Snapshot of Science for October 2022

Welcome to our Snapshot of Science for October 2022.

Here's a quick look at some recent publications, press releases and stories about the Mass General Research Institute community.

In this issue we highlight:

25 new studies published in high-impact journals, along with 22 summaries submitted by the research teams
7 new research-related press releases from the Mass General Public Affairs office
6 posts from the Mass General Research Institute blog

Publications

Standardizing Treatment of Necrotizing Enterocolitis Benefits Patients in NICU
Standardizing the Evaluation and Management of Necrotizing Enterocolitis in a Level IV NICU
Aurora M, Keyes ML, Acosta JG, Swartz K, Lombay J [et al.], Matute JD
Published in Pediatrics on September 27, 2022 | *Summary available

Genetic Contributors to BP May Identify Individuals With High CVD Risk Earlier
Measured Blood Pressure, Genetically Predicted Blood Pressure, and Cardiovascular Disease Risk in the UK Biobank
Cho SMJ, Koyama S, Ruan Y, Lannery K, Wong M [et al.], Natarajan P
Published in JAMA Cardiology on September 28, 2022 | *Summary available

Sedation of Patients Recovering From Cardiac Arrest May Have a Protective Effect on Subsequent Brain Function
Post-cardiac Arrest Sedation Promotes Electroencephalographic Slow-wave Activity and Improves Survival in a Mouse Model of Cardiac Arrest
Ikeda T, Amorim E, Miyazaki Y, Kato R, Marutani E [et al.], Ichinose F
Published in Anesthesiology on September 28, 2022 | *Summary available | Press Release

Barriers to Follow Up on Abnormal Cancer Screening Test Results
Primary Care Practitioner Perceptions on the Follow-up of Abnormal Cancer Screening Test Results
Atlas SJ, Tosteson ANA, Burdick TE, Wright A, Breslau ES [et al.], Haas JS
Published in JAMA Network Open on September 29, 2022 | *Summary available

Bionic Pancreas Associated With a Greater Reduction in Glycated Hemoglobin
Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes
Bionic Pancreas Research Group, Russell SJ, Beck RW, Damiano ER, El-Khatib FH [et al.], Dauber A
Published in New England Journal of Medicine on September 29, 2022

Predicting Metastatic Potential and Patient Survival in Kidney Cancer
A Transcriptional Metastatic Signature Predicts Survival in Clear Cell Renal Cell Carcinoma
Alchahin AM, Mei S, Tsea I, Hirz T, Kfoury Y [et al.], Baryawno N
Published in Nature Communications on September 30, 2022 | *Summary available

A Scoring System for Symptom Severity in Ileoanal Pouch Patients
Development and Validation of a Symptom Based Scoring System for Bowel Dysfunction after Ileoanal Pouch Reconstruction: The Ileoanal Pouch Syndrome Severity Score
Cavallaro P, Bordeianou L; PROPS Scientific Committee
Published in Annals of Surgery on September 30, 2022 | *Summary available

Molecular Subpopulation of Interest for FGFR Inhibitors in Cholangiocarcinoma
FGFR mRNA Expression in Cholangiocarcinoma and its Correlation With FGFR2 Fusion Status and Immune Signatures
Sridharan V, Neyaz A, Chougule A, Baiev I, Reyes S [et al.], Goyal L
Published in Clinical Cancer Research on October 3, 2022 | *Summary available

Hearts Donated After Circulatory Death Performed Similar to Hearts Donated After Brain Death
Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death
D'Alessandro DA, Wolfe SB, Osho AA, Drezek K, Prario MN [et al.], Lewis GD
Published in Journal of the American College of Cardiology on October 4, 2022 | *Summary available

Columns of Brain Activity in Response to Social Cues of Personal Space Intrusions
Interdigitated Columnar Representation of Personal Space and Visual Space in Human Parietal Cortex
Tootell RBH, Nasiriavanaki Z, Babadi B, Greve DN, Nasr S, Holt DJ
Published in Journal of Neuroscience on October 5, 2022 | *Summary available

Maternal Consumption of Ultra-processed Food During Pregnancy Associated With Increased Risk of Overweight or Obesity in Offspring
Maternal Consumption of Ultra-processed Foods and Subsequent Risk of Offspring Overweight or Obesity: Results From Three Prospective Cohort Studies
Wang Y, Wang K, Du M, Khandpur N, Rossato SL [et al.], Chan AT
Published in BMJ on October 5, 2022 | *Summary available

Natural Language Processing to Predict Risk of Maternal Morbidity
Comparison of Natural Language Processing of Clinical Notes With a Validated Risk-Stratification Tool to Predict Severe Maternal Morbidity
Clapp MA, Kim E, James KE, Perlis RH, Kaimal AJ, McCoy TH Jr, Easter SR
Published in JAMA Network Open on October 5, 2022 | *Summary available

Researchers Developed an Imaging Agent for Demyelination and Tested in Humans
Human Biodistribution and Radiation Dosimetry of the Demyelination Tracer [18F]3F4AP
Brugarolas P, Wilks MQ, Noel J, Kaiser JA, Vesper DR [et al.], El Fakhri G
Published in European Journal of Nuclear Medicine and Molecular Imaging on October 5, 2022 | *Summary available | Press Release

New CRISPR-Cas Approach Permits More Precise DNA Cleavage
Precise DNA Cleavage Using CRISPR-SpRYgests
Christie KA, Guo JA, Silverstein RA, Doll RM, Mabuchi M [et al.], Kleinstiver BP
Published in Nature Biotechnology on October 6, 2022 | *Summary available | Press Release

New Insights Into Ovary Cell Types
A Single-Cell Atlas of the Cycling Murine Ovary
Morris ME, Meinsohn MC, Chauvin M, Saatcioglu HD, Kashiwagi A [et al.], Pépin D
Published in eLife on October 7, 2022 | *Summary available

A Genetic System for On Demand Generation of Molecular Oxygen in Living Cells
A Genetically Encoded System for Oxygen Generation in Living Cells
Markhard AL, McCoy JG, To TL, Mootha VK
Published in PNAS on October 10, 2022 | Press Release

Increased Familiarity Between Nurses and Residents Led to Higher Team Performance on Complex Cognitive Tasks in Medical Simulations
Effect of Increased Interprofessional Familiarity on Team Performance, Communication, and Psychological Safety on Inpatient Medical Teams: A Randomized Clinical Trial
Iyasere CA, Wing J, Martel JN, Healy MG, Park YS, Finn KM
Published in JAMA Internal Medicine on October 10, 2022 | *Summary available

A Systematic Whole Genome Scan for Blood Lipids
Whole Genome Sequence Analysis of Blood Lipid Levels in >66,000 Individuals
Selvaraj MS, Li X, Li Z, Pampana A, Zhang DY [et al.], Natarajan P
Published in Nature Communications on October 11, 2022 | *Summary available

A General Solution to the Cryopreservation of a Broad Spectrum of Cellular, Organismal and Tissue-based Biosystems
Rapid Joule Heating Improves Vitrification-based Cryopreservation
Zhan L, Han Z, Shao Q, Etheridge ML, Hays T, Bischof JC
Published in Nature Communications on October 12, 2022 | *Summary available

Neighborhood Conditions Explain Substantial Variability in Life Expectancy
Association of Neighborhood Conditions and Resources for Children With Life Expectancy at Birth in the U.S.
Shanahan KH, Subramanian SV, Burdick KJ, Monuteaux MC, Lee LK, Fleegler EW
Published in JAMA Network Open on October 14, 2022 | *Summary available

Benefits of Sac/Val in Heart Failure Preserved Across All Dose Categories
Dose-response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction
Mohebi R, Liu Y, Piña IL, Prescott MF, Butler J [et al.], Januzzi JL Jr
Published in Journal of the American College of Cardiology on October 18, 2022 | *Summary available

Antibody-based Therapy Eliminates Circulating Tumor Cells in Mouse Models of Breast and Pancreatic Cancer
Targeting Breast and Pancreatic Cancer Metastasis Using a Dual-Cadherin Antibody
Micalizzi DS, Che D, Nicholson BT, Edd JF, Desai N [et al.], Haber DA
Published in PNAS on October 18, 2022 | *Summary available | Press Release

Genes Contribute to Alternative Lengthening of Telomeres
TERRA and RAD51AP1 Promote Alternative Lengthening of Telomeres Through an R- to D-loop Switch
Yadav T, Zhang JM, Ouyang J, Leung W, Simoneau A, Zou L
Published in Molecular Cell on October 19, 2022

Riboflavin Depletion Promotes Lifespan and Healthspan in C. Elegans
Riboflavin Depletion Promotes Longevity and Metabolic Hormesis in Caenorhabditis Elegans
Yerevanian A, Murphy LM, Emans S, Zhou Y, Ahsan FM [et al.], Soukas AA
Published in Aging Cell on September 30, 2022 | *Summary available

Comparison of Omicron BA.2 Severity With Earlier Forms of COVID-19
Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England
Strasser ZH, Greifer N, Hadavand A, Murphy SN, Estiri H
Published in JAMA Network Open on October 25, 2022 | *Summary available | Press Release

Publication Summaries

Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disease and a leading cause of morbidity and mortality in Neonatal Intensive Care Units (NICUs). Management is variable due to the lack of evidence-based recommendations. This quality improvement (QI) project investigated the institutional variation of NEC management and developed a standardized guideline within our Level IV NICU at Mass General. Variation in care decreased after the initiation of this guideline and supporting electronic medical record tools, resulting in fewer days of exposure to broad-spectrum antibiotics and fasting in patients evaluated and managed for NEC without an increase in morbidity or mortality. Therefore, a QI approach can benefit patients and decrease variability even in diseases with limited evidence-based standards.

(Summary submitted by Juan D. Matute, MD, Neonatal Intensive Care Unit, Mass General Hospital for Children)

Genetic Contributors to BP May Identify Individuals with High CVD Risk Earlier
Measured Blood Pressure, Genetically Predicted Blood Pressure, and Cardiovascular Disease Risk in the UK Biobank
Cho SMJ, Koyama S, Ruan Y, Lannery K, Wong M [et al.], Natarajan P
Published in JAMA Cardiology on September 28, 2022

Hypertension is the major contributor to cardiovascular disease (CVD), but variability in measured blood pressure (BP) challenges sustained management. To better inform treatment and control strategies, we examined whether genetic predisposition to high BP, summarized as polygenic risk score, is associated with CVD event independent of measured BPs and antihypertensive medication. We discovered that BP genetic risk identified one in 10 with normal measured BP who had similar CVD risk as those with untreated hypertension. Similarly, one in 4 with untreated hypertension carried comparable CVD risk as those prescribed antihypertensives. Given the ability to ascertain genetic risk early in life, genetic BP may identify individuals with high CVD risk earlier on and augment current guideline-directed therapy.

(Summary submitted by So Mi Jemma Cho, PhD, Cardiovascular Research Center, Department of Medicine)

Patients who survive a cardiac arrest, but remain unresponsive after resuscitation, are often treated with sedation. Whether sedation is the optimal approach to improving the chance of survival and recovery of normal brain function is unknown. We studied a mouse model of cardiac arrest and found that the sedatives propofol or dexmedetomidine improved survival rate and recovery of normal brain function. Paradoxically, sedation appeared to stimulate the mouse to wake up from coma. In contrast, mice that did not receive sedation after cardiac arrest showed decreased brain activity for many hours. These findings suggest that sedation of patients recovering from cardiac arrest does in fact have a protective effect on subsequent brain function.

(Summary submitted by Fumito Ichinose, MD, PhD, Department of Anesthesia, Critical Care and Pain Medicine)

We surveyed practitioners from three primary care networks in New England, including Massachusetts General Hospital, on their perceptions of support for the follow-up of abnormal breast, cervical, colorectal and lung cancer screening tests. Despite practitioners working within networks with well-developed electronic health record systems, fewer than half reported that they were very satisfied with their ability to manage abnormal results for any of these cancer screening tests. Though specialists were often involved in managing these results, primary care practitioners felt they continued to be responsible for following up on overdue, abnormal results. We believe these results reflect the fragmented nature of the follow-up of abnormal cancer screening test results and support the need for integrated systems that take a primary care, holistic, population-based approach.

(Summary submitted by Steven J. Atlas, MD, MPH, Practice-Based Research & Quality Improvement, Department of Medicine)

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer in adults. Single-cell transcriptomic analysis of ccRCC primary and metastatic tumors reveals a distinct transcriptional signature that is predictive of metastatic potential and patient survival. The findings will lead to earlier detection of metastatic potential from ccRCC patients, better monitoring of these patients over time and eventually adjusted treatment options.

(Summary submitted by Shenglin Mei, PhD, Center for Regenerative Medicine, Department of Medicine)

A Scoring System for Symptom Severity in Ileoanal Pouch Patients
Development and Validation of a Symptom Based Scoring System for Bowel Dysfunction After Ileoanal Pouch Reconstruction: The Ileoanal Pouch Syndrome Severity Score
Cavallaro P, Bordeianou L; PROPS Scientific Committee
Published in Annals of Surgery on September 30, 2022

The Patient Reported Outcomes after Pouch Surgery (PROPS) Delphi consensus study was a patient-centered effort that identified the key functional outcomes and consequences that are most important to patients living with ileoanal pouches. The recently published PROPS II study is a second stage of this project and aimed to survey a large group of pouch patients to develop a clinical scoring system using the previously identified outcomes. The study ultimately developed the Ileoanal Pouch Syndrome Severity Score—a patient-centered, clinically useful scoring system that can quantify the range and severity of symptoms experienced by ileoanal pouch patients and their correlation with quality of life. This tool will help identify patients with severe Ileoanal Pouch Syndrome and will be able to help assess efficacy of medical and surgical interventions to improve quality of life.

(Summary submitted by Paul Cavallaro, MD, Department of Surgery)

A Molecular Subpopulation of Interest for FGFR Inhibitors in Cholangiocarcinoma
FGFR mRNA Expression in Cholangiocarcinoma and its Correlation With FGFR2 Fusion Status and Immune Signatures
Sridharan V, Neyaz A, Chougule A, Baiev I, Reyes S [et al.], Goyal L
Published in Clinical Cancer Research on October 3, 2022

Cholangiocarcinomas are a rare but aggressive malignancy of the bile ducts. In recent years, targeted therapies have been approved that target a subset of tumors harboring FGFR2 gene fusions or rearrangements. However, gaps remain in identifying patients that may respond to these drugs. Our study correlates genetic signatures in cholangiocarcinoma with gene expression and immune markers to show that many patients that don't have FGFR gene fusions still have high FGFR gene expression. This work provides molecular epidemiological data to evaluate the usefulness of these targeted therapies in this broader subpopulation of patients.

(Summary submitted by Vishwajith Sridharan, MD, MBA, Department of Medicine)

The Heart Transplant team at Mass General was proud to share our experience using hearts from donors after circulatory death (DCD). While traditionally, hearts from non-heart beating donors were discarded, we now have a machine which gives us the ability to resuscitate and evaluate organs that are removed postmortem. This technique was recently evaluated in a national clinical trial which our team co-led and demonstrated this method to be safe and reliable. Our team has continued to lead the nation in demonstrating the favorable impact of this practice on getting our patients quickly and safely through heart transplantation.

(Summary submitted by David A. D'Alessandro, MD, Division of Cardiac Surgery, Department of Surgery)

We recently published a study that provides new insights about how the human brain generates personal space - the physical distance that people unconsciously need from other people. Using a powerful form of brain imaging that generates very detailed maps of brain responses, our team identified columns in the brain that respond specifically to intrusions into personal space. These types of columns respond to social cues rather than just very basic sensory information and have not been observed before in the human brain. Follow-up work is investigating how these columns communicate with different brain areas and whether this communication is disrupted in disorders such as schizophrenia.

(Summary submitted by Daphne Holt, MD, PhD, Martinos Center, Department of Psychiatry)

Maternal Consumption of Ultra-processed Food During Pregnancy Associated With an Increased Risk of Overweight or Obesity in Offspring
Maternal Consumption of Ultra-processed Foods and Subsequent Risk of Offspring Overweight or Obesity: Results From Three Prospective Cohort Studies
Wang Y, Wang K, Du M, Khandpur N, Rossato SL [et al.], Chan AT
Published in BMJ on October 5, 2022

Ultra-processed foods are commonly found in contemporary Western-style diets and are associated with weight gain in adults. Yet, it is unclear whether there is a transgenerational association between maternal consumption of ultra-processed foods and offspring body weight. We report that maternal consumption of ultra-processed foods during the child-rearing period was associated with an increased risk of overweight or obesity in offspring. These findings suggest that mothers may benefit from limiting intake of ultra-processed foods to prevent offspring obesity and highlight the importance of refining dietary recommendations and removing financial/social barriers to improve nutrition for women of child-bearing age.

(Summary submitted by Long H. Nguyen, MD, MS, Division of Gastroenterology, Department of Medicine)

In this study, a natural language processing-based risk-stratification method using clinical documentation from the start of the delivery encounter performed as well as a validated obstetric risk score for predicting severe maternal morbidity. The findings suggest that machine learning and advanced analytics using electronic health record data, like free text documentation, have potential applications in obstetrics to improve maternal care while reducing non-patient-facing tasks for clinical staff.

(Summary submitted by Mark A. Clapp, MD MPH, Department of Obstetrics Gynecology & Reproductive Biology)

In this study, four healthy volunteers (two females) underwent a whole-body PET scan with a new PET tracer called [18F]3F4AP. PET tracers are short-lived radiolabeled drugs that need to be made onsite just before use and testing a new tracer in humans is a considerable enterprise. They require approval from the FDA, which looks closely at how the tracer is made and ensures that it is safe to use in humans. In this study, there were no safety concerns or adverse events and the radiation dose from the tracer was found to be lower than expected. Furthermore, images of the tracer showed it distributed widely throughout the body and into the brain opening the door to future studies examining the ability of the tracer to detect demyelinated lesions in the brain.

(Summary submitted by Pedro Brugarolas, PhD, Gordon Center for Medical Imaging, Department of Radiology)

DNA cutting enzymes have created and transformed fields such as molecular biology by enabling the rapid and facile manipulation of DNA in test tubes. However, until now, no enzymes permitted simple and programmable cutting of DNA at any specific base (since restriction enzymes, CRISPR-Cas proteins, argonaute proteins, etc., all have sequence constraints). Here we developed and applied a CRISPR-Cas enzyme that can cut DNA at any nucleotide, giving researchers the ability, for the first time, to precisely manipulate nucleic acids in vitro. The use of our engineered SpRY enzyme for DNA digests (so-called SpRYgests) to cut DNA can be implemented in straightforward, rapid, and inexpensive workflows. We envision numerous applications of SpRYgests, from molecular cloning, to saturation mutagenesis, to molecular library preparation (i.e., for next-generation sequencing), together expediting and improving the precision of DNA manipulations in vitro.

(Summary submitted by Ben Kleinstiver, PhD, Center for Genomic Medicine)

The ovary is a highly dynamic organ, whose cellular composition and physiological function changes depending on the stage of the estrous cycle. In this study we used single-cell RNA sequencing to survey the cyclic changes in cell states that underly the structural remodeling and cellular differentiation occurring in the mouse ovary across a range of reproductive states. In this cellular atlas we describe unexpected complexity in cell types, propose new cellular markers, and identify secreted factors that vary by estrous stage, and could thus be used as biomarkers for assisted reproduction.

(Summary submitted by David Pépin, MD, Department of Surgery)

While teamwork is critical in delivering high quality medical care, little research has evaluated the impact of interprofessional familiarity on inpatient team performance. We studied interactions between medical residents and nurses to determine the impact of increased familiarity on team performance, psychological safety, and communication. Fifteen residents were randomized to complete all their general medical rotations on one clinical floor with the same group of nurses. We found that increased familiarity improved team performance on standardized medical simulations, increased the likelihood that a nurse was present on inpatient rounds, and enhanced nursing perception of teamwork culture earlier in the academic year. Given the increased reliance on interprofessional teams in healthcare delivery, medical centers should consider team familiarity as a potential metric to improve physician-nursing teamwork and patient care.

(Summary submitted by Christiana A. Iyasere, MD, MBA, Department of Medicine)

Lipids are key contributors and known genetic risk factors for cardiovascular diseases. Modification of lipid levels is governed by various elements including diet, exercise, and genetics. The contribution of rare non-coding variation, which forms the bulk of the genome to lipids and other traits, has been unknown due to prior genomic profiling and methodologic limitations. We studied 66,000 ancestrally diverse individuals with whole genome sequencing to profile rare non-coding variation. We used these new genetic data and new methods to describe a previously unrecognized rare non-coding genetic model for lipids. Not only does this expand our understanding of the genetic contributors to lipids, it may also improve the diagnostic yield of genetic testing for lipid disorders in the near future.

(Summary submitted by Margaret S. Selvaraj, PhD, Cardiovascular Research Center, Department of Medicine)

A General Solution to the Cryopreservation of a Broad Spectrum of Cellular, Organismal and Tissue-based Biosystems
Rapid Joule Heating Improves Vitrification Based Cryopreservation
Zhan L, Han Z, Shao Q, Etheridge ML, Hays T, Bischof JC
Published in Nature Communications on October 12, 2022

We developed a rapid (up to hundreds of millions °C/min) and scalable joule heating approach to improve the cryopreservation of biological systems. These systems range in size from cells (µm) to organisms (Drosophila embryos) to tissue slices (mm) and we demonstrate the ability to tailor the rewarming rates to achieve optimal outcomes in these biosystems.

(Summary submitted by Li Zhan, PhD, Center for Engineering in Medicine & Surgery, Shriners Burn Institute)

Neighborhood Conditions Explain Substantial Variability in Life Expectancy.
Association of Neighborhood Conditions and Resources for Children With Life Expectancy at Birth in the U.S.
Shanahan KH, Subramanian SV, Burdick KJ, Monuteaux MC, Lee LK, Fleegler EW
Published in JAMA Network Open on October 14, 2022

This study investigated whether neighborhood conditions and resources for children are associated with life expectancy at birth in the United States. We used the Child Opportunity Index to capture neighborhood conditions and resources for children that impact health. In the cross-sectional analysis of over 65,000 census tracts, communities with the lowest neighborhood conditions had a life expectancy that was seven years lower than life expectancy in those with the strongest neighborhood conditions. Neighborhood conditions explained substantial variability in life expectancy. The findings suggest neighborhood conditions and resources for children are important targets for policy to advance health equity.

(Summary submitted by Kristen H. Shanahan, MD, Department of Emergency Medicine)

Suboptimal sacubitril/valsartan (Sac/Val) dosage is common. The mechanistic benefit of Sac/Val at lower than target dose is unclear. In our study, 794 persons with heart failure with reduced ejection fraction were categorized according to average daily doses of Sac/Val. Change from baseline to 12 months in cardiac biomarkers, health status, and echocardiographic measures were assessed. We observed similar changes in cardiac biomarkers and gains in Kansas City Cardiomyopathy Questionnaire-23 across dose categories. Moreover, consistent reverse cardiac remodeling in all dose categories occurred. These results imply the mechanistic benefits of Sac/Val in heart failure with reduced ejection fraction are preserved across all dose categories.

(Summary submitted by Reza Mohebi, MD, Cardiovascular Research Center, Department of Medicine)

We identified an antibody-based treatment that works on circulating tumor cells (CTCs) and could inform the development of new therapies to prevent the spread of cancer. This treatment was shown to be effective at eliminating CTCs in mouse models of breast and pancreatic cancer and had no adverse effects on normal healthy tissue. This therapy may be more effective at targeting CTCs because these antibodies have better access to the circulating cells traveling in the bloodstream and are highly specific to CTCs compared to the surrounding blood cells. The results suggest that this approach could be effective at targeting diverse types of CTCs. With more research and development, therapies that use this approach could be used to prevent cancers from spreading and improve long term survival.

Riboflavin Depletion Promotes Lifespan and Healthspan in C. Elegans
Riboflavin Depletion Promotes Longevity and Metabolic Hormesis in Caenorhabditis Elegans
Yerevanian A, Murphy LM, Emans S, Zhou Y, Ahsan FM [et al.], Soukas AA
Published in Aging Cell on September 30, 2022

Riboflavin is a water-soluble vitamin that is not produced by the body and must be acquired through the diet. We studied the effects of depleting riboflavin in a type of roundworms called C. elegans, which share similar metabolic systems with humans and are often used to model human diseases. Our team used gene knockdown to reduce riboflavin levels in worms by 90%. Depleting levels of riboflavin provided unexpected health and longevity benefits in an animal model of aging.

In this retrospective cohort study of 101,470 patients, in-hospital mortality rates were 0.7% for Delta (B.1.617.2), 0.4% for the original Omicron (B.1.1.529) variant, and 0.3% for the Omicron BA.2 subvariant. After adjusting for a number confounding factors, the risk of death was significantly lower with the Omicron subvariant BA.2 compared with those of the Omicron and Delta variants. Observational data that adjusts for confounders suggest that the Omicron BA.2 variant is intrinsically less severe than previous variants.

(Summary submitted by Zachary Strasser, MD, MBA, Laboratory of Computer Science, Department of Medicine)

Press Releases

Radiotracer That Detects an Important Contributor to Neurological Diseases Tested for the First Time in Humans
Featuring Pedro Brugarolas, PhD, Moses Wilks, PhD, and Georges El Fakhri, PhD

Demyelination—the loss of the protective insulating layer around neurons—contributes to many neurological diseases but can be difficult to detect. Researchers at Mass General have developed an imaging agent for demyelination and evaluated its use in healthy human volunteers.

Researchers Develop System for Generating Oxygen Within Cells
Featuring Vamsi K. Mootha, MD

With a newly developed technology, scientists can engineer cells to produce oxygen on demand in response to an added chemical. The advance can be used to evaluate the role of oxygen within cells and may have a variety of clinical uses in the future.

New CRISPR-Cas Approach Permits More Precise DNA Cleavage
Featuring Benjamin Kleinstiver, PhD

Investigators have overcome major shortcomings of tools to cut and edit DNA, including CRISPR-Cas technologies. The advance enables the ability to cut DNA at practically any sequence in the lab, including many sequences that were previously untargetable.

Antibody-based Therapy Eliminates Circulating Tumor Cells in Mouse Models of Breast and Pancreatic Cancer
Featuring David T. Ting, MD

Researchers have developed an antibody-based therapy that targets circulating tumor cells in mouse models of breast and pancreatic cancer. The therapy, which targets proteins called cadherins, is effective against single cells in circulation but does not suppress the formation of tumors, nor does it elicit detectable toxicity in normal organs.

After Cardiac Arrest, Does Sedation Improve the Chance of Surviving and Regaining Normal Brain Function?
Featuring Fumito Ichinose, MD, PhD

Administering the sedatives propofol or dexmedetomidine when circulation is restored following cardiac arrest improved survival and brain function in mice. The findings suggest that sedation of patients recovering from cardiac arrest in the intensive care unit may have protective effects on the brain.

New Mitochondrial Disease Identified in Identical Twins
Featuring Vamsi K. Mootha, MD

In a set of identical twins, investigators have discovered a disease that affects the mitochondria, or the specialized compartments within cells that produce energy. Unlike in other mitochondrial diseases, mitochondria were hyperactive in these cases, so that even though the siblings had a high intake of calories, their body weights remained very low.

How Severe is the SARS-CoV-2 Omicron BA.2 Subvariant Compared With Earlier Variants?
Featuring Zachary Strasser, MD, MBA

In an analysis of COVID-19 cases from Mass General Brigham's electronic health record system, mortality rates were 0.7% for the SARS-CoV-2 Delta variant, 0.4% for the original Omicron variant, and 0.3% for the Omicron BA.2 subvariant. After adjustments, the odds of death were more than 2-times higher for the Delta and original Omicron variants compared with Omicron BA.2. Patients with Delta and original Omicron variants were also more likely to need hospitalizations, invasive ventilation, and intensive care admissions. The comprehensive digital surveillance system can continue to be used to measure SARS-CoV-2's intrinsic severity over time.

Blog Posts

Mass General Research Awards and Honors: August and September 2022
The talented and dedicated researchers working at the Mass General Research Institute are pushing the boundaries of science and medicine every day. In this Research Awards and Honors series, we highlight some of the individuals who have recently received awards or honors for their research achievements.

Hispanic Heritage Month: Highlighting the Hispanic Voices in Mass General's Research Community
Featuring Sophia Kamran, MD, Santiago Lozano-Calderon, MD, PhD, Davide Perez, MD, MMSC, and Liliana Ramierez Gomez, MD

Each year, Hispanic Heritage Month is observed throughout the United States from September 15 to October 15, celebrating the history, culture and uniqueness of Hispanic Heritage. In honor of Hispanic Heritage Month, we're honored to highlight the voices, culture and cutting-edge work of researchers at Massachusetts General Hospital with Hispanic roots.

Should We Be Turning the Dial Down Instead of Up When It Comes to Vitamins?
Featuring Armen Yerevanian, MD

Investigators at Mass General found significantly depleting levels of riboflavin in C. elegens worms provided unexpected health benefits.

MGH Endowed Research Institute Chair Celebration Highlights a Visionary Approach to Translational Sciences
Featuring Gabriela Apiou, PhD

Gabriela Apiou, PhD, was named the inaugural incumbent of the Endowed MGH Research Institute Chair in Translational Sciences.

Through the Magnifying Glass: The Metabolism Unit
Featuring Steven Grinspoon, MD

Learn more about the individual labs and centers in our #ThroughTheMagnifyingGlass series, where we take a closer look at the teams that make up the Massachusetts General Research Institute. Our inaugural research team is the Metabolism Unit within the Division of Endocrinology in the Department of Medicine at Mass General, which is led by Steven Grinspoon, MD.

Breast Cancer Awareness Month: Q&A featuring Manisha Bahl, MD, MPH

Dr. Bahl is using artificial intelligence and deep learning to improve the detection, diagnosis, and treatment of breast cancer.

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Snapshot of Science for October 2022