deaths occur among older people," says first author Esteban Calvo, PhD, assistant professor of epidemiology in the Robert N. Butler Columbia Aging Center. "While some studies purport to show a benefit to drinking in old age, these findings are likely distorted by the fact that older drinkers tend to remain drinking if they are healthy, while recent abstainers (as opposed to lifetime abstainers) may only quit when they are sick."
"As countries develop economically and older people living there can afford to drink more, these countries should consider policies to regulate alcohol consumption, potentially combining minimum alcohol prices, taxation, sale and marketing regulations, and cessation programs," adds senior author Katherine M. Keyes, PhD, associate professor of epidemiology at Columbia Mailman School.
VIDEO: PARHYALE HAWAIENSIS, SHOWN HERE EATING, HAS HAD ITS GENOME SEQUENCED AND IS THE MOST GENETICALLY TRACTABLE CRUSTACEAN FOR BIOLOGICAL RESEARCH. view more
CREDIT: HEATHER BRUCE
WOODS HOLE, Mass. - It sounds like a "Just So Story" - "How the Insect Got its Wings" - but it's really a mystery that has puzzled biologists for over a century. Intriguing and competing theories of insect wing evolution have emerged in recent years, but none were entirely satisfactory. Finally, a team from the Marine Biological Laboratory (MBL), Woods Hole, has settled the controversy, using clues from long-ago scientific papers as well as state-of-the-art genomic approaches. The study, conducted by MBL Research Associate Heather Bruce and MBL Director Nipam Patel, is published this week in Nature Ecology & Evolution.
Insect wings, the team confirmed, evolved from an outgrowth or "lobe" on the legs of an ancestral crustacean (yes, crustacean). After this marine animal had transitioned to land-dwelling about 300 million years ago, the leg segments closest to its body became incorporated into the body wall during embryonic development, perhaps to better support its weight on land. "The leg lobes then moved up onto the insect's back, and those later formed the wings," says Bruce.
One of the reasons it took a century to figure this out, Bruce says, is that it wasn't appreciated until about 2010 that insects are most closely related to crustaceans within the arthropod phylum, as revealed by genetic similarities.
"Prior to that, based on morphology, everyone had classified insects in the myriapod group, along with the millipedes and centipedes," Bruce says. "And if you look in myriapods for where insect wings came from, you won't find anything," she says. "So insect wings came to be thought of as 'novel' structures that sprang up in insects and had no corresponding structure in the ancestor -- because researchers were looking in the wrong place for the insect ancestor."
"People get very excited by the idea that something like insect wings may have been a novel innovation of evolution," Patel says. "But one of the stories that is emerging from genomic comparisons is that nothing is brand new; everything came from somewhere. And you can, in fact, figure out from where."
Bruce picked up the scent of her now-reported discovery while comparing the genetic instructions for the segmented legs of a crustacean, the tiny beach-hopper Parhyale, and the segmented legs of insects, including the fruit fly Drosophila and the beetle Tribolium. Using CRISPR-Cas9 gene editing, she systematically disabled five shared leg-patterning genes in Parhyale and in insects, and found those genes corresponded to the six leg segments that are farthest from the body wall. Parhyale, though, has an additional, seventh leg segment next to its body wall. Where did that segment go, she wondered? "And so I started digging in the literature, and I found this really old idea that had been proposed in 1893, that insects had incorporated their proximal [closest to body] leg region into the body wall," she says.
"But I still didn't have the wing part of the story," she says. "So I kept reading and reading, and I came across this 1980s theory that not only did insects incorporate their proximal leg region into the body wall, but the little lobes on the leg later moved up onto the back and formed the wings. I thought, wow, my genomic and embryonic data supports these old theories."
It would have been impossible to resolve this longstanding riddle without the tools now available to probe the genomes of a myriad of organisms, including Parhyale, which the Patel lab has developed as the most genetically tractable research organism among the crustaceans.
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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.
CAPTION
Injection of CRISPR solution into crustacean embryos (Parhyale hawaiiensis).
CAPTION
Insects incorporated two ancestral crustacean leg segments (labeled 7 in red and 8 in pink) into the body wall. The lobe on leg segment 8 later formed the wing in insects, while this corresponding structure in crustaceans forms the tergal plate.
CREDIT
Heather Bruce
Clothing, tattoos could be used to monitor patient health
Emerging wearable technology uses tiny fibers that can track your blood pressure, heart rate, and more
IMAGE: MICROFIBER- AND NANOFIBER-BASED WEARABLE TECHNOLOGY CAN BE USED TO MONITOR A PATIENT'S VITAL SIGNS AT ALL TIMES. view more
CREDIT: NATIONAL UNIVERSITY OF SINGAPORE
WASHINGTON, December 1, 2020 -- A shirt that monitors your blood pressure or a pair of socks that can keep track of your cholesterol levels might be just a few years away from becoming reality.
In an article published in Applied Physics Reviews, by AIP Publishing, researchers examine the use of microfibers, and even smaller nanofibers, as wearable monitors that could keep track of a patient's vital signs.
The microfiber- and nanofiber-based technology addresses growing concerns in the medical community about monitoring chronic illnesses like diabetes, asthma, obesity, and high blood pressure as the population ages.
"Therefore, the demand for a personalized health care system which detects users' bio-signals at any given location and time is rapidly growing," said author Rituparna Ghosh.
The wearable fibers are highly sensitive and flexible and can be used to gauge blood pressure, heart rate, sleep quality, cholesterol levels, oxygen levels, and other vital signs. Because of their small size, they can be applied directly to the skin or woven into garments like shirts, socks, neckwear, or wristbands.
"You could have watches. You could have tattoos. It is usable in almost any form," said Ghosh. "You could have something like a face mask. It could be a handkerchief which you put on your wrist and it starts giving data."
Author Seeram Ramakrishna, from the National University of Singapore, said one of the most promising nanofiber technologies -- piezoelectric sensors, which are powered by mechanical energy -- could be ready to go to market in less than three years.
Other technologies, he said, may be ready for public use in anywhere from five to eight years.
Between now and then, Ramakrishna said more research needs to be done on making the fiber sensors more durable, so they can be used repeatedly, and coming up with a power source for them that is both reliable and portable. It also will take time, he said, to assure the medical community that the technology is accurate, and its data can be trusted for use with real-world patients.
"The medical community is always skeptical, while the wellness industry already is using these concepts," he said. "We need a lot more cause-and-effect studies. We need to amass information so doctors will really accept that this is information they can rely on."
The global market value of wearable technology was estimated to be more than $32 billion in 2019 and is expected to jump to as much as $74 billion by 2025 as new applications continue to emerge.
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The article, "Micro/nano fiber-based non-invasive devices for health monitoring diagnosis and rehabilitation," is authored by Rituparna Ghosh, Koh Yi Pin, Vundrala Sumedha Reddy, W.A.D.M. Jayathilaka, Dongxiao Ji, William Serrano-GarcÃa, Suresh K. Bhargava, Seeram Ramakrishna, and Amutha Chinappan. The article will appear in Applied Physics Reviews on Dec. 1, 2020 (DOI: 10.1063/5.0010766). After that date, it can be accessed at https://aip.scitation.org/doi/10.1063/5.0010766.
ABOUT THE JOURNAL
Applied Physics Reviews features articles on significant and current topics in experimental or theoretical research in applied physics, or in applications of physics to other branches of science and engineering. The journal publishes both original research on pioneering studies of broad interest to the applied physics community, and reviews on established or emerging areas of applied physics. See https://aip.scitation.org/journal/are.
Mailman School experts contribute to new Lancet report on health and climate change
Assessment finds millions of lives can be saved with climate action; COVID-19 shows everyone is vulnerable to converging health crises
COLUMBIA UNIVERSITY'S MAILMAN SCHOOL OF PUBLIC HEALTH
December 4, 2020 -- Unless we take urgent action to tackle climate change, we can expect an ever-hotter world that threatens global health, disrupts lives and livelihoods and overwhelms healthcare systems, according to The Lancet's Global Countdown on Health and Climate Change, a comprehensive global analysis tracking the impact of climate change on human health across 41 key indicators.
Experts from institutions across the globe who work at the nexus of climate change and health contributed to the published findings, including faculty from Columbia University Mailman School of Public Health. While the report presents the most worrying outlook to date as key trends worsen, the collaborators also find that with urgent climate action and a holistic response to the converging crises, the lives of millions can be improved and saved.
The 41 indicators are organized across five categories: 1) climate change impacts, exposures and vulnerabilities; 2) adaptation planning and resilience for health; 3) mitigation actions and health co-benefits; 4) economics and finance; and 5) public and political engagement.
Jeffrey Shaman, PhD, professor of environmental health sciences, director of the climate and health program and vice chairman of Columbia's Climate School, was a report contributor and reviewer. Lewis Ziska, PhD, associate professor of environmental health sciences, contributed to the chapter on food insecurity following extreme climate events where he also addressed structural and social determinants of food insecurity. "An important aspect of public health involves ensuring food security following a climate change induced extreme event. Here we look for common occurrences, problems and potential solutions that can be used as recommendations to ensure that no one goes hungry following a hurricane, flood or intense windstorm. But more needs to be done," noted Ziska.
According to Kim Knowlton, DrPH, assistant professor of environmental health sciences at Columbia Mailman and senior scientist, Natural Resources Defense Council, "This year's Lancet Countdown is the latest warning that the U.S. is going in the wrong direction on climate change and health. But it's not too late to change course. The incoming Biden/Harris administration should seize this opportunity to embrace the knowledge, expertise, and passion of the American public health and healthcare community. Together, we can build back a healthier, more equitable, and climate-resilient nation."
"Whether it's the spread of viruses and infectious diseases, heat exposure, or wildfires, the 2020 Lancet Countdown on Health and Climate Change U.S. Policy Brief shows how climate change makes communities and health care systems more vulnerable. The Brief lays out how climate action across sectors will lead to major environmental and public health gains," said Brittany Shea, Project Director, Global Consortium on Climate & Health Education, Columbia University Mailman School of Public Health.
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Columbia University Mailman School of Public Health
Founded in 1922, the Columbia University Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Columbia Mailman School is the seventh largest recipient of NIH grants among schools of public health. Its nearly 300 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change and health, and public health preparedness. It is a leader in public health education with more than 1,300 graduate students from 55 nations pursuing a variety of master's and doctoral degree programs. The Columbia Mailman School is also home to numerous world-renowned research centers, including ICAP and the Center for Infection and Immunity. For more information, please visit http://www.mailman.columbia.edu.
Rock-a-bye fly: Why vibrations lead to sleepiness
Researchers discover that gentle vibration can induce sleep in flies through a simple form of learning
CREDIT: IMAGE CREDIT: DR. KYUNGHEE KOH, THOMAS JEFFERSON UNIVERSITY.
PHILADELPHIA - It is common practice to rock babies to sleep. Children and grownups also get drowsy during long car rides. There is something about gentle mechanical stimuli that makes humans of all ages sleepy. Sleep in fruit flies is very much like human sleep, and you can learn a lot about human sleep by studying how fly sleep is regulated. In research published in Cell Reports on December 1st, 2020, researchers report that flies fall asleep during vibration through a simple form of learning called habituation.
"Babies like to be rocked to sleep, but the neural mechanisms underlying this well-known phenomenon remain largely a mystery. We wanted to establish the fruit fly as a model system to study the mechanisms of sleep induction by mechanical stimulation," says Kyunghee Koh, PhD, associate professor of neuroscience at the Vickie & Jack Farber Institute for Neurosciences and the Synaptic Biology Center at Thomas Jefferson University and senior author on the study.
The researchers found that flies sleep longer during vibration and are less responsive to light pulses that would otherwise wake the flies. Also, they are more awake after vibration, suggesting they have accumulated "sleep credit." In other words, they act as if they slept more than they need to during vibration, which allows them to function well with less sleep afterward.
These findings suggest that vibration-induced sleep is similar to regular sleep and serves some of their vital functions. They found that how much extra sleep flies get during vibration depends on the flies' genetic background as well as the vibration frequency and amplitude. Dr. Koh's group also learned that multiple sensory organs are involved in the process.
Interestingly, vibration initially makes flies more active than usual, but gradually puts them to sleep. Also, the ability to go to sleep improves when exposure to vibration is repeated several times, implicating habituation, a form of simple learning. "Flies learn over time that vibration is not threatening, which lowers their reaction to stimulation that would otherwise make them alert," says Dr. Koh. Suppression of alertness appears necessary for vibration-induced sleep because mutant flies with increased dopamine levels that make them more alert do not fall asleep with vibration.
It is yet unclear whether similar mechanisms are at work in humans. But Dr. Koh says, "further investigation may help us develop and optimize sensory stimulation as a sleep aid for humans. Our findings suggest it would be worthwhile to personalize the stimulus parameters for each individual over several sessions."
However, her team's initial goals are to learn more about the underlying neural mechanisms using the fruit fly as a model system. They plan to identify specific neurons in the fly brain involved in the process and determine whether vibration-induced sleep functions like normal sleep to enhance memory and longevity and whether repetitive stimulation of other senses (e.g., sight and smell) can also induce sleep.
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This work was supported by NIH grants R01NS086887 and R01NS084835, a predoctoral fellowship from the Portuguese Foundation for Science and Technology, and funds from Jefferson Synaptic Biology Center.
Article Reference: Arzu Öztürk-Çolak, Sho Inami, Joseph R. Buchler, Patrick D. McClanahan, Andri Cruz, Christopher Fang-Yen, and Kyunghee Koh, "Sleep Induction by Mechanosensory Stimulation in Drosophila," Cell Reports, DOI: 10.1016/j.celrep.2020.108462, 2020.
Dolutegravir, the current first-line treatment for HIV, may not be as effective as hoped in sub-Saharan Africa, suggests new research published on World AIDS Day. The study finds that this so-called 'wonder drug' may be less effective in patients resistant to older drugs.
As HIV copies itself and replicates, it can develop errors, or 'mutations', in its genetic code (its RNA). While a drug may initially be able to supress or even kill the virus, certain mutations can allow the virus to develop resistance to its effects. If a mutated strain begins to spread within a population, it can mean once-effective drugs are no longer able to treat people.
HIV treatment usually consists of a cocktail of drugs that includes a type of drug known as a non-nucleoside reverse-transcriptase inhibitor (NNRTI). However, in recent years, HIV has begun to develop resistance to NNRTIs. Between 10% and 15% of patients in much of sub-Saharan Africa are infected by a strain of HIV resistant to these drugs. If a patient is infected with an NNRTI-resistant strain, they are at a two- to three-fold increased risk of the drug regimen failing.
In 2019, the World Health Organization began to recommend dolutegravir as the preferred first-line treatment for HIV in most populations. Dolutegravir was dubbed a 'wonder drug' because it was safe, potent and cost-effective and scientists had seen no drug resistance against it in clinical trials. However, there is little data on the success of dolutegravir against circulating strains of HIV in sub-Saharan Africa.
In a study published today in Nature Communications, an international team of researchers from South Africa, the UK and the USA examined the genetic code of HIV to determine if drug resistance mutations in 874 volunteers living with HIV affected their treatment success. The individuals were enrolled in a clinical trial for people initiating HIV treatment to compare two drug regimens: efavirenz, an NNRTI and prior first-line therapy in the region, and dolutegravir.
The goal of this study was to determine whether drug resistance to efavirenz prior to starting treatment affected treatment success (suppression of the virus in the blood) over the first two years of therapy with both of these two regimens.
As expected, the presence of drug resistance substantially reduced the chances of treatment success in people taking efavirenz, successfully suppressing the virus over 96-weeks in 65% of participants compared to 85% of non-resistant individuals. However, unexpectedly, the same pattern was true for individuals taking dolutegravir-based treatments: 66% of those with efavirenz resistance mutations remained suppressed over 96-weeeks compared to 84% of those without the mutations. These relationships held true after accounting for other factors, such as treatment adherence.
"We fully expected efavirenz to be less effective among patients HIV strains resistant to NNRTIs," said Dr Mark Siedner, faculty member at the Africa Health Research Institute in KwaZulu-Natal, South Africa and Massachusetts General Hospital in Boston, Massachusetts. "What took us completely by surprise was that dolutegravir - a different class of drug which is generally effective in the face of drug resistance - would also be less effective in people with these resistant strains.
"We are working now to tease out if this was due to the virus or the participants - for instance, if people with resistance are less likely to take their pills regularly. Either way, if this pattern holds true, it could have far reaching impacts on our predictions of long-term treatment control for millions of people taking dolutegravir in the region."
Professor Ravi Gupta from the Department of Medicine at the University of Cambridge said: "This a huge concern. Dolutegravir was very much seen as a 'wonder drug', but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugs."
The researchers say it is not clear why efavirenz-resistant mutations should affect susceptibility of dolutegravir, though one hypothesis is that integrase inhibitors such as dolutegravir push the virus to replicate and mutate faster, in turn developing resistance to the new drug in an evolutionary arms race. Alternatively, it could be due to poor adherence to treatment regimens, even though the analysis accounted for adherence by two independent methods. Further research is needed to find out why.
Professor Gupta added: "What this shows is that we urgently need to prioritise point of care tests to identify people with drug resistance HIV, particularly against efavirenz, and to more closely and accurately monitor treatment adherence. The development of such tests is at an advanced stage, but there a lack of investment from funders and philanthropic donors. We urgently need agencies and individuals to step forward and help support these programmes.
"In addition, we need to provide widespread access to viral load monitoring so that we can find those who are struggling, get them on more appropriate regimens, and limit the emergence of resistance when patients are failing therapy."
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The study was carried out by researchers at: the Africa Health Research Institute, University of KwaZulu-Natal, University of Witwatersrand, KwaZulu-Natal Research Innovation and Sequencing Platform, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA), in South Africa; the University of Cambridge, University of Liverpool, and Imperial College London in the UK; and Massachusetts General Hospital and Harvard Medical School, USA.
The research was supported by USAID, Unitaid, the South African Medical Research Council (SAMRC), with investigational drug donated by ViiV Healthcare and Gilead Sciences, and by Wellcome and the National Institutes of Health.
Reference
Siedner, MJ et al. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat Comms; 1 Dec 2020; DOI: 10.1038/s41467-020-19801-x
CANCER NEWS
City of Hope developed cancer-killing virus: activates immune system against colon cancer
The preclinical research demonstrates that combining the oncolytic virus CF33 with an immune checkpoint inhibitor results in lasting resistance to certain tumors
DUARTE, Calif. -- A cancer-killing virus that City of Hope scientists developed could one day improve the immune system's ability to eradicate tumors in colon cancer patients, reports a new study in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.
The preclinical research is a first step to showing that City of Hope's oncolytic virus CF33 can target hard-to-treat tumors that "handcuff" the immune system and keep T cells from activating the immune system to kill cancer cells. More specifically, the researchers demonstrated in mouse models that CF33 appears to increase PD-L1 expression in tumor cells and causes them to die in a way that stimulates an influx of activated immune cells.
"CF33 is a safe, innovative virus City of Hope developed that can become a gamechanger because of how potent it is and because of its ability to recruit and activate immune cells," said Susanne Warner, M.D., a surgical oncologist at City of Hope and senior author of the study. "Our oncolytic virus trains the immune system to target a specific cancer cell. Preclinical models show that a combination treatment of oncolytic virus CF33 with anti-PD-L1 checkpoint inhibition leads to lasting anti-tumor immunity, meaning if a similar cancer cell ever tries to regrow, the immune system will be ready and waiting to shut it down."
Colorectal cancer is the third leading cause of cancer-related deaths in the United States and is expected to cause 53,200 deaths in 2020, according to the American Cancer Society. City of Hope researchers are excited about the potential of CF33 to enhance colon cancer treatment and point out that CF33 has been effective preclinically against a wide variety of cancers.
Yuman Fong, M.D., the Sangiacomo Family Chair in Surgical Oncology at City of Hope, and his team created oncolytic virus CF33 and expect to open a clinical trial to test the safety of this treatment in human patients in 2021. This treatment addresses a problem in cancer: Most solid tumors do not respond to checkpoint inhibitors because the "uncloaked tumor cell" still isn't recognized by the immune system, Fong said.
"CF33 selectively infects, replicates in and kills cancer cells. This study demonstrates that a designer virus we created to infect a wide variety of cancers can make tumor cells very recognizable to the immune system," Fong said. He, Warner and other City of Hope physician-scientists are working on turning "cold tumors" resistant to treatment into "hot tumors" that can be killed by a well-trained immune system.
The U.S. Food and Drug Administration has approved only one oncolytic virus thus far: T-VEC, which is a local immunotherapy treatment that kills melanoma cells.
To confirm their hypothesis, City of Hope scientists tested four groups: control with no treatment, anti-PD-L1 alone, CF33 alone, and a combination of CF33 and anti-PD-L1. Results indicated that a combined treatment of City of Hope's oncolytic virus and anti-PD-L1 appeared to be most effective. It also increased CD8+ T cells, which are immune cells that remember previous diseases and are trained to kill them if they are reintroduced later. In other words, the models developed anti-tumor immunity. This means that animals cured of their cancer were effectively immune to future tumor growth.
Fong and colleagues have demonstrated CF33's anti-tumor immune efficacy against triple-negative breast cancer cell lines, in brain tumor cells, in liver cancer models, and in pancreatic, prostate, ovarian, lung and head and neck cancer. Moreover, a recent City of Hope-led study found that CF33 could be combined with chimeric antigen receptor (CAR) T cell therapy to target and eliminate solid tumors that are otherwise difficult to treat with CAR T therapy alone. City of Hope has licensed CF33 to Imugene Limited, a company developing novel therapies that activate the immune system against cancer.
Notably, the CF33 virus may be tracked by non-invasive PET scanning. "If we can perfect the technique, we can give someone a viral injection and watch it work - see where it goes and identify cancer cells that we didn't even know existed," Warner said. "Doctors would have real-time data and know if we should give a patient a higher dose or where to direct the treatment based on tumors that have not yet been killed."
What Warner describes is a developing field called theranostic precision medicine, meaning doctors are able to give patients therapies and concurrently diagnose them to provide the most appropriate treatment for that patient. It is one of many precision medicine approaches City of Hope is developing and offering to patients.
The next step for the current study is to test the innovative CF33 virus platform in different solid tumor models.
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This research was supported by the American Cancer Society Mentored Research Scholar Grant (MRSG-16-047-01-MPC) and through the generosity of the Natalie and David Roberts Family.
About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope's translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nation's "Best Hospitals" in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
AI predicts which drug combinations kill cancer cells
A machine learning model developed in Finland can help us treat cancer more effectively
IMAGE: AI METHODS CAN HELP US PERFECT DRUG COMBINATIONS. view more
CREDIT: MATTI AHLGREN, AALTO UNIVERSITY
When healthcare professionals treat patients suffering from advanced cancers, they usually need to use a combination of different therapies. In addition to cancer surgery, the patients are often treated with radiation therapy, medication, or both.
Medication can be combined, with different drugs acting on different cancer cells. Combinatorial drug therapies often improve the effectiveness of the treatment and can reduce the harmful side-effects if the dosage of individual drugs can be reduced. However, experimental screening of drug combinations is very slow and expensive, and therefore, often fails to discover the full benefits of combination therapy. With the help of a new machine learning method, one could identify best combinations to selectively kill cancer cells with specific genetic or functional makeup.
Researchers at Aalto University, University of Helsinki and the University of Turku in Finland developed a machine learning model that accurately predicts how combinations of different cancer drugs kill various types of cancer cells. The new AI model was trained with a large set of data obtained from previous studies, which had investigated the association between drugs and cancer cells. 'The model learned by the machine is actually a polynomial function familiar from school mathematics, but a very complex one,' says Professor Juho Rousu from Aalto University.
The research results were published in the prestigious journal Nature Communications, demonstrating that the model found associations between drugs and cancer cells that were not observed previously. 'The model gives very accurate results. For example, the values ??of the so-called correlation coefficient were more than 0.9 in our experiments, which points to excellent reliability,' says Professor Rousu. In experimental measurements, a correlation coefficient of 0.8-0.9 is considered reliable.
The model accurately predicts how a drug combination selectively inhibits particular cancer cells when the effect of the drug combination on that type of cancer has not been previously tested. 'This will help cancer researchers to prioritize which drug combinations to choose from thousands of options for further research,' says researcher Tero Aittokallio from the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki.
The same machine learning approach could be used for non-cancerous diseases. In this case, the model would have to be re-taught with data related to that disease. For example, the model could be used to study how different combinations of antibiotics affect bacterial infections or how effectively different combinations of drugs kill cells that have been infected by the SARS-Cov-2 coronavirus.
Cancer cases are rising in adolescents and young adults
HERSHEY, Pa. -- Cancer cases in adolescents and young adults have risen by 30% during the last four decades, with kidney cancer rising at the greatest rate, according to researchers at Penn State College of Medicine. The team said further research into screening, diagnosis and treatment are needed to address the growing trend in this age group.
Dr. Nicholas Zaorsky, assistant professor of radiation oncology and public health sciences, said that cancer is the leading cause of disease-related death in this age group and that the increasing number of cases is concerning.
"Adolescents and young adults are a distinct cancer population," Zaorsky said. "But they are often grouped together with pediatric or adult patients in research studies. It is important to study how this group is distinct so that care guidelines can be developed to address the increase in cases."
The researchers analyzed data -- including sex, age at diagnosis and type of cancer -- from nearly half a million cancer patients in the United States between 15 and 39 years old across more than four decades. The data were collected by the National Cancer Institute's Surveillance, Epidemiology and End Results Program. The team's goal was to determine the number of cancer cases in adolescents and young adults between 1973 and 2015. The results published today (Dec. 1) in JAMA Network Open.
During the time period studied, the researchers found cancer diagnoses increased from 57 to 74 per 100,000 adolescents and young adults. The most common types in males were testicular, melanoma and non-Hodgkin lymphoma. The most common types in females were breast, thyroid, cervical and uterine cancers. Zaorsky, a Penn State Cancer Institute researcher, said that the rates of kidney, thyroid and gastrointestinal cancers are increasing in this age group.
"Other studies have shown these types are increasing among this age group," said Zaorsky. "Our data reinforces the fact that clinicians should be on the lookout for these cancers in their adolescent and young adult patients."
According to Zaorsky, further research is needed to determine why kidney, thyroid, gastrointestinal and other types of cancer are on the rise in adolescents and young adults. He said that environmental, dietary and screening changes during the time period studied may have contributed to the increased incidences.
"These cancers all have unique risk factors," Zaorsky said. "Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed."
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Alyssa Scott, Kelsey Stoltzfus, Leila Tchelebi and Pooja Rao of Penn State College of Medicine; Daniel Trifiletti of Mayo Clinic; Eric Lehrer of Icahn School of Medicine at Mount Sinai; and Archie Bleyer of Oregon Health and Science University and McGovern Medical School also contributed to this research.
This research was supported by the National Center for Advancing Translation Sciences (Grants TL1 TR002016 and UL1 TR002014) through Penn State Clinical and Translational Science Institute's Translational Science Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors disclose no conflict of interest.
PHILADELPHIA (December 1, 2020) - More than 90 percent of human papillomavirus (HPV)-related cancers could be prevented by widespread uptake of the HPV vaccine. Yet, vaccine use in the United States falls short of public health goals.
In an article in JMIR Nursing, researchers explain how they applied user-centered design principles to develop a mobile health (mhealth) app to improve HPV vaccine uptake and how its use was evaluated with parents and parent-adolescent dyads. The app -- Vaccipack -- is exclusively focused on adolescent vaccines and targets key parental beliefs related to HPV vaccines. The mhealth app is designed for parents (to use and share with their adolescents) to promote the initiation and completion of the HPV vaccine series in their adolescent children.
The study from the University of Pennsylvania School of Nursing (Penn Nursing) evaluated the acceptability of and intention to use the app. It found that intention to use the app was high among both parents and adolescents after being introduced to the app and given time explore it.
"Theory-based content design, although standard practice in behavioral intervention research, has not been a typical approach adopted by app developers," says Anne M. Teitelman, PhD, FNP-BC, FAANP, FAAN, Associate Professor Emerita of Nursing at Penn Nursing. "Evaluation of acceptability and likely use, as we present here, is an important preliminary step for developing apps and in designing behavioral interventions that are most likely to achieve the desired health outcome." Teitelman is the lead investigator of the study and among the developers of the app.
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The article, "Vaccipack, A Mobile App to Promote Human Papillomavirus Vaccine Uptake Among Adolescents Aged 11 to 14 Years: Development and Usability Study" is available online.
Coauthors of the article include Joshua Jayasinghe, BSN, PhD; Ja H. Koo1, BSN; and Annet Davis, RN, MSW, all of Penn Nursing; Emily F. Gregory MD, MHS and Kristen A. Feemster, MD, MPH, MSHP, both of the Children's Hospital of Philadelphia; Zara Wermers of xTufts University; Jennifer F. Morone, RN, MA-ATR, PhD of Yale University; and Damien C. Leri, MPH, MS-Ed of Big Yellow Star, Inc.
