Publisher Health

Theory has it that disgust sensitivity — how intensely a person is repulsed by images, ideas or situations that could be considered terribly gross or merely unpleasant — is an evolutionary trait that initially helped humans avoid eating rotten food that would have made them sick.
Research has since shown that disgust sensitivity, as measured on a specific scale, can differ widely, with some individuals experiencing disgust very strongly and others less so. But the explanation for those differences is subject to debate. Is high disgust sensitivity the result of growing up with germophobes, related to neuroticism, or a way to detect an unfit sexual partner? And is disgust stable across the lifespan, or can it change?
A new study suggests disgust sensitivity can and does change — and, during the COVID-19 pandemic, concern about getting sick with a coronavirus infection was associated with an increase in disgust sensitivity.
Ohio State University researchers who had collected disgust sensitivity data for a larger project before the coronavirus outbreak compared those measures to similar data collected during and after pandemic lockdowns.
“What hasn’t been tested thoroughly is the extent to which your environment actually shapes your disgust sensitivity. What happens when you’re in an environment that has a lot of pathogens?” said Shelby Boggs, a doctoral student in psychology at The Ohio State University and first author of the study. “Disgust sensitivity was higher in studies we ran during the pandemic, but particularly higher for people who felt concerned they would actually contract COVID-19.”
Boggs conducted the study with senior author Russell Fazio, professor of psychology at Ohio State, and former postdoctoral researcher Benjamin Ruisch, who is now at Leiden University.

A new data portal called Cancer-Immu established by a team of Vanderbilt University Medical Center biostatisticians can help cancer clinicians and researchers predict which patients will respond to immune checkpoint inhibitors. With data from 3,652 samples for 16 cancer types, Cancer-Immu is the largest immune checkpoint blockade-related data portal for exploring immunogenomic connections.
The team provided details about the open-access portal in a paper published Dec. 13 in Cancer Research. Cancer-Immu integrates large-scale multidimensional omics data, including genetic, bulk, and single-cell transcriptomic, proteomic and dynamic genomic profiles. It also integrates clinical phenotypes.
While immune checkpoint inhibitors can be lifesaving for some patients with cancer, most patients do not respond to the immunotherapies. Researchers are working to identify biomarkers that predict response, and Cancer-Immu offers a comprehensive functional portal for unraveling immune-genomic connections.
“It provides easy access to immunogenic data and empowers researchers to translate omics datasets into biological insights and clinical applications,” said Yu Shyr, PhD, chair of the Department of Biostatistics at VUMC, Harold L. Moses Chair in Cancer Research and one of the paper’s senior authors. According to Qi Liu, PhD, associate professor of Biostatistics and the paper’s other senior author, “Cancer-Immu covers the greatest number of datasets and omics data types compared to existing databases with immune checkpoint blockade response outcome.”
The cancer types in the data portal include melanoma, non-small cell lung cancer, metastatic urothelial cancer, renal cell carcinoma, bladder cancer, glioma, colorectal cancer, head and neck cancer, esophagogastric cancer, cancer of unknown primary cause, gastric cancer, breast cancer, hepatocellular carcinoma, prostate cancer, basal cell carcinoma and non-melanoma skin cancer.
With the Cancer-Immu portal, clinicians and researchers can upload and analyze their own data or co-analyze with existing data simultaneously. They can use either a meta-analysis or a pan-cancer analysis. The portal has collections of three types of omics data: genetic, transcriptomics and single cell data. The pan-cancer module, which aggregates multiple datasets into one, enhances the detection and analysis of rare features. The biostatisticians noted in the study that while meta-analysis — the statistical evaluation of independent studies focused on the same question — failed to detect significant gene mutations, the pan-cancer analysis, which is a more expansive evaluation across multiple cancer types, detected 182 genes with mutations significantly associated with immune checkpoint inhibitors.
“Cancer-Immu helps address a lack and a challenge for evaluation of efficacy of known biomarkers and the discovery of new signatures,” said the study’s first author, Jing Yang, PhD, a postdoctoral fellow in the Shyr Research Lab.
The research that led to the establishment of Cancer-Immu was supported by the National Cancer Institute with SPORE in Gastrointestinal Cancer, SPORE in Breast Cancer, and Cancer Center Support Grant funding.
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Materials provided by Vanderbilt University Medical Center. Original written by Tom Wilemon. Note: Content may be edited for style and length.

A new experimental platform developed at Rice University promises to speed up the discovery of how infectious bacteria become resistant to antibiotics.
The microfluidic application by Rice bioscientist Yousif Shamoo and his team quickly encapsulates bacteria with varying concentrations of antibiotics to analyze how they evolve to become resistant.
The details appear in the American Chemical Society journal ACS Infectious Diseases.
“The idea of using microfluidics to encapsulate cells isn’t new; there are plenty of lab-on-a-chip devices already,” said Shamoo, who specializes in the study of multidrug-resistant bacteria. “What we’ve done is apply it to biomarker discovery for antibiotic resistance.”
The established technique for studying resistance involves feeding antibiotics in gradually increasing amounts to vials of bacteria in a solution. That reveals how some microbes evolve resistance, but favors mutants that grow fastest and makes it difficult to control other factors like population size, number of generations and the space they occupy, all of which can influence the evolutionary process.
Putting cells into microdroplets overcomes those limitations by allowing researchers to fine-tune their environments, allowing them to study new evolutionary trajectories.

Some patients who develop new cognitive symptoms after a mild bout of COVID have abnormalities in their cerebrospinal fluid similar to those found in people with other infectious diseases. The finding may provide insights into how SARS-CoV-2 impacts the brain.
In a small study with 32 adults, comprising 22 with cognitive symptoms and 10 control participants without, researchers from UC San Francisco and Weill Cornell Medicine, New York, analyzed the cerebrospinal fluid of 17 of the participants who consented to lumbar puncture. All participants had had COVID but had not required hospitalization.
They found that 10 of 13 participants with cognitive symptoms had anomalies in their cerebrospinal fluid. But all four of the cerebrospinal samples from participants with no post-COVID cognitive symptoms were normal. The research publishes on Jan. 18, 2022 in Annals of Clinical and Translational Neurology.
The average age of the participants with cognitive symptoms was 48, versus 39 for the control group. Participants with these symptoms presented with executive functioning issues, said senior author Joanna Hellmuth, MD, MHS, of the UCSF Memory and Aging Center. “They manifest as problems remembering recent events, coming up with names or words, staying focused, and issues with holding onto and manipulating information, as well as slowed processing speed,” she said.
“Brain fog” is a common after-effect of COVID, affecting some 67 percent of 156 patients at a post-COVID clinic in New York, a study published this month shows. In the current study, patients were enrolled in the Long-term Impact of Infection with Novel Coronavirus (LIINC) study that evaluates recovery in adults with confirmed SARS-CoV-2.
Examinations of the cerebrospinal fluid revealed elevated levels of protein, suggesting inflammation, and the presence of unexpected antibodies found in an activated immune system. Some were found in the blood and cerebrospinal fluid, implying a systemic inflammatory response, or were unique to the cerebrospinal fluid, suggesting brain inflammation. While the targets of these antibodies are unknown, it is possible that these could be “turncoat” antibodies that attack the body itself.

Blood drawn from patients shortly after they were infected with SARS-CoV-2, the virus that causes COVID-19, may indicate who is most likely to land in the hospital, a study led by Stanford Medicine investigators has found.
“We’ve identified an early biomarker of risk for progression to severe symptoms,” said Taia Wang, MD, PhD, assistant professor of infectious diseases and of microbiology and immunology. “And we found that antibodies elicited by an mRNA vaccine — in this case, Pfizer’s — differ in important, beneficial ways from those in people infected with SARS-CoV-2 who later progress to severe symptoms.” The upshot could eventually be a test that, given soon after a positive COVID-19 result, would help clinicians focus attention on those likely to need it most.
A paper describing the study’s findings was published Jan. 18 in Nature Immunology. Wang shares senior authorship with Gene Tan, PhD, assistant professor at the J. Craig Venter Institute in La Jolla, California. Lead co-authors of the study are Stanford postdoctoral scholar Saborni Chakraborty, PhD, and graduate student Joseph Gonzalez.
“Severe COVID-19 is largely a hyperinflammatory disease, particularly in the lungs,” Wang said. “We wondered why a minority of people develop this excessive inflammatory response, when most people don’t.”
To find out, Wang and her colleagues collected blood samples from 178 adults who had tested positive for COVID-19 upon visiting a Stanford Health Care hospital or clinic. At the time of testing, these individuals’ symptoms were universally mild. As time passed, 15 participants developed symptoms bad enough to land them in the emergency department.
Antibodies show distinctions
Analyzing the antibodies in blood samples taken from study participants on the day of their coronavirus test and 28 days later, the researchers ferreted out some notable differences between those who developed severe symptoms and those who didn’t.

One of the key steps in diagnosing or treating many bloodborne diseases is to perform a blood smear, where a drop of blood is spread across a microscope slide for analysis. It is critical the technician collecting the sample perform this smear correctly and consistently, but mistakes at this stage are easy to make and often result in useless samples.
In Review of Scientific Instruments, by AIP Publishing, researchers from Cambridge University, Bath University, and the Ifakara Health Institute developed devices to automate blood smears. Their devices, called autohaem smear and smear+, can consistently create high-quality smears equivalent to those created by human experts.
“Creating blood smears is a laborious, repetitive task that requires an expert level of skill and manual dexterity,” said author Samuel McDermott. “By using automated blood smearing machines, such as autohaem devices, technicians will be able to increase their throughput while maintaining a high enough quality for diagnosis.”
The researchers’ primary focus is on diagnosis of malaria, a deadly disease that kills more than 400,000 people every year. Malaria is best diagnosed by analyzing blood smears through a microscope. While performing research for a previous study, they noticed many of these testing smears were of poor quality.
“In some countries, up to 81.5% of blood smears are prepared incorrectly,” said McDermott. “If a blood smear is prepared incorrectly, when examined under a microscope, the technician will struggle to make a correct diagnosis. Because these smears are often made in a rural clinic and sent to a regional facility for examination, any issues in the smear could cause days of delay.”
Their solution, the autohaem devices, solves this problem by automating the smearing process so every smear is correct and consistent. The devices come in two varieties, the autohaem smear and the autohaem smear+, the latter of which is fully automated with a motorized smearing mechanism. In tests, inexperienced technicians were able to use the device to produce expert-quality smears.
A key goal of the project was to make the autohaem devices accessible to as many people as possible. The researchers designed their devices to be easy to build, using readily available or 3D-printed components. Furthermore, all software and hardware are open-source and freely available.
The next step for the researchers is to test out their design in real-world conditions, thanks to their colleagues at the Ifakara Health Institute in Tanzania.
“They will be able to manufacture and use the devices as part of their research,” said McDermott. “We will be able to use their feedback to improve the design of the device for rural clinics.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Glioblastoma, an aggressive cancer in the brain or spinal cord, has proven stubbornly resistant to newer immunotherapies. And radiation and chemotherapy, the standard treatment for glioblastoma, result in fewer than 10% of patients surviving longer than five years after diagnosis.
But a new study from researchers at Washington University School of Medicine in St. Louis shows that treatment with an immune-boosting protein called interleukin 7 (IL-7) in combination with radiation improves survival in mice with glioblastoma. The new mouse study shows that IL-7 increases the number of T cells in the tumor and other immune organs. Such immune cells can then attack the cancer cells and improve survival.
The findings are published Jan. 14 in Clinical Cancer Research, a journal of the American Association for Cancer Research.
The study in mice suggests promise for a phase 1/2 clinical trial at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis that is investigating a long-acting type of IL-7 in patients with glioblastoma.
Radiation in combination with chemotherapy is the standard of care for various cancers including glioblastoma. Although beneficial against cancer, these treatments also can impair patients’ T cells, known as lymphocytes, that are important for fighting infections. Many glioblastoma patients have low levels of T cells. Glioblastoma patients who have chronically low lymphocyte counts don’t survive as long as patients with higher numbers of these T cells.
“Previously, a multicenter study from the American Brain Tumor Consortium showed a six-month shorter survival for patients with low versus normal numbers of T cells,” said first author Jian L. Campian, MD, PhD, who conducted the research at Washington University School of Medicine and the Brain Tumor Center at Siteman. “We knew that glioblastoma patients with low lymphocytes surprisingly also have low IL-7, which is a growth factor that supports T cells. Normally, people with low T cells should have a high level of IL-7. We wanted to find out if giving IL-7 to patients could increase the numbers of T cells and, in the process, have a positive impact on survival.”
The researchers found that mice with glioblastoma tumors treated with a combination of chemotherapy, radiation and IL-7 lived longer than mice that received only chemotherapy and radiation. On average, control mice that received no treatment lived about 20 days after tumor implantation. The mice that received IL-7 alone lived about 30 days, and those that received radiation alone lived about 35 to 40 days. The mice that received a combination of radiation and IL-7 lived at least 40 days, and many were still alive at 90 days. The longest survival was in the mice that received the triple combination of chemotherapy, radiation and IL-7, most of which lived at least 45 days, with many still alive at the 90-day mark.

Around 1% of the world’s population lives with epilepsy; yet only 65% of epilepsy patients can manage their symptoms with medication. Currently, surgically removing the lesion in the brain responsible for the condition is the only radical cure for epilepsy. Still, many patients have to take medication for the rest of their life to deal with their seizures.
A research group led by professor Ko Matsui from the Super-network Brain Physiology Lab at Tohoku University reported on a stimulation paradigm used on experimental animals that could potentially cultivate resilience to epilepsy.
Frequent seizure-evoking stimulation to the brain has been shown to induce epileptogenesis and epileptic brain conditions. To the researcher’s surprise, however, repeated stimulation resulted in a dramatic decrease in the seizure response to the stimulus.
“Our brain has an infinite ability for plasticity,” says Matsui. “If an epileptic state can be created, we must query whether it is also conceivable to reverse the transition or to override the existing hyper-excitable circuit with an additional suppressive system.”
Using optogenetics technology to control the activity, Dr. Yoshiteru Shimoda, Matsui and their team demonstrated that a specific stimulation paradigm prompted the release of the endogenous inhibitory transmitter adenosine from glial cells. This converted the rat’s brain to a state strongly resistant to seizures.
Details of their findings were published in Neurobiology of Disease online.
Matsui is cautiously optimistic. “Although epileptogenesis unfortunately could not be reversed, we showed we could invoke the homeostatic nature of the brain circuit to contain hyper-excitation.”
For the current study, light-sensitive proteins were genetically expressed in neurons to regulate moderate neuron-to-glial signaling at will. Such optogenetic technology would be difficult to apply in human patients, noted Matsui.
“Despite clinical use being a long way off, it is possible to imagine a future where a therapeutic strategy can directly target glial cells and enable the creation of an epileptic resistant state.”
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Materials provided by Tohoku University. Note: Content may be edited for style and length.

A new study by researchers at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, has identified a new potential pathway for developing therapeutics that target Epstein-Barr virus (EBV). They discovered that the way the EBV genome folds, and thereby expresses itself and causes disease, is more complex than researchers originally thought, and they identified molecules that could be targeted to disrupt this folding.
“We identified two cellular proteins that are important to folding the EBV genome.” said Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program at The Wistar Institute and corresponding author on the paper. “There are existing drugs that target one of these proteins. And our data suggests that if we use that drug on EBV infected cells, we have a way in which we can actually interfere with the folding. That means we can interfere in the way in which the EBV viral genome is functioning.”
EBV, which affects more than 90% of individuals worldwide, is a dynamic virus, meaning that it can change its gene expression. If certain viral genes are expressed, the virus infects B-cells and causes them to overmultiply, which is especially problematic in individuals with suppressed immune systems, such as transplant patients.
Tempera and his colleagues wanted to understand the mechanics behind how the virus manipulates its genetic expression. To do this, they used a modified DNA sequencing technique to examine how the genome folds under different conditions.
“The virus was clever to use the same machinery that regulates the conformation of the human genome to also regulate its own gene expression,” said Tempera. Specifically, the researchers found that EBV uses two proteins, CTFC and PARP1, that also play a role in the expression of the human genome.
PARP1 is already a target of the drug, olaparib (sold under the brand name Lynparza), which is used to treat patients with ovarian cancer. This new study suggests that the drug may have a use for treating EBV positive lymphomas, as well.
“Usually PARP1 is targeted in the context of DNA damage,” said Tempera. “Our paper shows that there is another role of PARP1 in the chromatin folding, so this suggests that maybe we can expand the way in which we can use this drug not only to interfere with DNA damage, but we also might interfere with DNA folding and gene expression, which is something that we are testing now in the lab.”
Co-authors: Sarah M. Morgan, Lisa Beatrice Caruso, Andrew Kossenkov, Sarah Boyle, Paul M. Lieberman, and Italo Tempera from The Wistar Institute; Hideki Tanizawa from University of Oregon; Michael Hulse from Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University; Jozef Madzo and Kelsey Keith from The Coriell Institute for Medical Research; Yinfei Tan from Fox Chase Cancer Center.
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Materials provided by The Wistar Institute. Note: Content may be edited for style and length.

A new study identifies two genes, previously reported to be involved in cancer, as regulators of the metabolic state of the liver. Alterations in these genes influence the likelihood of developing fatty liver disease.
The epidemic of obesity worldwide has increased the risk of accumulating fat in the liver, a preamble to liver inflammation and liver disease. Yet, a still intriguing paradox is the development of fatty liver in lean and normal-weight individuals and in individuals following a healthy diet. Scientists know that two genes, RNF43 and ZNRF3, are mutated in liver cancer patients. However, their role in the development of liver cancer was unknown so far. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, describe now that a loss or mutation of these genes causes an accumulation of lipids and inflammation in the liver in non-obese mice fed a normal diet. These genetic alterations not only increase the accumulation of fat but also the number of liver cells (hepatocytes) in proliferation. In human patients, these alterations also increase the risk of developing NASH and fatty liver and reduce the patient’s survival time. These findings might facilitate the discovery of people at risk and could promote novel therapeutic interventions and better management of the disease.
The liver is our central metabolic organ, which is vital for detoxification and digestion. Chronic liver diseases, such as cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH, inflamed liver), as well as liver cancer, are on the rise worldwide, with a combined mortality of two million individuals dying each year. It is therefore more important than ever to understand their causes and the underlying molecular mechanisms of liver diseases in order to prevent, manage, and treat these increasing patient population subgroups. Previous cancer genomic studies identified RNF43 and ZNRF3, as genes mutated in colon and liver cancer patients. However, their role in liver disease has been unexplored. The research lab of Meritxell Huch at the MPI-CBG, together with colleagues at the Gurdon Institute (Cambridge, UK) and at the University of Cambridge, has now investigated the mechanisms by which alterations in these two genes can affect the emergence of liver diseases. Their study is published in the journal Nature Communications.
To pursue this goal, the researchers worked with mice as an animal model, data from human individuals, human tissues, and liver organoid cultures, which are 3D cellular microstructures made out of hepatocytes that resemble liver in a dish. Germán Belenguer, first author of the study and postdoctoral researcher in the group of Meritxell Huch, explains, “With the organoid, we were able to grow hepatocytes mutated only in these genes, and we saw that the loss of these activates a signal that regulates the metabolism of lipids. As a result, the fat metabolism is no longer under control and lipids accumulate in the liver, which leads in turn to a fatty liver. Another result of the activated signal is that hepatocytes multiply uncontrollably. Both mechanisms combined facilitate the progression towards fatty liver disease and cancer.” The scientists then compared the results from the experiments with patient data in a publicly available dataset from the International Cancer Genome Consortium. They evaluated the prognosis of survival when the two genes are mutated in liver cancer patients and found that patients with these mutated genes show fatty liver disease and have a worse prognosis than liver cancer patients with the two genes unmutated.
“Our findings can help identify individuals with a RNF43/ZNRF3 mutation and therefore at risk of developing a fatty liver or liver cancer,” says Meritxell Huch. She continues, “With the alarming increase in the consumption of fat and sugar worldwide, recognizing those individuals already predisposed because of bearing those genetic mutations might be important for the therapeutic intervention and management of the disease, especially at very early stages or even before the disease is initiated. We will need more studies to further characterize the roles of the two genes in human fatty liver disease, NASH, and human liver cancer and to identify therapeutics that could help those patients that are already intrinsically predisposed to develop the disease.”