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Tag: Johns Hopkins Medicine

  • Scientists Pinpoint Growth of Brain’s Cerebellum as Key to Evolution of Bird Flight

    Scientists Pinpoint Growth of Brain’s Cerebellum as Key to Evolution of Bird Flight


    **EMBARGOED UNTIL 7:01 P.M. ET TUESDAY, JAN 30**

    Evolutionary biologists at Johns Hopkins Medicine report they have combined PET scans of modern pigeons along with studies of dinosaur fossils to help answer an enduring question in biology: How did the brains of birds evolve to enable them to fly?

    The answer, they say, appears to be an adaptive increase in the size of the cerebellum in some fossil vertebrates. The cerebellum is a brain region responsible for movement and motor control.

    The research findings are published in the Jan. 31 issue of the Proceedings of the Royal Society B.

    Scientists have long thought that the cerebellum should be important in bird flight, but they lacked direct evidence. To pinpoint its value, the new research combined modern PET scan imaging data of ordinary pigeons with the fossil record, examining brain regions of birds during flight and braincases of ancient dinosaurs.

    “Powered flight among vertebrates is a rare event in evolutionary history,” says Amy Balanoff, Ph.D., assistant professor of functional anatomy and evolution at the Johns Hopkins University School of Medicine and first author on the published research.

    In fact, Balanoff says, just three groups of vertebrates, or animals with a backbone, evolved to fly: extinct pterosaurs, the terrors of the sky during the Mesozoic period, which ended over 65 million years ago, bats and birds.

    The three species are not closely related on the evolutionary tree, and the key factors or factor that enabled flight in all three have remained unclear.

    Besides the outward physical adaptations for flight, such as long upper limbs, certain kinds of feathers, a streamlined body and other features, Balanoff and her colleagues designed research to find features that created a flight-ready brain.

    To do so, she worked with biomedical engineers at Stony Brook University in New York to compare the brain activity of modern pigeons before and after flight.

    The researchers performed positron emission tomography, or PET, imaging scans, the same technology commonly used on humans, to compare activity in 26 regions of the brain when the bird was at rest and immediately after it flew for 10 minutes from one perch to another. They scanned eight birds on different days.

    PET scans use a compound similar to glucose that can be tracked to where it’s most absorbed by brain cells, indicating increased use of energy and thus activity. The tracker degrades and gets excreted from the body within a day or two.

    Of the 26 regions, one area — the cerebellum — had statistically significant increases in activity levels between resting and flying in all eight birds. Overall, the level of activity increase in the cerebellum differed by more than two standard statistical deviations, compared with other areas of the brain.

    The researchers also detected increased brain activity in the so-called optic flow pathways, a network of brain cells that connect the retina in the eye to the cerebellum. These pathways process movement across the visual field.

    Balanoff says their findings of activity increase in the cerebellum and optic flow pathways weren’t necessarily surprising, since the areas have been hypothesized to play a role in flight.

    What was new in their research was linking the cerebellum findings of flight-enabled brains in modern birds to the fossil record that showed how the brains of birdlike dinosaurs began to develop brain conditions for powered flight.

    To do so, Balanoff used a digitized database of endocasts, or molds of the internal space of dinosaur skulls, which when filled, resemble the brain.

    Balanoff identified and traced a sizable increase in cerebellum volume to some of the earliest species of maniraptoran dinosaurs, which preceded the first appearances of powered flight among ancient bird relatives, including Archaeopteryx, a winged dinosaur.

    Balanoff and her team also found evidence in the endocasts of an increase in tissue folding in the cerebellum of early maniraptorans, an indication of increasing brain complexity.

    The researchers cautioned that these are early findings, and brain activity changes during powered flight could also occur during other behaviors, such as gliding. They also note that their tests involved straightforward flying, without obstacles and with an easy flightpath, and other brain regions may be more active during complex flight maneuvers.

    The research team plans next to pinpoint precise areas in the cerebellum that enable a flight-ready brain and the neural connections between these structures.

    Scientific theories for why the brain gets bigger throughout evolutionary history include the need to traverse new and different landscapes, setting the stage for flight and other locomotive styles, says Gabriel Bever, Ph.D., associate professor of functional anatomy and evolution at the Johns Hopkins University School of Medicine.

    “At Johns Hopkins, the biomedical community has a wide-ranging set of tools and technology to help us understand evolutionary history and link our findings to fundamental research on how the brain works,” he adds.

    In addition to Balanoff and Bever, other authors of the study are Elizabeth Ferrer of the American Museum of Natural History and Samuel Merritt University; Lemise Saleh and Paul Vaska of Stony Brook University; Paul Gignac of the American Museum of Natural History and University of Arizona, M. Eugenia Gold of the American Museum of Natural History and Suffolk University; Jesús Marugán-Lobón  of the Autonomous University of Madrid; Mark Norell of the American Museum of Natural History; David Ouellette of Weill Cornell Medical College; Michael Salerno of the University of Pennsylvania; Akinobu Watanabe of the American Museum of Natural History, New York Institute of Technology College of Osteopathic Medicine, and Natural History Museum of London; and Shouyi Wei of the New York Proton Center.

    Funding for the research was provided by the National Science Foundation.





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  • Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

    Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

    **EMBARGOED UNTIL 8 P.M. ET SATURDAY, NOV. 4**

    Newswise — A new pathologic scoring system that accurately assesses how much lung tumor is left after a patient receives presurgical cancer treatments can be used to predict survival, according to new research led by investigators at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center and the Mark Foundation Center for Advanced Genomics and Imaging at the Johns Hopkins University.

    The study shows that pathologic assessment of residual viable tumor (RVT) in patients treated with immunotherapy and chemotherapy before lung cancer surgery provides a robust and efficient evaluation of patient treatment response that may be useful to guide patient therapy and predict survival. This latter finding supports pathologic evaluation of tumors as an early clinical trial endpoint and a surrogate of survival for potential accelerated regulatory approvals.

    The results were published on Nov. 4 in the journal Nature Medicine and simultaneously presented by senior study author Janis Taube, M.D., M.Sc., director of the Division of Dermatopathology at the Johns Hopkins University School of Medicine and a member of the Kimmel Cancer Center, at the Society for Immunotherapy of Cancer annual meeting in San Diego.

    Immunotherapies harness a patient’s immune system to target their tumors. These powerful drugs are often paired with conventional chemotherapies to help shrink a patient’s tumors before surgery, increasing the likelihood of successfully eliminating the cancer. To gauge treatment success, oncologists typically rely on radiologic imaging of the remaining tumor, but the results aren’t always as accurate in early-stage tumors as they are for more advanced cancers. More recently, circulating tumor DNA (ctDNA) clearance, which uses genetic sequencing to detect lung cancer-associated mutations in patient blood samples, has also shown promise, but is not yet widely available.

    For the new study, investigators performed a new analysis on data from the randomized, phase 3 CheckMate 816 study. That study found that treating presurgical non-small cell lung cancer patients with immunotherapy (nivolumab) plus chemotherapy improved event-free survival. This important surrogate endpoint can help predict long-term survival and pathologic complete response, which measures whether any tumor is left.

    “Most studies have focused on whether you have no tumor left or less than or equal to 10% of the tumor left, which is called a major pathologic response,” says lead study author Julie Stein Deutsch, M.D., an assistant professor of dermatology at Johns Hopkins.

    During the study, the investigators used a new approach, which measures residual tumor in patients who received neoadjuvant therapy, to predict outcomes in patients with a greater range of treatment responses. They used immune-related pathologic response criteria (irPRC) to look for pathologic changes that indicated the tumor had been present in the tissue before immunotherapy but was destroyed by the treatment, allowing them to measure what percentage of the tumor was left, or the RVT, ranging from 0% to 100%.

    As a result, they were able to separate patients into three groups based on how much tumor was left. In the future, data such as these may help guide the next round of clinical trials and ultimately help oncologists decide how to treat individuals in these subgroups, Deutsch says. For example, patients with no tumor left may be able to skip postsurgical immunotherapy or have a relatively limited amount, while individuals in the intermediate group may need to continue immunotherapy for longer. Those who showed a very limited response may need to switch to a new therapy or add a new therapy to their regimen. The team’s next steps will include identifying the most clinically meaningful cutoffs for RVT.

    They also looked beyond the primary tumor and used RVT to assess the immunotherapy effect on tumor in the lymph nodes, which showed additive value with the primary tumor for predicting survival. Long term, it may also be possible to strategically combine pathology, radiology and ctDNA results for the longitudinal monitoring of treatment efficacy.

    Already, the investigators demonstrated the pathologic scoring system can assess 10 types of tumors, including lung, skin and colorectal cancers, which could be another advantage over other tumor scoring systems.

    “The common features seen across these multiple tumor types means that pathologists don’t have to switch to different scoring systems for assessing pathologic response. This is similar to what already exists in radiology, where the RECIST system is used across all tumor types for determining objective response to therapy,” Taube says, noting that pathologists already are completing the necessary workflows as part of standard procedures when assessing surgically removed tumors. Assessing RVT is inexpensive and uses tools and supplies commonly used by pathologists, Deutsch says, which may also make it accessible for those working in low-resource settings.

    “It is important that as these immunotherapies move into clinical trials and become standard of care, pathologists worldwide have a standard scoring system for the assessment of treatment response,” Taube says. 

    Study co-authors were Ashley Cimino-Mathews, Elizabeth Thompson, Patrick M. Forde, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ludmila Danilova and Joel Sunshine of Johns Hopkins. Other authors were from the Hospital Universitario Puerta de Hierro in Madrid, Spain; McGill University Health Center in Montreal, Canada; Institut du Thorax Curie-Montsouris in Paris, France; Aberdeen Royal Infirmary in the United Kingdom; Bristol Myers Squibb in Princeton, New Jersey; and Queen’s University in Kingston, Canada.

    The study was supported by Bristol Myers Squibb, Ono Pharmaceutical Company Ltd., the Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Mark Foundation for Cancer Research and the National Institutes of Health (grant R01 CA142779).

    Deutsch is named on a patent for system and method for annotating pathology images to predict patient outcome (U.S. Provisional Patent Application 63/313,548, filed in Feb. 2022). Taube receives support for this study from Bristol Myers Squibb; receives consulting fees from AstraZeneca, Bristol Myers Squibb, Merck and Roche; participates on advisory boards from AstraZeneca; and is named on a patent for a machine learning algorithm for irPRC. These relationships are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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  • Newsmakers: Basic Research Findings by Johns Hopkins Scientists Focus on Gene Sequencing, Hearing Loss and a Brain Disorder

    Newsmakers: Basic Research Findings by Johns Hopkins Scientists Focus on Gene Sequencing, Hearing Loss and a Brain Disorder

    Newswise — Yes, Scientists Have Sequenced the Entire Human Genome, But They’re Not Done Yet

    The human genome, from end to end, has been sequenced, meaning scientists worldwide have identified most of the nearly 20,000 protein-coding genes. However, an international group of scientists notes there’s more work to be done. The scientists point out that even though we have nearly converged on the identities of the 20,000 genes, the genes can be cut and spliced to create approximately 100,000 proteins, and gene experts are far from agreement on what those 100,000 proteins are.

    The group, which convened last fall at Cold Spring Harbor Laboratory in New York, has now published a guide for prioritizing the next steps in the effort to complete the human gene “catalog.”

    “Many scientists have been working on efforts to fully understand the human genome, and it’s much more difficult and complex than we thought,” says Steven Salzberg, Ph.D., Bloomberg Distinguished Professor of Biomedical Engineering, Computer Science, and Biostatistics at The Johns Hopkins University. “We have provided a state of the human gene catalog and a guide on what’s needed to complete it.”

    Salzberg, along with Johns Hopkins biomedical engineer and associate professor Mihaela Pertea, Ph.D., M.S., M.S.E., postdoctoral researcher Ales Varabyou and 19 other scientists, offered perspectives on the human gene catalog Oct. 4 in the journal Nature.

    The scientists say that while the final list of protein coding genes is nearly complete, scientists have not yet fully cataloged the variety of ways that a gene can be cut, or spliced, resulting in “isoforms” of proteins that are slightly different. Some protein isoforms will not affect the protein’s function but some may be different enough to result in increased risk for a particular trait, condition or illness.

    To complete the catalog, the scientists propose a comprehensive look at how each gene is expressed into functional and nonfunctional proteins and the three-dimensional shape of those proteins.

    The scientists also propose a focus on cataloging non-coding RNA genes. RNA is the genetic material that is transcribed by DNA and follows a molecular path to making proteins. Instead of proteins, non-coding RNA genes encode other types of molecular material that performs a cellular function.

    Finally, the international group emphasizes the importance of enhancing commonly used databases of gene variations that cause illness and disease, improving clinical laboratory standards for annotating DNA sequencing results and developing new technology to enable more effective and precise methods to match the wide array of proteins with their gene products.

    When It Comes to Hearing, the Left and Right Sides of the Brain Work Together, Mouse Research Shows

    Johns Hopkins-led research has revealed an extensive network of connections between the right and left sides of the brain when mice are exposed to different sounds. The researchers also found that some areas of the brain are specialized to recognize certain sounds, such as “calls” from the animals. Further, the researchers also found that deaf mice had far fewer right and left brain connections, suggesting that the brain needs to “hear” and process sound during early ages to spur development of left-right brain connections.

    The findings, say the researchers, may eventually help scientists pinpoint the time period when such brain connections and specialization form, and offer potential insights into how to restore hearing loss.

    “The auditory system is a collection of parts, which need to be connected properly,” says Johns Hopkins neuroengineer Patrick Kanold, Ph.D., a professor of biomedical engineering. “Using a novel microscope that enabled us to see both brain hemispheres at the same time, we found that some of those connections are between the right and left brain hemispheres, allowing functional specialization. When the brain does not get the right inputs, for example in hearing loss, these brain connections are missing. This obviously is an issue if we hope to restore hearing at a later age.”

    In efforts to find new ways to restore hearing, Kanold’s team will continue its work to identify the specific time period when brain connections form in response to sound and how to restore abnormal connections. The team is also continuing research to understand how the brain adapts to and modulates sound processing to filter out distracting signals, such as its recent work indicating that the brain’s frontal cortex provides specific signals to the auditory system during behaviors that might help in this filtering process.

    New Mouse Models May Help Scientists Find Therapies for Brain Development Disorder

    For more than 25 years, Richard Huganir, Ph.D., Bloomberg Distinguished Professor of Neuroscience and Psychological and Brain Sciences and director of the Solomon H. Snyder Department of Neuroscience, at the Johns Hopkins University School of Medicine, has studied the protein SYNGAP1 that is now known to be linked to a group of neurodevelopmental disorders that are usually diagnosed during early childhood. Working with biotechnology companies to find new therapies for the conditions, his team at Johns Hopkins Medicine reports it has developed new mouse models that more accurately represent genetic mutations in people who have SYNGAP1-related disorders.

    The new collection of mouse models, now available to scientists developing treatments, have several variations in the SYNGAP1 gene, which were discovered to cause conditions marked by seizures, cognitive impairment, social deficits and sleep disturbances.

    The SYNGAP1 gene, found also in humans, makes proteins that regulate synapses, the space between two neurons where they trade chemical and molecular messages. When SYNGAP1 is mutated, as in the case of SYNGAP1-related disorders in people, neurons make less of the protein in the synapse, and learning and memory are impaired.

    In other mouse models, called “knock-out” models, the SYNGAP1 gene is removed entirely. Huganir says both the knock-out models and the new versions — “knock-in” models, which carry a variety of SYNGAP1 mutations linked to the disorders — will be helpful in finding therapies that boost SYNGAP1 protein production.

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  • Donlin Long, First Head of Johns Hopkins Medicine’s Neurosurgery Department and Pain Treatment Pioneer, Dies at 89

    Donlin Long, First Head of Johns Hopkins Medicine’s Neurosurgery Department and Pain Treatment Pioneer, Dies at 89

    Newswise — Donlin M. Long, founding chair of the Johns Hopkins University School of Medicine’s Department of Neurosurgery and a pioneer in the treatment of chronic pain, died Sept. 19. He was 89.

    Highly regarded for his neurosurgical skills, extensive impact on pain reduction research and neurological studies and mentorship of medical students, residents and fellows, Long is credited with establishing the Department of Neurosurgery at Johns Hopkins in 1973, which until then had been a division of the Department of Surgery.

    “Don Long was a true renaissance man and an innovative, master neurosurgeon who nurtured generations of neurosurgical leaders who have transformed our field,” said Henry Brem, M.D., the Harvey Cushing Professor of Neurosurgery and Director of the Department of Neurosurgery at the Johns Hopkins University School of Medicine. “Dr. Long was compassionate and a great role model.”

    When Long joined Johns Hopkins, he organized, what were called at the time, “centers of expertise,” providing patients with one-stop access to specialists in neurology, neurosurgery, orthopaedics and other specialties.

    Long also popularized the concept of competency-based training for neurosurgeons. By the time he stepped down as department director in August of 2000, the full-time neurosurgical faculty had more than doubled, the surgical caseload had increased substantially, rising to some 3,500 annually at The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, seven centers of expertise had been created, bringing together experts on everything from chronic pain and vascular diseases to skull base surgery and spinal diseases, and research funding had grown exponentially to $5.5 million a year.

    Descended from New England Quakers, Long was born on April 14, 1934, in Rolla, Missouri. His father was a chemist for the state health department and his mother was a schoolteacher. The family soon moved to Jefferson City. He obtained his undergraduate degree in 1955 and his medical degree in 1959 from the University of Missouri.

    As an intern at the University of Minnesota, Long originally planned to become a cardiac surgeon, but changed to neurosurgery after watching pioneer neurosurgeon Lyle French operate.

    As a resident at Minnesota, Long and fellow resident Joseph Galicich did the research that led to the now-universal use of steroids to reduce postoperative brain swelling. While earning his 1964 doctorate in neuroanatomy, he also did landmark research on the biological structure of the blood vessels in the brain.

    Using a then-new device, the electron microscope, he was able to make the first photographs of the cells that form the inner lining of the brain’s blood vessels, providing images that revealed why brain swelling led to a breakdown of what is known as the blood/brain barrier. This is a special system of cells that form the lining of the brain’s tiniest blood vessels and separate the brain from the central nervous system, protecting it from harmful substances in the bloodstream.

    Once he came to Johns Hopkins, Long continued his groundbreaking research into chronic pain, where he designed the first external transcutaneous electrical nerve stimulator — now universally known simply as TENS — for stimulating peripheral nerves to ease pain.

    In 1981, he and Johns Hopkins colleagues announced the invention of the first battery-powered, rechargeable, implantable electronic stimulator. It became a standard tool in pain management around the world.

    In addition, Long collaborated with colleagues at the Johns Hopkins Applied Physics Laboratory to invent an implantable medication pump, now a standard device used for the administration of insulin in the treatment of patients with diabetes.

    Long is survived by his wife of 64 years, Harriett Page Long; three children, Dr. Kimberley Page Riley and her spouse Dr. Lee Hunter Riley, III, Elisabeth Merchant Long, and David Bradford Long and his spouse Dr. Elizabeth Selvin; and four grandchildren, Lauren Palmer Riley, Thomas Hunter Riley, Benjamin Logan Selvin Long and Eli Duncan Selvin Long.

    Read the full obituary for Donlin M. Long at the Johns Hopkins Department of Neurosurgery website: In Memoriam: Donlin M. Long | Johns Hopkins Neurology and Neurosurgery

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  • T. Boone Pickens Foundation Donates $20 Million to Wilmer Eye Institute, Johns Hopkins Medicine

    T. Boone Pickens Foundation Donates $20 Million to Wilmer Eye Institute, Johns Hopkins Medicine

    Newswise — The T. Boone Pickens Foundation, established by the late, Texan innovative energy leader and philanthropist, is donating $20 million to the Wilmer Eye Institute, Johns Hopkins Medicine. The gift, announced in 2013, is one of the largest research donations in Wilmer’s history. It will fund vision-saving research and a professorship.

    Pickens’ interest in the treatment and research of eye conditions developed in the 1980s after his father’s diagnosis of macular degeneration, a progressive condition that disrupts the central field of vision and causes vision loss. At the time, no treatments existed to prevent decline of his father’s healthy vision.

    Pickens later publicly disclosed his own battle with macular degeneration and sought treatment from Wilmer for both this condition and cataracts. His care team, which included Walter Stark, M.D., and Neil Bressler, M.D., and which used the latest and most advanced treatments, was able to help Pickens retain most of his eyesight until his death in 2019 at the age of 91.

    “Walter Stark, like my dad, had deep Oklahoma roots,” says Pickens’ daughter, Liz Cordia. “They became fast friends. This friendship ultimately evolved into Walter treating my grandad’s glaucoma and my dad’s cataracts and later diagnosing his macular degeneration.”

    In 2005 and 2009, Pickens made gifts totaling $8 million — first to establish the Boone Pickens Professorship of Ophthalmology, currently held by Amir Kashani, M.D., Ph.D., and then to help with construction of the Robert H. and Clarice Smith Building to house Wilmer’s research laboratories and state of the art operating rooms.

    “Mr. Pickens’ generous contributions to Wilmer will serve as the foundation on which teams of clinicians, scientists and engineers will develop novel diagnostic and therapeutic interventions to prevent blindness and improve the health of people around the world,” says Kashani.

    Along with cutting-edge research and the Boone Pickens Professorship, the $20 million gift from the Pickens Foundation will endow additional Boone Pickens Professorships, specifically for young investigators, called Rising Professorships. The funds will be allocated to researchers who conduct novel, vision-saving research that may be overlooked by other potential funding opportunities.

    ”The Pickens Rising Professors will be our best and brightest physician-scientists who are early in their careers and exploring their new ideas for improving the care of patients and ending blinding eye diseases” says Peter McDonnell, M.D., Wilmer’s director. “This transformative gift from our friend, Mr. Pickens, will accelerate our work in artificial intelligence, stem cells, nanotechnology and other exciting new frontiers.”

    The gift comes after Cordia and Jay Rosser, a foundation representative, visited Wilmer leaders and researchers early this summer to discuss how the donation would be used at the institute and new research spaces under construction at Johns Hopkins.

    “Advancing health and medical initiatives that would have impacts spanning generations was a core objective in Boone’s giving,” says Rosser. “When all is said and done, his philanthropic impact exceeded $1 billion and was directed at some of the world’s most cutting-edge research institutions, and the Wilmer Eye Institute stands high on that list.”

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  • Transcription Factors Contribute to Subtypes of Colorectal Cancers

    Transcription Factors Contribute to Subtypes of Colorectal Cancers

    Newswise — New research in colorectal cancers directed by investigators at the Johns Hopkins Kimmel Cancer Center suggests that expression of transcription factors — proteins that help turn specific genes on or off by binding to nearby DNA — may play a central role in the degree of DNA methylation across the genome, contributing to the development of different subtypes of these cancers. Methylation is a process in which certain chemical groups attach to areas of DNA that guide genes’ on/off switches. Studying the expression of these transcription factors in patients with colorectal cancers could reveal biomarkers to help determine overall survival in people with a subgroup of colorectal cancers who generally have better survival rates and, importantly, respond better to immune checkpoint therapy — a type of immunotherapy that releases restraints that cancer cells place on the immune response — and other treatments. Similar patterns of transcription factor expression could be seen by the researchers even in precancerous polyps, and could potentially be used by physicians to determine which patients need closer follow-up to prevent cancer development.

    A description of the work was published online July 24 in the journal Proceedings of the National Academy of Sciences.

    Aberrant DNA methylation is a well-known phenomenon occurring in cancers, explains senior study author Hariharan Easwaran, Ph.D., M.Sc., an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, but the degree of DNA methylation varies in cancers of the same tissue type. Some colon and other cancers have a very high degree of DNA methylation gains while others have much lower frequency of DNA methylation gains, he says. Traditionally, these have been described in an area of the genome known as a promoter region, which helps launch the transcription process. The exact mechanisms underlying these changes have not been clear.

    In a series of laboratory studies of genetic material taken from tubular adenomas (precancerous polyps in the colon) and colon tumors, the researchers linked cancer-specific transcription factor expression alterations to methylation alterations in colorectal cancers and their premalignant precursor lesions, which provided insights into the origins and evolution of different molecular subtypes of colorectal cancers.

    Specifically, researchers observed that some regions of the genome undergoing increased methylation tend to have binding sites for transcription factors that are downregulated, or have low expression. In some types of colon cancer, based on the types of genetic alterations associated with the cancer, transcription factors are upregulated or have higher expression.

    The findings suggest that cancer-specific methylation differences potentially evolve due to perturbation in the activity or expression of transcription factors. Similar changes in DNA methylation patterns were observed in precancerous polyps.

    “These studies highlight that the transcription factor expression changes and corresponding DNA methylation changes are early events during tumor development,” says lead study author Yuba Bhandari, Ph.D., a research associate at the Johns Hopkins Kimmel Cancer Center. “As polyps do not carry all of the key genetic changes typically found in full-blown cancer cells, the transcription factor changes may represent the earliest molecular regulators of precancerous cells, with profound impact on the genome-wide DNA methylation changes.”

    The specific set of transcription factors identified in the study may help in stratifying colorectal cancer prognosis, Easwaran adds.

    “This is particularly important, because multiple studies have shown that a certain subtype of colorectal cancers responds best to immune checkpoint blockade therapies, while others may not fare as well,” he says. “Expression profiling of relevant transcription factors may help develop better therapeutic strategies across subtypes of colorectal cancers.”

    Additional study co-authors included Rachael Powers, Sehej Parmar, Sara-Jayne Thursby, Ekta Gupta, Ozlem Kulak, Kurtis Bachman and Stephen Baylin of Johns Hopkins. Additional investigators from Janssen Research and Development in Pennsylvania and in Belgium contributed.

    The work was supported by the National Institutes of Health grants R01CA230995 and R01CA229240; National Institute of Environmental Health Sciences grant R01ES011858; National Cancer Institute grant R21CA212495; Sam Waxman Research Foundation and National Institute on Aging grant U01AG066101; Janssen Initiative; Commonwealth Grant; and Grollman Glick Scholarship.

    Baylin consults for MDxHealth. Methylation-specific PCR is licensed to MDxHealth in agreement with The Johns Hopkins University. Baylin and JHU are entitled to royalty shares received from sales. These arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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  • Martin/Hopkins Method to Calculate LDL Or ‘Bad’ Cholesterol Outperforms Other Equations, Study Shows

    Martin/Hopkins Method to Calculate LDL Or ‘Bad’ Cholesterol Outperforms Other Equations, Study Shows

    Newswise — In a new large, comprehensive analysis that looked at data from more than 5 million patients, the Martin/Hopkins method developed by Johns Hopkins researchers to calculate low-density lipoprotein (LDL) cholesterol — so-called bad cholesterol — produces higher accuracy rates than the nearly two dozen other available equations.

    The findings, published June 19 in Global Heart, reveal that overall, the Martin/Hopkins algorithm correctly classified 89.6% of patients’ LDL cholesterol values, followed by the Sampson method (which was proposed by the National Institutes of Health), which correctly classified 86.3%. The previous gold standard of testing LDL cholesterol levels, the Friedewald method, correctly classified 83.2% of patients. An even larger advantage of the Martin/Hopkins algorithm was seen over other methods for patients with characteristics such low cholesterol and high triglyceride levels.

    For the study, researchers looked at data from October 2015 to June 2019, using the Very Large Database of Lipids — a cohort made up of 5,051,467 adult and pediatric patients. The average age was 56, and 53.3% were women. Analyzing 23 identified LDL cholesterol equations, the researchers found that following the Martin/Hopkins equation, those with the most accurate findings were Sampson, Chen (84.4%), Puavilai (84.1%), Delong (83.3%) and Friedewald. The other 17 equations were less accurate than Friedewald, with accuracy as low as 35.1%.

    Assessing LDL cholesterol is important for understanding the risk of stroke and heart disease, which is the #1 cause of death globally. High levels of LDL cholesterol are associated with buildup of plaque in the arteries that can narrow the blood vessels and restrict blood flow to the heart and the brain, which can lead to heart attack and stroke. By monitoring LDL cholesterol levels, clinicians can identify patients at higher risk and take measures to manage and reduce risk, such as recommending lifestyle changes or prescribing medications like statins and an increasing set of nonstatin medications.

    “The biggest concern is that underestimating LDL cholesterol could lead to withholding treatments that would be beneficial for patients,” says Seth Martin, M.D., M.H.S., senior study author a professor of medicine at the Johns Hopkins University School of Medicine and director of the advanced lipid disorders program at the Ciccarone Center for the Prevention of Cardiovascular Disease.

    Martin, along with his colleagues, created the Martin/Hopkins method in 2013. It has since been recommended by the American College of Cardiology and the American Heart Association, and it is used by several diagnostic laboratories in the United States and around the world. Before Martin/Hopkins was developed, the Friedewald equation was the most commonly used method to gauge LDL cholesterol. However, Martin says that method and others that followed underestimate LDL cholesterol and cardiovascular disease danger for people for whom accuracy matters most: those at high risk.

    “Underestimating LDL cholesterol falsely reassures patients that their LDL cholesterol level is fine when in reality it isn’t,” says Martin. “It’s higher than the lab is reporting and warrants clinical action.”

    The study also revealed the Martin/Hopkins algorithm to be the most accurate across multiple patient subgroups based on age, sex, triglyceride (fat in the bloodstream) levels and fasting status, as well as patients with atherosclerotic cardiovascular disease, diabetes, hypertension, inflammation, thyroid dysfunction and kidney disease.

    “Most proposed alternatives to the Friedewald equation worsen LDL cholesterol accuracy, and their use could introduce unintended disparities in clinical care,” says Martin. “We hope labs that are still using the Friedewald method take a look at our findings and see that it’s time to progress to an LDL cholesterol calculation that better serves patients in guiding lipid treatment to prevent heart disease and strokes.”

    Johns Hopkins Medicine has made the Martin/Hopkins method publicly available, and any lab can use it for free. It can be accessed at LDLcalculator.com.

    Other researchers on the study include Christeen Samuel, Erin Michos, Roger Blumenthal and Steven Jones of the Ciccarone Center for the Prevention of Cardiovascular Disease at the Johns Hopkins University School of Medicine, Jihwan Park with the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health and Aparna Sajja with the MedStar Georgetown University Hospital-Washington Hospital Center.

    Martin and Jones were listed as co-inventors on a patent application that The Johns Hopkins University filed for the Martin/Hopkins method of LDL cholesterol equation. However, the patent application was later abandoned to enable use without intellectual property restrictions.

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  • Scientists Use Machine Learning to ‘See’ How the Brain Adapts to Different Environments

    Scientists Use Machine Learning to ‘See’ How the Brain Adapts to Different Environments

    Newswise — Johns Hopkins scientists have developed a method involving artificial intelligence to visualize and track changes in the strength of synapses — the connection points through which nerve cells in the brain communicate — in live animals. The technique, described in Nature Methods, should lead, the scientists say, to a better understanding of how such connections in human brains change with learning, aging, injury and disease.

    “If you want to learn more about how an orchestra plays, you have to watch individual players over time, and this new method does that for synapses in the brains of living animals,” says Dwight Bergles, Ph.D., the Diana Sylvestre and Charles Homcy Professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University (JHU) School of Medicine.

    Bergles co-authored the study with colleagues Adam Charles, Ph.D., M.E., and Jeremias Sulam, Ph.D., both assistant professors in the biomedical engineering department, and Richard Huganir, Ph.D., Bloomberg Distinguished Professor at JHU and Director of the Solomon H. Snyder Department of Neuroscience. All four researchers are members of Johns Hopkins’ Kavli Neuroscience Discovery Institute.

    Nerve cells transfer information from one cell to another by exchanging chemical messages at synapses (“junctions”). In the brain, the authors explain, different life experiences, such as exposure to new environments and learning skills, are thought to induce changes at synapses, strengthening or weakening these connections to allow learning and memory. Understanding how these minute changes occur across the trillions of synapses in our brains is a daunting challenge, but it is central to uncovering how the brain works when healthy and how it is altered by disease.

    To determine which synapses change during a particular life event, scientists have long sought better ways to visualize the shifting chemistry of synaptic messaging, necessitated by the high density of synapses in the brain and their small size — traits that make them extremely hard to visualize even with new state-of-the-art microscopes.

    “We needed to go from challenging, blurry, noisy imaging data to extract the signal portions we need to see,” Charles says.

    To do so, Bergles, Sulam, Charles, Huganir and their colleagues turned to machine learning, a computational framework that allows flexible development of automatic data processing tools. Machine learning has been successfully applied to many domains across biomedical imaging, and in this case, the scientists leveraged the approach to enhance the quality of images composed of thousands of synapses. Although it can be a powerful tool for automated detection, greatly surpassing human speeds, the system must first be “trained,” teaching the algorithm what high quality images of synapses should look like.

    In these experiments, the researchers worked with genetically altered mice in which glutamate receptors — the chemical sensors at synapses — glowed green (fluoresced) when exposed to light. Because each receptor emits the same amount of light, the amount of fluorescence generated by a synapse in these mice is an indication of the number of synapses, and therefore its strength.

    As expected, imaging in the intact brain produced low quality pictures in which individual clusters of glutamate receptors at synapses were difficult to see clearly, let alone to be individually detected and tracked over time. To convert these into higher quality images, the scientists trained a machine learning algorithm with images taken of brain slices (ex vivo) derived from the same type of genetically altered mice. Because these images weren’t from living animals, it was possible to produce much higher quality images using a different microscopy technique, as well as low quality images — similar to those taken in live animals — of the same views.

    This cross-modality data collection framework enabled the team to develop an enhancement algorithm that can produce higher resolution images from low quality ones, similar to the images collected from living mice. In this way, data collected from the intact brain can be significantly enhanced and able to detect and track individual synapses (in the thousands) during multiday experiments. 

    To follow changes in receptors over time in living mice, the researchers then used microscopy to take repeated images of the same synapses in mice over several weeks. After capturing baseline images, the team placed the animals in a chamber with new sights, smells and tactile stimulation for a single five-minute period. They then imaged the same area of the brain every other day to see if and how the new stimuli had affected the number of glutamate receptors at synapses.

    Although the focus of the work was on developing a set of methods to analyze synapse level changes in many different contexts, the researchers found that this simple change in environment caused a spectrum of alterations in fluorescence across synapses in the cerebral cortex, indicating connections where the strength increased and others where it decreased, with a bias toward strengthening in animals exposed to the novel environment.

    The studies were enabled through close collaboration among scientists with distinct expertise, ranging from molecular biology to artificial intelligence, who don’t normally work closely together. But such collaboration, is encouraged at the cross disciplinary Kavli Neuroscience Discovery Institute, Bergles says. The researchers are now using this machine learning approach to study synaptic changes in animal models of Alzheimer’s disease, and they believe the method could shed new light on synaptic changes that occur in other disease and injury contexts.

    “We are really excited to see how and where the rest of the scientific community will take this,” Sulam says.

    The experiments in this study were conducted by Yu Kang Xu (a Ph.D. student and Kavli Neuroscience Discovery Institute fellow at JHU), Austin Graves, Ph.D. (assistant research professor in biomedical engineering at JHU) and Gabrielle Coste (neuroscience Ph.D. student at JHU). This research was funded by the National Institutes of Health (RO1 RF1MH121539).

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  • New Study at Johns Hopkins Kimmel Cancer Center Shows Patient/Clinician Identity Differences Are Factor in Cancer Care

    New Study at Johns Hopkins Kimmel Cancer Center Shows Patient/Clinician Identity Differences Are Factor in Cancer Care

    Newswise — A new study by researchers at the Johns Hopkins Kimmel Cancer Center in collaboration with Dell Medical School, University of Minnesota, and the Vanderbilt University Medical Center, using a national data sample from the National Institutes of Health All of Us Research Program, revealed that a small but statistically significant proportion of patients with cancer, especially younger and lower-income minorities, disproportionately reported delaying care because of patient/clinician racial, gender and cultural differences.

    The study, led by student doctor and first author Vishal Patel from Dell Medical School at the University of Texas at Austin and senior author S. M. Qasim Hussaini, M.D., Chief Medical Oncology Fellow at the Johns Hopkins Kimmel Cancer Center, was published March 30 in the journal JAMA Oncology.

    The All of Us Research Program data is housed at the Vanderbilt University Medical Center.

    Hussaini, along with program leadership, led recent efforts focused on Diversity, Equity, and Inclusion within the hematology-oncology fellowship program at Johns Hopkins with a dedicated program focused on curricular development, recruitment and retention, minority engagement, and health systems research.

    The current work addresses the American Society of Clinical Oncology’s recently announced strategic action plans to improve workforce diversity and clinician preparedness, says Hussaini. The findings, he notes, directly inform policies to increase uptake of educational priorities and workforce diversification within oncology.

    “Our article provides important evidence that a lack of physician diversity may be contributing to disparities in care delivery for patients with cancer and can be harmful to patients,” says Patel.

    “This represents the kind of important research that needs to be done if we are to get optimal care to all Americans.  The greatest reason for racial health disparities in cancer outcomes is racial disparities in receipt of quality care,” says Otis W. Brawley, M.D., Bloomberg Distinguished Professor of Oncology and Epidemiology.

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  • Researchers Id Biomarkers of Response to Immunotherapy for Kidney Cancer

    Researchers Id Biomarkers of Response to Immunotherapy for Kidney Cancer

    Newswise — The number of immune cells in and around kidney tumors, the amount of dead cancer tissue, and mutations to a tumor suppressor gene called PBRM1 form a biomarker signature that can predict — before treatment begins — how well patients with kidney cancer will respond to immunotherapy, according to new research directed by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.

    In reviews of 136 kidney tumor biopsies taken for previous studies, investigators found that patients who had three positive factors — presence of immune cells in and around tumors, known as tumor-infiltrating immune cells, absence of dead cancer tissue, called necrosis, and a mutation in the PBRM1 gene — had the best overall survival at five years compared with patients who did not have this combination of factors. A report about the work was published online Feb. 21 in the journal Cell Reports Medicine.

    Therapies for patients with metastatic clear cell renal carcinoma, a type of kidney cancer, are rapidly evolving and include immunotherapy-based regimens, says lead study author Julie Stein Deutsch, M.D., a clinical fellow in dermatopathology at the Johns Hopkins University School of Medicine. However, there is an unmet need for biomarkers that can help match patients to the regimens most likely to help, she says. Such markers have been investigated in lung and other cancers, but have not shown the same predictive ability in patients with kidney cancers.

    The classic hematoxylin and eosin-stained (H&E) pathology slide — the gold standard for diagnosing and staging cancer in medical practices worldwide — has largely been overlooked as a possible source of biomarker information, Deutsch says. “There are many studies investigating biomarkers for response to immunotherapy using advanced technologies that require expensive machines and experienced technicians. The ability to use information from an H&E slide, pretreatment, to predict overall survival of patients receiving this therapy is extremely powerful, and is something that can be used in resource-poor settings as well,” she says.

    Immunotherapies that target PD-1 (programmed cell death 1), a protein found on immune cells, can unleash an immune response against cancer cells and has become a vanguard of cancer therapy, says senior author Janis Taube, M.D., M.Sc., co-director of the Tumor Microenvironment Laboratory at the Bloomberg~Kimmel Institute for Cancer Immunotherapy and director of the Division of Dermatopathology. However, she points out that anti-PD-1 immunotherapies do not work in all patients. The new findings could be used to help preselect patients for the most appropriate therapy, says Taube.

    Investigators examined H&E slides from 136 metastatic tumor samples, before treatment, from patients with renal cell cancers to determine the biomarker potential of this commonly available material. They reviewed 63 biopsies obtained before treatment from patients who received the immunotherapy nivolumab as a first cancer treatment or later treatment; 58 biopsies from patients receiving later-line nivolumab or the chemotherapy drug everolimus; and 15 biopsies from patients who hadn’t received therapy before, who received nivolumab plus the immunotherapy ipilimumab. Researchers scored the specimens for the amount of tumor-infiltrating immune cells (here called TILplus) and presence of necrosis (dead tissue).

    In the first group of 63 biopsies, and in samples from all three groups of patients who received immunotherapy, patients with specimens that had immune infiltrates (e.g., tumor-infiltrating lymphocytes, macrophages, plasma cells) interfacing with tumor (TILplus score of 1) showed improved overall survival compared with those without (i.e., specimens with TILplus score of 0). Median overall survival was 47.9 months in those with a TILplus score of 1 versus 16 months in those with a score of 0. Median progression-free survival was 7.5 months in those with a TILplus score of 1 versus 2.7 months in those with a score of 0. However, TILplus score was not associated with overall survival among patients receiving everolimus, indicating the findings were specific to immunotherapy.

    The presence of necrosis was found to modify the benefits of having immune system infiltration in the tumor. In two groups of biopsies studied, patients whose tumors had substantial necrosis (greater than 10% surface area) had lower overall survival compared with patients who had the same TILplus score but whose tumors lacked necrosis. This finding was observed in patients from two cohorts. Again, combining TILplus and necrosis scores was not predictive of outcomes for patients receiving everolimus.

    “This is important, because traditionally, areas of necrosis are often excluded from biomarker studies because it can’t be used for genomic or transcriptomic studies since the tissue is dead,” Deutsch says. “We show there is important information in that necrotic area that’s conferring some sort of negative disadvantage to patients. It’s important not to overlook these areas when you’re investigating biomarkers that predict how patients are going to do.”

    Finally, investigators looked at mutations in the PBRM1 gene and how that impacts the other factors. Such mutations were correlated with overall survival but were not associated with TILplus. However, a statistical analysis of all three factors found that the combination of H&E scoring with PBRM1 mutation status stratified patients into three groups. Patients who had all three positive factors — a TILplus score of 1, necrosis score of 0 and a PBRM1 mutation — had the best overall survival at five years. Patients with two of the three features demonstrated intermediate survival, while those with only one feature had the worst survival.

    When investigators performed a literature search, they were unable to find other studies that used H&E features as part of tumor characterization using multimodality approaches. “This demonstrates the underutilization of these insights in biomarker discovery for immunotherapies,” Deutsch says.

    Taube says next steps will include validating the findings in larger groups of patients and potentially prospectively in a clinical trial.

    In addition to Taube and Deutsch, study co-authors were Evan J. Lipson, Ludmila Danilova, Suzanne L. Topalian, Jaroslaw Jerdych, Ezra Baraban, Yasser Ged, Nirmish Singla, Toni K. Choueiri, Saurabh Gupta, Robert J. Motzer, David McDermott, Sabina Signoretti and Michael Atkins. Other institutions participating in the research were Dana-Farber Cancer Institute in Boston, Bristol-Myers Squibb, Memorial Sloan Kettering Cancer Center in New York, Beth Israel Deaconess Medical Center in Boston and the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

    The work was supported by The Mark Foundation for Cancer Research, Bristol-Myers Squibb, a Sidney Kimmel Cancer Center Core Grant (P30 CA006973), the National Cancer Institute (R01 CA142779), the National Institutes of Health (grants T32 CA193145 and R50 CA243627), Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16 and Program 5P30CA006516-56), the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund, Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

    Taube reported grants and consulting fees from Bristol-Myers Squibb and Akoya Biosciences, consulting for Merck, AstraZeneca, Genentech, GlaxoSmithKline, Regeneron, Lunaphone and Compugen outside this work. Deutsch and Taube filed an institutional patent on machine learning for scoring pathologic response to immunotherapy. These relationships are managed by The Johns Hopkins University in accordance with its conflict of interest policies.

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  • New Computer Model Tracks Origin of Cell Changes That Drive Development

    New Computer Model Tracks Origin of Cell Changes That Drive Development

    Newswise — Scientists at Johns Hopkins Medicine say they have developed a computer model — dubbed quantitative fate mapping — that looks back in the developmental timeline to trace the origin of cells in a fully grown organism. The new model, they say, can help researchers more precisely spot which cells acquire alterations during development that change an organism’s fate from healthy to disease states, including cancer and dementia.

    The achievement, described in the Nov. 23 issue of Cell, uses mathematical algorithms that take into account the general speed with which cells divide and differentiate, the rate at which mutations naturally accumulate and other known factors of organism development.

    “We can use this method to examine the development of organisms from cell samples, including those from non-model organisms such as humpback whales that we don’t ordinarily study,” says Reza Kalhor, Ph.D., assistant professor of biomedical engineering, genetic medicine, molecular biology and genetics and neuroscience at The Johns Hopkins University and School of Medicine. “For example, with a cell sample from the carcass of a humpback whale, we can understand how it developed as an embryo.”

    The new computer model is based on the fact that every complex living organism comes from a single, fertilized cell, or zygote. That cell divides, and the daughter cells continue dividing, eventually differentiating into specialized cells in tissues. Humans, for example, have about 70 trillion individual cells and several thousand types of cells.

    Each time a cell divides, a mutation can occur, and that alteration gets passed on to the daughter cells, which divide again, perhaps acquiring a second mutation, both of which are passed to their daughter cells, and so on. The mutations act as a kind of barcode that is detectable with genomic sequencing equipment. Scientists can track these mutations in reverse order to construct a cell’s lineage, they say.

    The quantitative fate mapping program has two parts. One is a computer program called Phylotime, which reads cell mutations as barcodes to infer the timescale associated with cell divisions. The name Phylotime stands for Phylogeny Reconstruction Using Likelihood of Time. In biology, phylogeny describes and depicts lines of evolutionary development. The second part developed by the Johns Hopkins team is a computer algorithm called ICE-FASE, which creates a model of the hierarchy and lineages of cells within an organism based on the timescales of cell divisions.

    To test the computer model, the Johns Hopkins team induced mutations in human induced pluripotent cells (iPSCs) at certain locations in the genome and at random times. Such iPSCs give rise to nearly any cell in the human body. They cultured the cells and let them divide, following the original mutation and ones that occurred spontaneously in subsequent daughter cells.

    At the end of the experiment, the researchers performed genomic sequencing on the final group of daughter cells and entered any mutations they found into the computer model.

    The result was a kind of family tree extending from the original human iPSC.

    The researchers can construct an ancestry of mature cells by comparing the combinations of mutations and drawing a far more precise picture of how the organism developed. They tested the model with computer simulations of mouse cells and human iPSCs.

    Kalhor says the new tool can help scientists compare normal versus disease states in organisms, including humans. “This tool may be helpful in showing how and when cells deviate from the normal path, which can aid the development of disease prevention tools or curative therapies,” adds Kalhor.

    The so-called cell “fate maps” developed by the quantitative fate mapping tool provide a history of cell fate determination events that happened during an organism’s development, but unlike genomic sequencing studies alone, the new tool shows when the fate commitment occurred and the relationship of a large number of different cell types in the population, says Weixiang Fang, Ph.D., postdoctoral fellow in the department of biomedical engineering at Johns Hopkins and first author of the study.

    While the computer model can construct how and when cells develop in an organism, it cannot determine whether the spontaneous mutations occur because of external, internal or random factors.

    Fang and Kalhor have made Phylotime free to use by other scientists, and it is available online.

    The research was supported by the Simons Foundation, the National Institutes of Health and the David and Lucile Packard Foundation.

    Other scientists who contributed to the research include Hongkai Ji, Ph.D., professor of biostatistics at the Johns Hopkins Bloomberg School of Public Health, who co-supervised the study, as well as Claire Bell, Abel Sapirstein, Soichiro Asami, Kathleen Leeper and Donald Zack from Johns Hopkins.

    DOI: 10.1016/j.cell.2022.10.028

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  • ‘Tis The Season to Focus on Your Mental Health

    ‘Tis The Season to Focus on Your Mental Health

    FOR IMMEDIATE RELEASE

    Newswise — The holidays are usually a time for joy and celebration. But, this merry season can be stressful for some folks. According to a poll by the American Psychiatric Association, Americans are five times more likely to say their level of stress increases rather than decreases (41% to 7%) during the holidays. Johns Hopkins Medicine experts can provide tips for managing your mental health amid the bustle of the holiday season.

    The Holiday Blues and Seasonal Affective Disorder: What’s the difference?

    For some people, the holidays can trigger feelings of sadness, loss and anxiety associated with stress, missing loved ones or negative feelings from past memories of the holidays. These feelings are considered the holiday blues, and are usually temporary.

    However, when the holiday blues persist for a longer period of time, it could be seasonal affective disorder (SAD), a type of depression that can happen during certain seasons of the year, typically fall or winter. Symptoms may include low mood or anxiety that worsens in the winter, as well as changes in sleep, appetite and energy. SAD can impact a person’s ability to work, their social interactions and quality of life. Lindsay Standeven, M.D., and Paul Nestadt, M.D., assistant professors of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, are available for media interviews about the holiday blues and SAD, and can provide tips on how to cope and help ease the symptoms.

    Older children and teens may also experience SAD. Johns Hopkins Children’s Center clinical psychologist Joseph McGuire, Ph.D., M.A., is available for interviews to discuss the signs and symptoms parents should look out for to best help their children.

    In addition, Neda Gould, Ph.D., clinical psychologist and director of the Johns Hopkins Mindfulness Program, is available for interviews on the following topics:

    Holiday Self-Care for Caregivers

    For those taking care of a loved one with a mental illness, caregiving can be physically and emotionally exhausting — and particularly taxing during the holidays. According to an AARP survey, nearly 7 in 10 caregivers say it is stressful to care for their loved one during the holiday season. To cope and avoid burnout, Gould can discuss how mindfulness can help caregivers stay in the present and de-stress over the holidays.

    Taking the Stress Out of Holiday Shopping

    Gift-giving can be fulfilling, but it might be a source of anxiety and economic distress. According to a poll from the American Psychiatry Association, adults are most likely to be worried about affording (46%) and finding (40%) holiday gifts. If the pressure of finding the perfect gift is getting to you, Gould can provide tips to keep in mind while holiday shopping.

    Making and Keeping New Year’s Resolutions

    How many times have you made a New Year’s resolution and given up on it after a few months? Whether it’s to exercise, eat healthier or quit smoking, making a realistic plan and identifying potential obstacles might be the answer to make your resolutions a reality. Gould can discuss how to set attainable goals for the new year. 

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