Thursday, June 25, 2020
In a new study, a computer algorithm improved the accuracy and efficiency of cervical cancer screening compared with cytology (Pap test), the current standard for follow-up of women who test positive with primary human papillomavirus (HPV) screening. The new approach uses artificial intelligence (AI) to automate dual-stain evaluation and has clear implications for clinical care.
Findings from the study were published June 25, 2020, in the Journal of the National Cancer Institute. The algorithm was developed and the study conducted by investigators at the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with researchers from several other institutions.
“We’re excited to show we have a fully automated approach to cervical cancer screening as a follow-up to a positive HPV test that outperformed the standard method in our study,” said Nicolas Wentzensen, M.D., Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, who led the study. “Based on our results, it could increase the efficiency of cervical cancer screening by finding more precancers and reducing false positives, which has the potential to eliminate a substantial number of unnecessary procedures among HPV-positive women.”
A slide from an automated dual-stain cytology test. The percentages are AI-generated likelihoods of positive results. The image at center (labeled 98.75%) shows a positive result.
Tuesday, June 23, 2020
National Institutes of Health investigators and colleagues have discovered that when the immune system first responds to infectious agents such as viruses or bacteria, a natural brake on the response prevents overactivation. Their new study in mBio describes this brake and the way pathogens such as SARS-CoV-2, the virus that causes COVID-19, turn it on. Their finding provides a potential target for an immunotherapy that might be applied to a wide range of infectious diseases.
When a cell senses an infectious agent with molecules called pathogen recognition receptors, part of its response is to increase cell surface expression of a molecule called CD47, otherwise known as the “don’t eat me” signal. Increased CD47 expression dampens the ability of cells called macrophages, the immune system’s first responders, to engulf infected cells and further stimulate the immune response. Upregulation of CD47 on cells was observed for diverse types of infections including those caused by mouse retroviruses, lymphocytic choriomeningitis virus, LaCrosse virus, SARS CoV-2, and by the bacteria Borrelia burgdorferi and Salmonella enterica typhi.
By blocking CD47-mediated signaling with antibodies in mice infected with lymphocytic choriomeningitis virus, the authors demonstrated they could enhance the speed of pathogen clearance. Furthermore, knocking out the CD47 gene in mice improved their ability to control M. tuberculosis infections and significantly prolonged their survival. In addition, retrospective studies of cells and plasma from people infected with hepatitis C virus indicated that humans also upregulate CD47. In these studies, inflammatory cytokine stimuli and direct infection both promoted increased CD47 expression.
Colorized scanning electron micrograph of a cell (purple) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample.
Thursday, June 11, 2020
A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, identified genomic features of SARS-CoV-2, the virus that causes COVID-19, and other high-fatality coronaviruses that distinguish them from other members of the coronavirus family. This research could be a crucial step in helping scientists develop approaches to predict, by genome analysis alone, the severity of future coronavirus disease outbreaks and detect animal coronaviruses that have the potential to infect humans. The findings were published this week in the Proceedings of the National Academy of Sciences.
COVID-19, an unprecedented public health emergency, has now claimed more than 380,000 lives worldwide. This crisis prompts an urgent need to understand the evolutionary history and genomic features that contribute to the rampant spread of SARS-CoV-2.
“In this work, we set out to identify genomic features unique to those coronaviruses that cause severe disease in humans,” said Dr. Eugene Koonin, an NIH Distinguished Investigator in the intramural research program of NLM’s National Center for Biotechnology Information, and the lead author of the study. “We were able to identify several features that are not found in less virulent coronaviruses and that could be relevant for pathogenicity in humans. The actual demonstration of the relevance of these findings will come from direct experiments that are currently getting under way.”
The full genomes of all human coronaviruses were aligned to identify regions (red) that might code for lethal differences in the virus that causes COVID-19 as well as SARS and MERS. These differences could be targets for testing or treatments.
Thursday, June 11, 2020
Scientists have developed a new test that can help identify people who are likely to develop hepatocellular carcinoma (HCC), the most common form of liver cancer. The approach uses a simple blood test to check for the patient’s previous exposure to certain viruses.
A study of the new approach was led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The study also involved researchers from the National Institute of Diabetes and Digestive and Kidney Diseases and several academic centers. The findings were published June 10 in Cell.
“Together with existing screening tests, the new test could play an important role in screening people who are at risk for developing HCC. It could help doctors find and treat HCC early. The method is relatively simple and inexpensive, and it only requires a small blood sample,” said the study’s leader, Xin Wei Wang, Ph.D., co-leader of the NCI Center for Cancer Research (CCR) Liver Cancer Program.
The blood test looks at past viral infections and can distinguish people who are likely to develop liver cancer from those with chronic liver disease and healthy livers. Image credit: Jinping Liu, Ph.D., University of Pennsylvania
Thursday, June 11, 2020
Woychik will lead NIH’s research efforts on environmental influences on human health and also serve as director of the U.S. National Toxicology Program
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has appointed Richard (Rick) P. Woychik, Ph.D., as director of NIH’s National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina. Dr. Woychik served as acting director of the NIEHS since October 2019 and officially began his new role as the NIEHS director on June 7, 2020. NIEHS conducts and supports environmental health sciences in alignment with real-world public health needs and translates scientific findings into knowledge that can inform real-life individual and public health outcomes.
“Innovation has been a hallmark of Rick’s scientific career and it’s at the center of his vision for leading NIEHS,” said Dr. Collins. “He will be working to support new technologies and scientific approaches throughout the field of environmental health sciences — applying his proven skills in scientific excellence, creativity, and rigor to improving public health.”
Woychik is highly respected for a long list of accomplishments in mammalian genetics and environmental epigenetics. His laboratory was the first to identify a gene associated with polycystic kidney disease, the first to connect a protocadherin gene ultimately linked to hearing loss in Cushing’s disease patients, and the first to clone an obesity-related gene called agouti. Dr. Woychik says his passion for epigenetics and environmental health sciences started when his research group discovered that the obesity trait associated with one of the agouti mutant mouse lines was influenced by the epigenome during embryonic development.
Dr. Rick Woychik has been named Director of NIEHS.
Monday, June 8, 2020
Study shows mutations in inflammation-related genes are associated with PFAPA syndrome
Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, have discovered clues to the possible cause of recurring, non-contagious fevers and sores that affect only children. Several genes have been implicated with the syndrome, known as PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis), which could lead to new treatments. The results were published in the journal PNAS this week.
The findings were made possible by the realization of commonalities with other chronic inflammatory conditions that also involved sores on the body, including the common canker sore. The study illustrates how long-standing health mysteries may now be solved when researchers discover new biological connections with the help of increasing amounts of genomic data.
In 1987, researchers first described a syndrome seen in 12 children, which was marked by recurrent fever, painful canker sores, sore throat and inflamed lymph nodes. The condition starts at an early age, between the ages of 1 and 5. The first sign is fever, accompanied by sore throat with redness and other symptoms.
“PFAPA syndrome is the most periodic of periodic fevers, with many children having an episode every month lasting three to five days,” said Kalpana Manthiram, M.D., Clinical Fellow at NHGRI and lead author of the study. “That is an immense burden on families since these kids cannot go to school and may be bedridden for days during flares.”
Friday, June 5, 2020
Researchers at the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, have identified a specific, front-line defense that limits the infection to the olfactory bulb and protects the neurons of the olfactory bulb from damage due to the infection. Neurons in the nose respond to inhaled odors and send this information to a region of the brain referred to as the olfactory bulb. Although the location of nasal neurons and their exposure to the outside environment make them an easy target for infection by airborne viruses, viral respiratory infections rarely make their way from the olfactory bulb to the rest of the brain, where they could cause potentially fatal encephalitis. The study was published in Science Immunology.
Taking advantage of special viruses that can be tracked with fluorescent microscopy, the researchers led by Dorian McGavern, Ph.D., senior investigator at NINDS, found that a viral infection that started in the nose was halted right before it could spread from the olfactory bulb to the rest of the central nervous system.
“Airborne viruses challenge our immune system all the time, but rarely do we see viral infections leading to neurological conditions,” said Dr. McGavern. “This means that the immune system within this area has to be remarkably good at protecting the brain.”
When virus (labeled in green) enters the nasal passages, its spread is abruptly halted just before entering the CNS (blue oval structures at the top of the image).
Friday, June 5, 2020
Early data from a clinical study suggest that blocking the Bruton tyrosine kinase (BTK) protein provided clinical benefit to a small group of patients with severe COVID-19. Researchers observed that the off-label use of the cancer drug acalabrutinib, a BTK inhibitor that is approved to treat several blood cancers, was associated with reduced respiratory distress and a reduction in the overactive immune response in most of the treated patients.
The findings were published June 5, 2020, in Science Immunology. The study was led by researchers in the Center for Cancer Research at the National Cancer Institute (NCI), in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), both part of the National Institutes of Health, as well as the U.S. Department of Defense’s Walter Reed National Military Medical Center, and four other hospitals nationally.
These findings should not be considered clinical advice but are being shared to assist the public health response to COVID-19. While BTK inhibitors are approved to treat certain cancers, they are not approved as a treatment for COVID-19. This strategy must be tested in a randomized, controlled clinical trial in order to understand the best and safest treatment options for patients with severe COVID-19.
Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample.
Thursday, May 28, 2020
Data offers valuable resource for developing stem cell-based therapies for hearing loss
A team of researchers has generated a developmental map of a key sound-sensing structure in the mouse inner ear. Scientists at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health, and their collaborators analyzed data from 30,000 cells from mouse cochlea, the snail-shaped structure of the inner ear. The results provide insights into the genetic programs that drive the formation of cells important for detecting sounds. The study also sheds light specifically on the underlying cause of hearing loss linked to Ehlers-Danlos syndrome and Loeys-Dietz syndrome.
The study data is shared on a unique platform open to any researcher, creating an unprecedented resource that could catalyze future research on hearing loss. Led by Matthew W. Kelley, Ph.D., chief of the Section on Developmental Neuroscience at the NIDCD, the study appeared online in Nature Communications. The research team includes investigators at the University of Maryland School of Medicine, Baltimore; Decibel Therapeutics, Boston; and King’s College London.
“Unlike many other types of cells in the body, the sensory cells that enable us to hear do not have the capacity to regenerate when they become damaged or diseased,” said NIDCD Director Debara L. Tucci, M.D., who is also an otolaryngology-head and neck surgeon. “By clarifying our understanding of how these cells are formed in the developing inner ear, this work is an important asset for scientists working on stem cell-based therapeutics that may treat or reverse some forms of inner ear hearing loss.”
Single-cell RNA sequencing helped scientists map how sensory hair cells (pink) develop in a newborn mouse cochlea.
Wednesday, May 27, 2020
Molecules released into the blood following mild traumatic brain injury (TBI) may be indicators of neuronal damage associated with conditions such as post-traumatic stress disorder (PTSD) and depression, researchers from the National Institute of Nursing Research (NINR), part of the National Institutes of Health, have found. This study included military veterans and servicemembers who were enrolled in the Chronic Effects of Neurotrauma Consortium (CENC) multicenter observational study of the long-term effects of mild TBI and is published in Neurology.
“This study brings us closer to identifying biomarkers to predict risk for PTSD, depression, and similar conditions in military personnel and others who have experienced a traumatic brain injury,” said Jessica Gill, Ph.D., R.N., F.A.A.N., deputy scientific director, and acting deputy director, NINR, and chief of NINR’s Tissue Injury Branch, who conducted the study with colleagues.
The researchers analyzed blood samples from former military personnel who had experienced one to two TBIs, more than two TBIs, or no TBIs. They screened for molecules released directly into the blood by cells of damaged tissue or inside vesicles called exosomes — bubble-like structures that contain a representative sample of cellular molecules. There was a significant correlation between multiple mild TBIs across the lifespan and higher levels of neurofilament light (NfL), a structural protein found inside neurons, and molecules involved in inflammation, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6).