Publisher Health

Equipping cancer-infecting, or oncolytic, viruses with tumor-inhibiting genetic cargo stimulates the immune system and helps immunotherapy to shrink or completely clear aggressive tumors in mice, according to a new study in the Journal of Experimental Medicineled by University of Pittsburgh and UPMC researchers. The results pave the way for clinical trials combining oncolytic viruses with immunotherapy.
Oncolytic viruses are genetically modified viruses that target rapidly dividing tumor cells while avoiding normal cells. Oncolytic viruses were originally designed to directly kill cancer cells, but researchers later noticed that they also stimulated the immune system, suggesting that they could be coupled with other cancer therapies such as immune checkpoint inhibitors, which remove the brakes on the immune system so that T cells can recognize and attack tumors.
“Immune checkpoint inhibitors work only in ‘hot’ tumors, which have already been infiltrated by T cells,” said senior author Greg Delgoffe, Ph.D., associate professor of immunology at Pitt’s School of Medicine and director of the Tumor Microenvironment Center at UPMC Hillman Cancer Center. “Oncolytic viruses can help ‘warm up’ cold tumors, so they have amazing potential to work hand-in-hand with immunotherapy, but they haven’t yet lived up to that promise.”
According to lead author Kristin DePeaux, a graduate student in Delgoffe’s lab, the problem is that many patients’ tumors do not respond to oncolytic viruses.
“There’s been a lot of interesting lab-based research on oncolytic viruses, but it hasn’t translated to the clinic,” she said. “We wanted to understand the mechanisms behind tumor resistance to these viruses to see what we can do to help patients.”
The researchers first developed a head-and-neck squamous cell carcinoma (HNSCC) cell line that is very sensitive to an oncolytic virus called vaccinia. Tumors injected with the virus regress after a single dose. They also developed a second cancer cell line that was otherwise identical but resistant to vaccinia.
After injecting both types of cells into mice and comparing immunological differences in the tumors that grew, they found that resistance to vaccinia was driven by high levels of a signaling protein called TGF-?, which is known to promote cancer growth by suppressing the immune environment.

Older adults who play digital puzzle games have the same memory abilities as people in their 20s, a new study has shown.
The study, from the University of York, also found that adults aged 60 and over who play digital puzzle games had a greater ability to ignore irrelevant distractions, but older adults who played strategy games did not show the same improvements in memory or concentration.
It is known that as humans age, their mental abilities tend to decrease, particularly the ability to remember a number of things at a single time — known as working memory. Working memory is thought to peak between the ages of 20 and 30 before slowly declining as a person gets older.
Previous research, however, has shown that the way we hold information in the brain changes as we get older, and so the York team looked at whether the impacts of particular types of mental stimulation, such as gaming, also had altered effects depending on age.
Dr Fiona McNab, from the University of York’s Department of Psychology, said: “A lot of research has focused on action games, as it is thought that reacting quickly, keeping track of targets and so on helps attention and memory, but our new analysis shows that the action elements do not seem to offer significant benefits to younger adults.
“It instead seems to be the strategy elements of the games — planning and problem solving for example — that stimulates better memory and attention in young people. We don’t see this same effect in older adults, however, and more research is needed to understand why this is. We can’t yet rule out that the strategy games played by older people are not as difficult as the games played by younger people and that the level of challenge might be important in memory improvement.”
The study included older and younger adults playing digital games that they would normally play in their ‘real lives’. This resulted in a wide range of games to be tested alongside a digital experiment that required participants to memorise images, whilst being distracted.

A deafened adult cannot recover the ability to hear, because the sensory hearing cells of the inner ear don’t regenerate after damage. In two new studies, partially funded by the National Institutes of Health and published in the Proceedings of the National Academy of the Sciences (PNAS), USC Stem Cell scientists explain why this is the case and how we might be able to change it.
“In the non-sensory supporting cells of the inner ear, key genes required for conversion to sensory cells are shut off through a process known as ‘epigenetic silencing.’ By studying how the genes are shut off, we begin to understand how we might turn them back on to regenerate hearing,” said John Duc Nguyen, the first author of one of the papers. Nguyen now works at the biotech company Genentech and earned his PhD in the USC Stem Cell laboratory of Neil Segil, who passed away from pancreatic cancer in 2022.
The second paper explored when and how the ability to form sensory hearing cells is gained in the inner ear in the first place and describes two specific genes that could be useful for regenerating hearing in adults.
“We focused on the genes Sox4 and Sox11 because we found that they are necessary for forming sensory hearing cells during development,” said the paper’s first author Emily Xizi Wang, who also conducted her research as a PhD student in the Segil Lab and works at the biotech company Atara Biotherapeutics.
Gage Crump, a co-author on both papers and the interim chair of USC’s Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, added: “These two papers are not only great science, but also a clear example of Neil Segil’s enduring legacy as an exceptional mentor to the next generation of stem cell researchers.”
Silencing isn’t golden
One important way that genes are shut off or “silenced” involves chemical compounds called methyl groups that bind to DNA and make it inaccessible — the focus of Nguyen’s paper. When the DNA that instructs a cell to become a sensory hearing cell is methylated, the cell cannot access these instructions.

Scientific journals and research papers are evaluated by a metric known as their “impact factor,” which is based on how many times a given paper is cited by other papers. However, a new study from MIT and other institutions suggests that this measure does not accurately capture the impact of medical papers on health outcomes for all patients, particularly those in low- or middle-income countries.
To more fully capture a paper’s impact on health, metrics should take into account the demographics of the researchers who performed the studies and the patients who participated in them, the research team says. To that end, they have developed a metric that they call the “diversity factor.”
The new metric incorporates several factors, including the diversity of the paper authors (in terms of gender and geographic location), diversity of the patients studied, and how interdisciplinary the research team is. In a new study, the researchers evaluated more than 100,000 medical papers published in the last 20 years and found that most did not do well on this metric.
“The medical knowledge system is controlled by a very noninclusive group of academics, and it’s not diverse at all,” says Leo Anthony Celi, a senior research scientist at MIT’s Institute for Medical Engineering and Science, a physician at Beth Israel Deaconess Medical Center, an associate professor at Harvard Medical School,and one of the authors of the paper.
The researchers hope that their new study will generate more discussion of how to evaluate medical papers and make sure they are contributing to positive health outcomes for diverse populations, not just the groups who have traditionally led and been the subjects of medical studies.
Jack Gallifant, a physician at Imperial College London NHS Trust, led the new study, which appears today in PLOS Global Public Health. The authors also include researchers from institutions around the world, including Mbarara University of Science and Technology in Uganda, National Polytechnic Institute in Mexico, University of the Philippines at Manila, the University of Witwatersrand in South Africa, Handong Global University in South Korea, and King Hussein Cancer Center in Jordan, and representing the fields of public health, pharmacy, medicine, computer science, engineering and the social sciences.
“Blind spots” in medical knowledge
Celi and his colleagues began developing the new index in hopes of finding ways to document and combat the lack of diversity among authors of prominent medical publications. Most of these authors come from wealthy nations including the United States, and they are disproportionately white and male.

Scientists have completed a deep analysis of the proteins driving cancer across multiple tumor types, information that can’t be assessed by genome sequencing alone. Understanding how proteins operate in cancer cells raises the prospect of new therapies that block key proteins that drive cancer growth, or therapies that trigger immune responses to abnormal proteins created by cancer cells.
Led by Washington University School of Medicine in St. Louis, the Broad Institute of MIT and Harvard, Brigham Young University and other institutions around the world, the Clinical Proteomic Tumor Analysis Consortium investigates key proteins driving cancer and how they’re regulated.
The findings are published Aug. 14 in a set of papers in the journals Cell and Cancer Cell.
The Clinical Proteomic Tumor Analysis Consortium is funded by the National Cancer Institute of the National Institutes of Health (NIH).
“In our efforts to develop better cancer therapies, this new analysis of the proteins driving tumor growth is the next step after cancer genome sequencing,” said senior author Li Ding, PhD, the David English Smith Distinguished Professor of Medicine at Washington University. “Through our past work sequencing the genomes of cancer cells, we identified almost 300 genes driving cancer. Now, we are studying the details of the machinery these cancer genes set in motion — the proteins and their regulatory networks that actually do the work of causing uncontrolled cell division. We are hopeful this analysis will serve as an important resource for cancer researchers seeking to develop new treatments for many tumor types.”
The researchers analyzed about 10,000 proteins involved in 10 different types of cancer. Ding emphasized the importance of the sheer volume of data in this type of analysis; many of these important cancer-driving proteins are rare in any single cancer and could not have been identified had the tumor types been studied individually. The analysis included two different types of lung cancer as well as colorectal, ovarian, kidney, head and neck, uterine, pancreatic, breast and brain cancers.
“Many of these proteins driving cancer are found in multiple tumor types but at low frequency,” said Ding, also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “When we analyze many cancer types together, we increase the power we have to detect important proteins that are causing the cancer to grow and spread. A combined analysis also allows us to pinpoint the major common mechanisms driving cancers across types.”
Beyond the function of individual proteins, such data also allow the researchers to understand how proteins interact with one another to fuel cancer growth. If the levels of two proteins correlate with one another — for example, when one is present at high levels and the other always is as well — this can indicate that the two proteins act as partners. Disrupting the interaction may be a promising way to block tumor growth.

In the rush to harness artificial intelligence and machine learning tools to make care more efficient at hospitals nationwide, a new study points to another possible use: identifying patients with non-medical needs that could affect their health and ability to receive care.
These social determinants of health — everything from transportation and housing to food supply and availability of family and friends as supports — can play a major role in a patient’s health and use of health care services.
The new study focuses on a patient population with especially complex needs: people with Alzheimer’s disease or other forms of dementia. Their condition can make them especially reliant on others to get them to medical appointments and social activities, handle medications and finances, shop and prepare food, and more.
The results of the study show that a rule-based natural language processing tool successfully identified patients with unstable access to transportation, food insecurity, social isolation, financial problems and signs of abuse, neglect, or exploitation.
The researchers found that a rule-based NLP tool — a kind of AI that analyzes human speech or writing — was far superior to deep learning and regularized logistic regression algorithms for identifying patients’ social determinants of health.
However, even the NLP tool did not do well enough at identifying needs related to housing or affording or taking medication.
The study was led by Elham Mahmoudi, Ph.D., a health economist at Michigan Medicine, the University of Michigan’s academic medical center, and Wenbo Wu, Ph.D., who completed the work while earning a doctorate at the U-M School of Public Health and is now at New York University. Mahmoudi and two other authors are in the Department of Family Medicine.

One of the biggest obstacles to the uptake of plant-based alternatives to meat is their very dry and astringent feel when they are eaten.
Scientists, led by Professor Anwesha Sarkar at the University of Leeds, are revolutionising the sensation of plant proteins, transforming them from a substance that can be experienced as gloopy and dry to one that is juicy and fat like.
And the only substance they are adding to the plant proteins is water.
Plant protein microgels
To bring about this change, the scientists created plant protein microgels, through a process called microgeletion.
Plant proteins — which start off as dry with a rough texture — are placed in water and subjected to heating. This alters the structure of the protein molecules which come together to form an interconnected network or gel which traps water around the plant proteins.
The gel is then homogenised, which breaks the protein network into a microgel made up of tiny particles that cannot be seen with the naked eye. Under pressure, as they would be when they are being eaten, the microgels ooze water, creating a lubricity akin to that of single cream.

A study published in Science indicates that climatic shifts over the past 400,000 years have influenced Neanderthal and Denisovan interbreeding.
Recent paleogenomic research revealed that interbreeding was common among early human species. However, little was known about when, where, and how often this hominin interbreeding took place. Using paleoanthropological evidence, genetic data, and supercomputer simulations of past climate, a team of international researchers has found that interglacial climates and corresponding shifts in vegetation created common habitats for Neanderthals and Denisovans, increasing their chances for interbreeding and gene flow in parts of Europe and central Asia.
Contemporary humans carry in their cells a small amount of DNA derived from Neanderthals and Denisovans. “Denny,” a 90,000-year-old fossil individual, recently identified as the daughter of a Denisovan father and a Neanderthal mother, bears testimony to the possibility that interbreeding was quite common among early human species. But when, where, and at what frequency did this interbreeding take place?
In a recent study published in Science on 10 August 2023, researchers from Korea and Italy have joined hands to answer this question. Using fossil data, supercomputer simulations of past climate, and insights obtained from genomic evidence, the team was able to identify habitat overlaps and contact hotspots of these early human species. Dr. Jiaoyang Ruan, Postdoctoral Researcher at IBS Center for Climate Physics (ICCP), South Korea, explains, “Little is known about when, where, and how frequently Neanderthals and Denisovans interbred throughout their shared history. As such, we tried to understand the potential for Neanderthal-Denisovan admixture using species distribution models that bring extensive fossil, archeological, and genetic data together with transient Coupled General Circulation Model simulations of global climate and biome.”
The researchers found that Neanderthals and Denisovans had different environmental preferences to start with. While Denisovans were much more adapted to colder environments, such as the boreal forests and the tundra region in northeastern Eurasia, their Neanderthal cousins preferred the warmer temperate forests and grasslands in the southwest. However, shifts in the Earth’s orbit led to changes in climatic conditions and hence vegetation patterns. This triggered the migration of both these hominin species towards geographically overlapping habitats, thus increasing the chance of their interbreeding.
The researchers further used insights gained from their analysis to determine the contact hotspots between Neanderthals and Denisovans. They identified Central Eurasia, the Caucasus, the Tianshan, and the Changbai mountains as the likely hotspots. Identification of these habitat overlaps also helped the researchers place ‘Denny’ within the climatic context and even confirmed the other known episodes of genetic interbreeding. The researchers also noted that the Denisovans and Neanderthals would have had a high probability of contact in the Siberian Altai during ~ 340-290, ~240-190 and ~130-80 thousand years ago.
To further elucidate the factors that triggered the ‘east-west interbreeding seesaw,’ the team examined the change in vegetation patterns over Eurasia over the past 400 thousand years. They observed that elevated atmospheric CO2 concentrations and mild interglacial conditions caused an eastward expansion of the temperate forest into central Eurasia, and the dispersal of Neanderthals into Denisovan lands. On the contrary, lower CO2 concentrations and corresponding harsher glacial climate potentially caused a fragmentation of their habitats, leading to lesser interactions and interbreeding events.
“Pronounced climate-driven zonal shifts in the main overlap region of Denisovans and Neanderthals in central Eurasia, which can be attributed to the response of climate and vegetation to past variations in atmospheric CO2 and northern hemisphere ice-sheet volume, influenced the timing and intensity of potential interbreeding events,” remarks senior author Axel Timmermann, Director, ICCP and Professor at Pusan National University, South Korea.
In summary, the study shows that climate-mediated events have played a crucial role in facilitating gene flow among early human species and have left lasting impressions on the genomic ancestry of modern-day humans.

Medical imaging via X-rays, CT scans, MRIs and ultrasounds provide health-care professionals with unique perspectives and a better understanding of what’s happening inside a patient’s body. Using various forms of waves, these machines can visualize many unseen ailments and diseases.
This imaging is beneficial for health-care professionals to make correct diagnoses, but the added insight of spectroscopy provides even more detail. Spectroscopy offers a means to identify biomolecules within specimens through their characteristic signatures for absorption in the electromagnetic spectrum.
Now, researchers at UBC Okanagan’s School of Engineering want to take that diagnostic imaging a step further.
By recognizing the benefits of imaging and spectroscopy, the researchers in UBCO’s Integrated Optics Laboratory (IOL) are now developing imaging systems that apply terahertz radiation. Terahertz radiation lies in the electromagnetic spectrum, with frequencies between radio and visible waves. This opens the door to fast and accurate terahertz characterizations of biological specimens — and can ultimately help with the creation of effective technologies for cancer detection.
“By working with terahertz radiation, we’re able to glean details on the underlying characteristics of biological specimens,” explains Alexis Guidi, a School of Engineering master’s student and lead author of a new study published in Scientific Reports. “This insight comes from the nature of terahertz radiation, which is intricately sensitive to the biomolecular make-up of cells.”
Nonetheless, according to Dr. Jonathan Holzman, IOL Principal Investigator and Electrical Engineering Professor, there are pressing challenges in developing these terahertz systems.
“The characteristics of terahertz radiation that make it an effective probe of biomolecules, in terms of its long wavelengths, also make it challenging to focus and resolve in images. Our recent work solved this by demonstrating terahertz spectroscopy can show a resolution approaching the cellular scale.”
The researchers plan on applying their findings in emerging areas of medical diagnoses, with a particular emphasis on carcinogenesis — the process by which healthy cells become cancerous.
The research is partially funded through support from the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation and Western Economic Diversification Canada.

Unexpected new insights into how COVID-19 infects cells may help explain why coronaviruses are so good at jumping from species to species and will help scientists better predict how COVID-19 will evolve.
Throughout the pandemic, there has been much discussion of how COVID-19 infiltrates cells by hijacking a protein called ACE2 found on human cells. But the new research from the School of Medicine reveals that ACE2 isn’t required for infection. Instead, the virus has other means it can use to infect cells.
That versatility suggests that coronaviruses can use multiple “doors” to enter cells, potentially explaining how they are so good at infecting different species.
“The virus that causes COVID-19 uses ACE2 as the front door to infect cells, but we’ve found that if the front door is blocked, it can also use the back door or the windows,” said researcher Peter Kasson, MD, PhD, of UVA’s Departments of Molecular Physiology and Biomedical Engineering. “This means the virus can keep spreading as it infects a new species until it adapts to use a particular species’ front door. So we have to watch out for new viruses doing the same thing to infect us.”
Understanding COVID-19
COVID-19 has killed almost 7 million people around the world. Thankfully, the availability of vaccines and the increase in population immunity means that the virus is no longer the threat it once was to most people (though it remains a concern for groups such as the immunocompromised and elderly). With the expiration of the United States’ official Public Health Emergency in May, most Americans have largely returned to lives similar to the ones they knew before the pandemic emerged in 2019. But COVID-19 continues to evolve and change, and scientists are keeping a close eye on it so that they can take quick action if a more dangerous variant emerges. They also continue to monitor other coronaviruses in case they jump to humans and become the next great public health threat.
As part of this effort, Kasson and his team wanted to better understand how the virus responsible for COVID-19, SARS-CoV-2, can enter human cells. Scientists have known that the virus essentially knocks on the cell’s door by binding to ACE2 proteins. These proteins are bountiful on the surfaces of cells lining the nose and lungs.