Welcome to our Snapshot of Science for March 2021

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 20 summaries submitted by the research teams
  • 17 new research-related press releases from the Mass General Public Affairs office
  • 11 posts from the Mass General Research Institute blog
Publications

ELECTRICAL BRAIN STIMULATION DRIVES LEARNING
Electrical Stimulation of the Macaque Ventral Tegmental Area Drives Category-selective Learning Without Attention
Murris SR, Arsenault JT, Raman R, Vogels R, Vanduffel W
Published in Neuron on February 25, 2021 | *Summary available


SMS REMINDERS TO TAKE MEDICATION
Effect of SMS Reminders on PrEP Adherence in Young Kenyan Women (MPYA study): A Randomised Controlled Trial
Haberer JE, Bukusi EA, Mugo NR, Pyra M, Kiptinness C [et al.], Ngure K, Baeten JM; MPYA Study Team
Published in Lancet HIV on March 01, 2021 | *Summary available


ADDICTION TREATMENT FOR PEOPLE EXPERIENCING HOMELESSNESS
Office-based Addiction Treatment Retention and Mortality Among People Experiencing Homelessness
Fine DR, Lewis E, Weinstock K, Wright J, Gaeta JM, Baggett TP
Published in JAMA Network Open on March 01, 2021 | *Summary available


AI SCREENING FOR CHILDHOOD BLINDNESS
Applications of Artificial Intelligence for Retinopathy of Prematurity Screening
Campbell JP, Singh P, Redd TK, Brown JM, Shah PK [et al.], Kalpathy-Cramer J
Published in Pediatrics on March 01, 2021 | *Summary available


FREQUENT INPATIENT ASSESSMENTS TO PREDICT POSTDISCHARGE SUICIDE ATTEMPTS
A Pilot Study Using Frequent Inpatient Assessments of Suicidal Thinking to Predict Short-Term Postdischarge Suicidal Behavior
Wang SB, Coppersmith DDL, Kleiman EM, Bentley KH, Millner AJ, [et al.], Nock MK
Published in JAMA Network Open on March 01, 2021 | *Summary available


CT PROTOCOLS FOR COVID-19 PATIENTS
Variations in CT Utilization, Protocols, and Radiation Doses in COVID-19 Pneumonia: Results from 28 Countries in the IAEA Study
Homayounieh F, Holmberg O, Umairi RA, Aly S, Basevičius A [et al.], Vassileva J
Published in Radiology on March 01, 2021 | *Summary available


PATIENT PREFERENCE FOR STATIN THERAPY
Patient Preference Distribution for Use of Statin Therapy
Brodney S, Valentine KD, Sepucha K, Fowler FJ Jr, Barry MJ
Published in JAMA Network Open on March 01, 2021 | *Summary available


PHYSICIAN HANDOFF DOES NOT INCREASE MORTALITY
Assessment of Care Handoffs Among Hospitalist Physicians and 30-Day Mortality in Hospitalized Medicare Beneficiaries
Farid M, Tsugawa Y, Jena AB
Published in JAMA Network Open on March 01, 2021


HIGH BMI ASSOCIATED WITH COVID-19 HOSPITALIZATION
Cardiometabolic Risk Factors for COVID-19 Susceptibility and Severity: A Mendelian Randomization Analysis
Leong A, Cole JB, Brenner LN, Meigs JB, Florez JC, Mercader JM
Published in PLoS Medicine on March 04, 2021 | *Summary available


MECHANISMS OF RESISTANCE TO CRIZOTINIB AND LORLATINIB
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer
Lin JJ, Choudhury NJ, Yoda S, Zhu VW, Johnson TW [et al.], Gainor JF
Published in Clinical Cancer Research on March 08, 2021


COHESIN EVICTION AND RETENTION BALANCE REGULATES X INACTIVATION
Balancing Cohesin Eviction and Retention Prevents Aberrant Chromosomal Interactions, Polycomb-mediated Repression, and X-inactivation
Kriz AJ, Colognori D, Sunwoo H, Nabet B, Lee JT
Published in Molecular Cell on March 08, 2021 | Press Release


IMMUNOSEQUENCING EXTRACELLULAR VESICLES
Sequencing-based Protein Analysis of Single Extracellular Vesicles
Ko J, Wang Y, Sheng K, Weitz DA, Weissleder R
Published in ACS Nano on March 09, 2021 | *Summary available


REVEALING TWIN APOBEC MUTATION HOTSPOTS
An Extended APOBEC3A Mutation Signature in Cancer
Langenbucher A, Bowen D, Sakhtemani R, Bournique E [et al.], Lawrence MS
Published in Nature Communications on March 11, 2021 | *Summary available


VACCINE EFFICACY AGAINST SARS-COV-2 VARIANTS
Multiple SARS-CoV-2 Variants Escape Neutralization by Vaccine-induced Humoral Immunity
Garcia-Beltran WF, Lam EC, St Denis K, Nitido AD, Garcia ZH [et al.], Balazs AB
Published in Cell on March 12, 2021 | *Summary available


COMBINATION APPROACH FOR TREATING ADVANCED HR+/HER2- BREAST CANCER
Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR+/HER2- Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1)
Bardia A, Hurvitz SA, DeMichele A, Clark AS, Zelnak A [et al.], Moulder-Thompson S
Published in Clinical Cancer Research on March 15, 2021


SACITUZUMAB GOVITECAN FOR ADVANCED SOLID TUMORS
Sacituzumab Govitecan, a Trop-2-Directed Antibody-Drug Conjugate, for Patients with Epithelial Cancer: Final Safety and Efficacy Results from the Phase 1/2 IMMU-132-01 Basket Trial
Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L [et al.], Ocean AJ
Published in Annals of Oncology on March 16, 2021 | *Summary available


METABOLIC COST OF EXERCISE IN HFPEF PATIENTS VS COMMUNITY DWELLING ADULTS
Metabolic Cost of Exercise Initiation in Patients with Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults
Shah RV, Schoenike MW, Armengol de la Hoz MÁ, Cunningham TF, Blodgett JB [et al.], Lewis GD
Published in JAMA Cardiology on March 17, 2021


THE VALUE OF STATISTICAL SUICIDE PREDICTION
Accuracy Requirements for Cost-effective Suicide Risk Prediction Among Primary Care Patients in the U.S.
Ross EL, Zuromski KL, Reis BY, Nock MK, Kessler RC, Smoller JW
Published in JAMA Psychiatry on March 17, 2021 | *Summary available | Press Release


SINGLE INJECTION OF GENE THERAPY TO REDUCE TAU
Persistent Repression of Tau in the Brain Using Engineered Zinc Finger Protein Transcription Factors
Wegmann S, DeVos SL, Zeitler B, Marlen K, Bennett RE [et al.], Hyman BT
Published in Science Advances on March 19, 2021 | *Summary available | Press Release


TARGETING MITOCHONDRIAL PRODUCTION
Malic Enzyme 2 Connects the Krebs Cycle Intermediate Fumarate to Mitochondrial Biogenesis
Wang YP, Sharda A, Xu SN, van Gastel N, Man CH, Choi U, Leong WZ, Li X, Scadden DT
Published in Cell Metabolism on March 23, 2021 | *Summary available


ASSESSING AGE DIFFERENCES IN RISK FACTORS FOR HEART FAILURE
Age Dependent Associations of Risk Factors with Heart Failure: Pooled Population Based Cohort Study
Tromp J, Paniagua SMA, Lau ES, Allen NB, Blaha MJ [et al.], Ho JE
Published in The BMJ on March 23, 2021 | *Summary available


COST-EFFECTIVE METHOD TO DETECT NOVEL VARIATIONS AMONG NON-EUROPEANS
Low-coverage Sequencing Cost-effectively Detects Known and Novel Variation in Underrepresented Populations
Martin AR, Atkinson EG, Chapman SB, Stevenson A, Stroud RE [et al.], Zingela Z
Published in American Journal of Human Genetics on March 24, 2021 | *Summary available


AML PATIENTS REPORT PTSD SYMPTOMS ONE MONTH AFTER CHEMOTHERAPY INITIATION
Posttraumatic Stress Disorder (PTSD) Symptoms in Patients with Acute Myeloid Leukemia (AML)
Amonoo HL, LeBlanc TW, Kavanaugh AR, Webb JA, Traeger LN [et al.], El-Jawahri A
Published in Cancer on March 25, 2021 | *Summary available


LAKE LOUISE CRITERIA PROVIDES IMPORTANT DIAGNOSTIC VALUE
Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients with Immune Checkpoint Inhibitor-Associated Myocarditis
Thavendiranathan P, Zhang L, Zafar A, Drobni ZD, Mahmood SS [et al.], Neilan TG
Published in Journal of the American College of Cardiology on March 30, 2021 | *Summary available


ANALYTIC CHARACTERISTICS OF HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS
Discordance of High-Sensitivity Troponin Assays in Patients with Suspected Acute Coronary Syndromes
Karády J, Mayrhofer T, Ferencik M, Nagurney JT, Udelson JE [et al.], Koenig W, Hoffmann U
Published in Journal of the American College of Cardiology on March 30, 2021 | *Summary available


Publication Summaries

ELECTRICAL BRAIN STIMULATION DRIVES LEARNING
Electrical Stimulation of the Macaque Ventral Tegmental Area Drives Category-selective Learning Without Attention
Murris SR, Arsenault JT, Raman R, Vogels R, Vanduffel W
Published in Neuron on February 25, 2021

A radiologist instantly recognizes a small spot on an MR image as a tumor, which is invisible for most of us. The radiologist acquired this exquisite skill through many years of practice, a phenomenon known as perceptual learning. Past research showed that people can improve their perception for stimuli, even when they are not consciously aware of the "learned" stimulus. We showed that by electrical stimulation of a ventral brain region producing dopamine in monkeys, one can induce perceptual learning for complex stimuli and associated brain plasticity in the absence of directed attention to such stimuli.

(Summary submitted by Wim Vanduffel, PhD, Department of Radiology, Martinos Center for Biomedical Imaging)


SMS REMINDERS TO TAKE MEDICATION
Effect of SMS Reminders on PrEP Adherence in Young Kenyan Women (MPYA study): A Randomised Controlled Trial
Haberer JE, Bukusi EA, Mugo NR, Pyra M, Kiptinness C [et al.], Ngure K, Baeten JM; MPYA Study Team
Published in Lancet HIV on March 01, 2021

Young women in sub-Saharan Africa want and need good HIV prevention options, and PrEP (emtricitabine/tenofovir) is a highly effective HIV prevention tool when taken daily. However, PrEP adherence has been challenging for many, especially among young women. This randomized controlled trial among 348 high-risk young women in Kenya sought to learn whether SMS reminders could help support PrEP adherence. We found high interest in PrEP, yet adherence declined steadily over time and the reminders had no significant effect on adherence. Future research is necessary to improve adherence to PrEP; promising approaches include longer acting PrEP formulations, community-based PrEP delivery systems and stigma-reduction interventions.

(Summary submitted by Jessica Haberer, MD, Center for Global Health, Department of Medicine)


ADDICTION TREATMENT FOR PEOPLE EXPERIENCING HOMELESSNESS
Office-based Addiction Treatment Retention and Mortality Among People Experiencing Homelessness
Fine DR, Lewis E, Weinstock K, Wright J, Gaeta JM, Baggett TP
Published in JAMA Network Open on March 01, 2021

Outpatient-based addiction treatment programs have been established across the country to address the opioid overdose crisis. This study evaluated one such program designed specifically for people experiencing homelessness, a population in which one in four deaths is caused by drug overdose. Results showed that program attendance was associated with reduced risk of death, regardless of ongoing illicit opioid use. However, retention in the program was low. These findings highlight the importance of addiction treatment programming for people experiencing homelessness while underscoring the need for future research on ways to enhance retention in care.

(Summary submitted by Danielle Fine, MD, Division of General Internal Medicine, Department of Medicine)


AI SCREENING FOR CHILDHOOD BLINDNESS
Applications of Artificial Intelligence for Retinopathy of Prematurity Screening
Campbell JP, Singh P, Redd TK, Brown JM, Shah PK [et al.], Kalpathy-Cramer J
Published in Pediatrics on March 01, 2021

Childhood blindness from retinopathy of prematurity (ROP) is increasing in many parts of the world. This is a result of improved neonatal survival after preterm birth in the setting of under resourced health systems with limited ability to monitor oxygen and provide screening. Evaluation of an artificial intelligence system in an ROP tele-screening program in India revealed high accuracy for detection of sight-threatening ROP. By using a quantitative scale, it was found that units with oxygen-monitoring capability had lower ROP severity.

(Summary submitted by Praveer Singh, PhD, Department of Radiology, Martinos Center for Biomedical Imaging)


FREQUENT INPATIENT ASSESSMENTS TO PREDICT POSTDISCHARGE SUICIDE ATTEMPTS
A Pilot Study Using Frequent Inpatient Assessments of Suicidal Thinking to Predict Short-Term Postdischarge Suicidal Behavior
Wang SB, Coppersmith DDL, Kleiman EM, Bentley KH, Millner AJ, [et al.], Nock MK
Published in JAMA Network Open on March 01, 2021

The risk of suicide is extremely elevated in the weeks following discharge from a psychiatric hospitalization and we currently lack the ability to accurately predict which patients are most at risk. We installed smartphone apps on patients phones while they were in the hospital that asked them to report on the severity of their suicidal thinking 4-6 times per day throughout their hospital stay. We found that data from those surveys allowed us to predict with a fairly high degree of accuracy which patients made a suicide attempt in the month after leaving the hospital. These findings may help to improve our ability to help those patients most at risk for suicide after hospitalization.

(Summary submitted by Matthew K. Nock, PhD, Department of Psychiatry)


CT PROTOCOLS FOR COVID-19 PATIENTS
Variations in CT Utilization, Protocols and Radiation Doses in COVID-19 Pneumonia: Results from 28 Countries in the IAEA Study
Homayounieh F, Holmberg O, Umairi RA, Aly S, Basevičius A [et al.], Vassileva J
Published in Radiology on March 01, 2021

Chest CT is a frequently performed test in COVID-19 infection for its initial diagnosis, and for assessing patients with moderate to severe disease and complications. Compared to chest X-rays, chest CT gives several-fold higher radiation dose. Mass General partnered with the International Atomic Energy Agency (IAEA) to find out when and how CT is used in 54 CT facilities from 28 countries in 782 patients with known or suspected COVID-19 infection. Several facilities (22%) used CT to make the initial diagnosis of COVID-19 due to lack of serological tests. There were 8-10-fold variations in radiation doses from chest CT. Older CT scanners and technologies had higher radiation doses as compared to the newer ones. The study found a lack of uniform policy on use of CT in COVID-19 patients.

(Summary submitted by Mannudeep Kalra, MD, Divisions of Thoracic & Cardiovascular Imaging, Department of Radiology)


PATIENT PREFERENCE FOR STATIN THERAPY
Patient Preference Distribution for Use of Statin Therapy
Brodney S, Valentine KD, Sepucha K, Fowler FJ Jr, Barry MJ
Published in JAMA Network Open on March 01, 2021

Statins reduce the risk of heart attacks or strokes, but how much good they do depend on patients' risk: the higher the risk, the more benefit. To find out how patients' feelings about taking a statin varied by the size of their risk, we gave adults personalized information about the benefits and harms of the medicine. No surprise, we found that as risk of heart attacks or strokes increased, more patients wanted a statin, but the point at which a clear majority of patients wanted a statin was very high. That tells us most decisions about when to prescribe a statin need to be informed by a shared decision process to find out what patients want.

(Summary submitted by Suzanne Brodney, PhD, Health Decision Sciences Center)


HIGH BMI ASSOCIATED WITH COVID-19 HOSPITALIZATION
Cardiometabolic Risk Factors for COVID-19 Susceptibility and Severity: A Mendelian Randomization Analysis
Leong A, Cole JB, Brenner LN, Meigs JB, Florez JC, Mercader JM
Published in PLoS Medicine on March 04, 2021

Epidemiological studies have shown that people with certain underlying medical conditions are more likely to develop severe illness from COVID-19. We used a statistical genetics technique called Mendelian randomization to test whether 17 cardiometabolic risk factors have a causal relationship with contracting COVID-19 or hospitalization for COVID-19. We found that higher body mass index was the only risk factor that was associated with a higher risk of hospitalization for COVID-19 compared to the general population. Our study provides genetic evidence supporting the notion that obesity may have amplified the COVID-19 pandemic directly or through obesity-related medical conditions—type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease.

(Summary submitted by Aaron Leong, MD, MSc, Division of Endocrinology, Department of Medicine)


IMMUNOSEQUENCING EXTRACELLULAR VESICLES
Sequencing-based Protein Analysis of Single Extracellular Vesicles
Ko J, Wang Y, Sheng K, Weitz DA, Weissleder R
Published in ACS Nano on March 09, 2021

Extracellular vesicles (EV) have emerged as promising biomarkers, drug delivery vesicles and treatment modulators. While different types of vesicles are being explored for these applications, it is becoming clear that human EV are quite heterogenous even when collected from homogenous cell populations. To resolve the heterogeneity, we developed an immunosequencing method that allows multiplexed measurement of protein molecules from single EV. We use droplet microfluidics to compartmentalize and barcode individual EV and sequencing to determine protein composition. Using this highly sensitive technology, we detected specific proteins at the single EV level. We expect that this technology (SEIseq) will be useful for immunotyping of single circulating vesicles and improve disease detection.

(Summary submitted by Jina Ko, PhD, Center for Systems Biology)


REVEALING TWIN APOBEC MUTATION HOTSPOTS
An Extended APOBEC3A Mutation Signature in Cancer
Langenbucher A, Bowen D, Sakhtemani R, Bournique E [et al.], Lawrence MS
Published in Nature Communications on March 11, 2021

A major cause of cancer mutations is APOBEC enzymes, which cancer cells can hijack to mutagenize their own DNA. APOBEC enzymes are famous for the "tell-tale TpC signature" they leave in DNA, mutating C bases that have a T before them. Here, we show that even sites without a preceding T can also be APOBEC mutation hotspots when they occur in a DNA "hairpin" structure, illustrating how DNA sequence and DNA structure contribute additively to the APOBEC mutation signature. Our results clarify the "Genomic Twin Paradox" of closely spaced pairs of mutation hotspots in cancer genomes, revealing that they are twin APOBEC mutation hotspots.

(Summary submitted by Michael S. Lawrence, PhD, Department of Pathology, Mass General Cancer Center)


VACCINE EFFICACY AGAINST SARS-COV-2 VARIANTS
Multiple SARS-CoV-2 Variants Escape Neutralization by Vaccine-induced Humoral Immunity
Garcia-Beltran WF, Lam EC, St Denis K, Nitido AD, Garcia ZH [et al.], Balazs AB
Published in Cell on March 12, 2021

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. We evaluated the neutralization potency of BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Our data suggests that the antibodies raised by two of the existing vaccines neutralize P.1/P.2 and B.1.351 variants less well than the original Wuhan strain. Despite our results, it's important to consider that vaccines raise other kinds of immune responses that could protect against severe disease. Given the implications, we should expand SARS-CoV-2 genomic surveillance efforts to closely monitor circulating variants and determine whether they have the potential to infect and cause disease in vaccinated individuals.

(Summary submitted by Alejandro Balazs, PhD, Ragon Institute of MGH, MIT and Harvard)


SACITUZUMAB GOVITECAN FOR ADVANCED SOLID TUMORS
Sacituzumab Govitecan, a Trop-2-Directed Antibody-Drug Conjugate, for Patients with Epithelial Cancer: Final Safety and Efficacy Results from the Phase 1/2 IMMU-132-01 Basket Trial
Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L [et al.], Ocean AJ
Published in Annals of Oncology on March 16, 2021

Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets trop-2, a glycoprotein that is overexpressed in multiple solid tumors. This report summarizes the safety and efficacy data from a basket phase 1/2 clinical trial evaluating SG for patients with advanced solid tumors. Overall, the drug was well tolerated with the most frequent treatment-related adverse events being nausea, diarrhea, neutropenia, alopecia and fatigue. Evidence of clinical activity, with objective response rates coupled with disease control, were apparent across small disease cohorts, validating Trop-2 as a broad therapeutic target in solid tumors.

(Summary submitted by Aditya Bardia, MD, MPH, Division of Hematology/Oncology, Mass General Cancer Center)


THE VALUE OF STATISTICAL SUICIDE PREDICTION
Accuracy Requirements for Cost-effective Suicide Risk Prediction Among Primary Care Patients in the U.S.
Ross EL, Zuromski KL, Reis BY, Nock MK, Kessler RC, Smoller JW
Published in JAMA Psychiatry on March 17, 2021 | Press Release

Several mathematical models have been developed to predict which patients are at high risk of suicide, but it's not known how accurate these models must be in order to be cost-effective. In this study, we determined that suicide risk prediction could be cost-effective if its positive predictive value is above 1%-2%—that is, if more than 1-2 out of every 100 patients deemed to be high-risk go on to make a suicide attempt. Our results suggest that several suicide risk prediction models are already accurate enough to be cost-effective in the United States primary care setting.

(Summary submitted by Eric Ross, MD, Department of Psychiatry)


SINGLE INJECTION OF GENE THERAPY TO REDUCE TAU
Persistent Repression of Tau in the Brain Using Engineered Zinc Finger Protein Transcription Factors
Wegmann S, DeVos SL, Zeitler B, Marlen K, Bennett RE [et al.], Hyman BT
Published in Science Advances on March 19, 2021

We have used a genetic engineering strategy to silence the expression of the gene that codes for tau—a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer’s disease—in an animal model of the condition. Mice with Alzheimer’s disease received a single injection of the treatment—which employed a harmless virus to deliver the ZFP-TFs to cells—directly into the hippocampus region of the brain or intravenously into a blood vessel. Treatment with ZFP-TFs reduced tau protein levels in the brain by 50% to 80% in 11 months, the longest time point studied. Importantly, the therapy reversed some of the Alzheimer’s-related damage present in animal brain cells.

(Summary submitted by Bradley T. Hyman, MD, PhD, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease)


TARGETING MITOCHONDRIAL PRODUCTION
Malic Enzyme 2 Connects the Krebs Cycle Intermediate Fumarate to Mitochondrial Biogenesis
Wang YP, Sharda A, Xu SN, van Gastel N, Man CH, Choi U, Leong WZ, Li X, Scadden DT
Published in Cell Metabolism on March 23, 2021

The powerhouse within our cells that all cells depend upon is the mitochondria. When our cells need more energy, they make more mitochondria. How mitochondria know to make more of themselves is largely unknown. We discovered that when mitochondria are active, a byproduct signals mitochondria to make more of themselves. This happens through a mitochondrial protein, malic enzyme 2 or ME2. We are now targeting ME2 to turn on or off mitochondria production as mitochondria, and their function are linked to settings from exercise capacity to cancer to Alzheimer's.

(Summary submitted by David Scadden, MD, Center for Regenerative Medicine, Mass General Cancer Center)


ASSESSING AGE DIFFERENCES IN RISK FACTORS FOR HEART FAILURE
Age Dependent Associations of Risk Factors with Heart Failure: Pooled Population Based Cohort Study
Tromp J, Paniagua SMA, Lau ES, Allen NB, Blaha MJ [et al.], Ho JE
Published in The BMJ on March 23, 2021

We investigated age-related differences in risk for new-onset heart failure in a pooled population-based cohort study consisting of 24,675 individuals from the United States and the Netherlands. We found that young people (

(Jasper Tromp, PhD, National Unversity of Singapore)


COST-EFFECTIVE METHOD TO DETECT NOVEL VARIATIONS AMONG NON-EUROPEANS
Low-coverage Sequencing Cost-effectively Detects Known and Novel Variation in Underrepresented Populations
Martin AR, Atkinson EG, Chapman SB, Stevenson A, Stroud RE [et al.], Zingela Z
Published in American Journal of Human Genetics on March 24, 2021

GWAS play a powerful role in determining how genetic variants affect risk for various diseases. However, because most GWAS data has been gathered from people of European descent, their accuracy—and ability to uncover new variants—is limited in underrepresented groups. The NeuroGAP-Psychosis study team has shown that low-coverage next-generation sequencing provides a cost-effective alternative to commonly-used GWAS arrays for populations of non-European descent. We demonstrated that sequencing coverage as low as 4x allows for the identification of variants that haven't been observed in other populations, while keeping costs comparable to traditional GWAS approaches.

(Summary submitted by Alicia Martin, PhD, Analytic & Translational Genetics Unit, Department of Medicine)


AML PATIENTS REPORT PTSD SYMPTOMS ONE MONTH AFTER CHEMOTHERAPY INITIATION
Posttraumatic Stress Disorder (PTSD) Symptoms in Patients with Acute Myeloid Leukemia (AML)
Amonoo HL, LeBlanc TW, Kavanaugh AR, Webb JA, Traeger LN [et al.], El-Jawahri A
Published in Cancer on March 25, 2021

Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy face a life-threatening illness, isolating hospitalization and substantial physical and psychological symptoms. In this study, we examined the relationship between PTSD symptoms with baseline sociodemographic factors, coping skills and quality of life (QOL). Our results suggest that a substantial proportion (28%) of patients with AML report clinically significant PTSD symptoms one-month after initiating intensive chemotherapy. Patients' baseline QOL, coping strategies and extent of QOL decline during hospitalization emerge as important risk factors for PTSD, underscoring the need for supportive oncology interventions to reduce risk of PTSD in this population.

(Summary submitted by Hermioni Lokko Amonoo, MD, MPP, Department of Psychiatry)


LAKE LOUISE CRITERIA PROVIDES IMPORTANT DIAGNOSTIC VALUE
Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients with Immune Checkpoint Inhibitor-Associated Myocarditis
Thavendiranathan P, Zhang L, Zafar A, Drobni ZD, Mahmood SS [et al.], Neilan TG
Published in Journal of the American College of Cardiology on March 30, 2021

Immune checkpoint inhibitors (ICIs) are novel immunotherapies that are being applied in an expanding range of cancers. Myocarditis is an uncommon, but serious, toxicity associated with ICI use. With myocarditis, there is cardiac inflammation and cardiac fibrosis. Parametric mapping is a cardiac magnetic resonance technique that provides quantitative assessments of cardiac inflammation and fibrosis. In this paper, we provide the first data on the use of parametric mapping in the diagnosis of ICI-associated myocarditis. We found that quantitative measurements of cardiac edema and fibrosis are highly useful in the diagnosis of ICI myocarditis and, additionally, in determining prognosis in ICI myocarditis.

(Amna Zafar, MD, Department of Radiology)


ANALYTIC CHARACTERISTICS OF HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS
Discordance of High-Sensitivity Troponin Assays in Patients with Suspected Acute Coronary Syndromes
Karády J, Mayrhofer T, Ferencik M, Nagurney JT, Udelson JE [et al.], Koenig W, Hoffmann U
Published in Journal of the American College of Cardiology on March 30, 2021

The concordance of three high-sensitivity troponin (hs-cTn) assays (Elecsys2010, Roche Diagnostics; ARCHITECT i2000SR, Abbott Diagnostics; hsVista, Siemens Diagnostics) recently cleared by the FDA is unknown. In a patient cohort with suspected acute coronary syndrome, the three assays classified blood samples in agreement into the same analytical benchmark category in 37.4% (384/1,027 samples), when one timepoint troponin measurement was used. In 242 patients for whom serial troponin testing was available the assays agreed to recommend similar management in 74.8%. Overall, clinicians should be aware that the discordance between hs-cTn assays is significant enough that management recommendations may change for e.g. a patient who is transferred from one hospital to another using different hs-cTn assays.

(Summary submitted by Julia Karády, PhD, Department of Radiology)


Press Releases

Artificial Intelligence Reveals Current Drugs That May Help Combat Alzheimer's Disease
Featuring Mark Albers, MD, PhD

Researchers at Mass General and Harvard Medical School have developed an artificial intelligence-based method to screen currently available medications as possible treatments for Alzheimer's disease.


MGH Researchers Call for Greater Awareness of Delayed Skin Reactions after Moderna COVID-19 Vaccine
Featuring Aleena Banerji, MD, Kimberly Blumenthal, MD, MSc, Ruth Foreman, MD, Esther Freeman, MD, PhD Lacey Robinson, MD, Rebecca Saff, MD, PhD, Erica Shenoy, MD, PhD, and Anna Wolfson, MD

As the speed and scale of vaccinations against the SARS-CoV-2 virus ramps up globally, researchers at Mass General are calling for greater awareness and communication around a delayed injection-site reaction that can occur in some patients who have received the Moderna mRNA-1273 vaccine.


The Implications of Swollen Lymph Nodes Following COVID-19 Vaccination
Featuring Leslie Lamb, MD, MSc, and Constance Lehman, MD, PhD

Radiologists at Mass General who recently published an approach to managing post COVID vaccination swollen lymph nodes in women who receive mammograms for breast cancer screening in the American Journal of Roentgenology have now expanded their recommendations to include care for patients who undergo other imaging tests for diverse medical reasons.


Atherosclerosis Can Accelerate the Development of Clonal Hematopoiesis, Study Finds
Featuring Kamila Naxerova, PhD

In a new study, researchers at Mass General and Harvard Medical School now suggest that atherosclerosis causes clonal hematopoiesis. Patients with atherosclerosis suffer from hyperlipidemia and inflammation, two conditions that are known to chronically boost hematopoietic stem cell division rates.


Are Higher Obesity Rates in Minority Groups a Product of Systemic Racism?
Featuring Fatima Cody Stanford, MD, MPH, MPA

The higher rates of obesity in Black, Indigenous and People of Color (BIPOC) compared with other groups in the United States can be attributed in large part to systemic racism, according to a new perspective article. The authors offer a 10-point strategy to study and solve the public health issues responsible for this disparity.


Real World Data Reveal Risks of Allergic Reactions after Receiving COVID-19 mRNA Vaccines
Featuring Aleena Banerji, MD, Kimberly Blumenthal, MD, MSc, Lacey Robinson, MD, and Erica Shenoy, MD, PhD

Real world data on the first mRNA-based COVID-19 vaccinations among employees at Mass General Brigham provide reassurances of the rarity of such serious reactions and the ability to recover from them.


Study Reveals New Clues about the Architecture of X Chromosomes
Featuring Jeannie T. Lee, MD, PhD

Researchers at Mass General have uncovered new clues that add to the growing understanding of how female mammals, including humans, "silence" one X chromosome. Their new study demonstrates how certain proteins alter the architecture of the X chromosome, which contributes to its inactivation. Better understanding of X chromosome inactivation could help scientists figure out how to reverse the process, potentially leading to cures for devastating genetic disorders.


Vaccine-induced Antibodies May Be Less Effective Against Several New SARS-CoV-2 Variants
Featuring Alejandro Balazs, PhD

Understanding how well the COVID-19 vaccines work against these variants is vital in the efforts to stop the global pandemic and is the subject of new research from the Ragon Institute of MGH, MIT and Harvard and Mass General.


Heart-healthy Lifestyles Linked to Lower Risk of Future Cancers
Featuring Emily S. Lau, MD, and Jennifer E. Ho, MD

In addition to lowering risk of heart disease, maintaining a heart-healthy lifestyle may pay off in lower risk for developing cancer, researchers from Mass General and other centers in the United States and the Netherlands have found.


Common Antibiotic Can Safely Be Given to Most Surgery Patients Despite Penicillin Allergy
Featuring Kimberly Blumenthal, MD, MSc

Most surgical patients with a history of penicillin allergy can safely be given the guideline-recommended antibiotic cefazolin to prevent infection instead of several penicillin alternatives that are less effective and more expensive, according to a study conducted by Mass General, the University of Colorado Anschutz Medical Campus and the University of Porto in Portugal.


Suicide Risk Prediction Models Could Be Cost-effective in Clinical Practice
Featuring Jordan Smoller, MD

Researchers at Mass General demonstrate that statistical suicide risk prevention models could be implemented cost-effectively in U.S. health care systems and might help save many lives each year.


Common, Serious Gut Disorder Is Under- and Often Misdiagnosed
Featuring Trisha Satya Pasricha, MD

Patients who regurgitate regularly but without any known cause may have a condition called rumination, which is often confused with other gastrointestinal conditions. A new study by investigators at Mass General in Neurogastroenterology and Motility clearly describes this syndrome, how to distinguish it from other conditions and how to treat it.


Large-scale Genome Analysis Identifies Differences by Sex in Major Psychiatric Disorders
Featuring Jill M. Goldstein, PhD

An analysis of sex differences in the genetics of schizophrenia, bipolar disorder and major depressive disorders indicates that while there is substantial genetic overlap between males and females, there are noticeable sex-dependent differences in how genes related to the central nervous system, immune system and blood vessels affect people with these disorders.


Pregnant Women Show Robust Immune Response to COVID Vaccines, Pass Antibodies to Newborns
Featuring Andrea Edlow, MD, MSc

In the largest study of its kind to date, researchers at Mass General, Brigham and Women's Hospital and the Ragon Institute of MGH, MIT and Harvard have found the new mRNA COVID-19 vaccines to be highly effective in producing antibodies against the SARS-CoV-2 virus in pregnant and lactating women. They also demonstrated the vaccines confer protective immunity to newborns through breastmilk and the placenta.


Researchers Identify Brain's Role in Broken Heart Syndrome
Featuring Ahmed Tawakol, MD

A new study uncovers potential mechanisms that may contribute to "broken heart syndrome," or Takotsubo syndrome (TTS), a temporary heart condition that is brought on by stressful situations and emotions. The research, which was led by investigators at Mass General, indicates that a heart-brain connection likely plays a major role.


Gene Therapy Using "Zinc Fingers" May Help Treat Alzheimer's Disease, Animal Study Shows
Featuring Bradley Hyman, MD, PhD

Researchers have used a genetic engineering strategy to dramatically reduce levels of tau, a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer's disease, in an animal model of the condition. The results, which come from investigators at Mass General and Sangamo Therapeutics Inc., could lead to a potentially promising treatment for patients with this devastating illness.


Researchers Discover Why Cold Induces Tooth Pain and Hypersensitivity—and How to Stop It
Featuring Jochen Lennerz, MD, PhD

Odontoblasts, the cells that form a tooth's dentin, have a newly discovered function: sensing cold, which can trigger pain in teeth. But scientists have also found a way to block the pathway to cold-sensitive teeth.


COVID-19-associated Seizures May Be Common, Linked to Higher Risk of Death
Featuring M. Brandon Westover, MD, PhD

This study examines the prevalence and risk factors for nonconvulsive seizures among patients hospitalized with COVID-19.


Blog Posts

Voices of Women in Science: Fatima Cody Stanford, MD, MPH, MPA

Dr. Stanford is a trailblazing obesity medicine physician-scientist at Mass General who is studying the intersection of medicine, public health, policy and disparities.


Voices of Women in Science: Madhusmita Misra, MD, MPH

Dr. Misra is an internationally known expert on neuroendocrine, metabolic and bone complications of disorders that span the weight spectrum from anorexia nervosa to obesity.


Voices of Women in Science: Margarita Alegría, PhD

Dr. Alegría is Chief of the Disparities Research Unit within the Mongan Institute at Mass General. Her research is focused on testing new models of care and interventions for improving health care and eliminating health care disparities for diverse populations.


Voices of Women in Science: Jacqueline Lane, PhD

Dr. Lane is a sleep genetics and circadian rhythms researcher investigating the connections between sleep quality and disease.


Is There A Better Way to Monitor Depression Symptoms and Treatment Response?
Featuring Paola Pedrelli, PhD

By combining smartphone data with physiological data, Dr. Paola Pedrelli is hoping to gain better insights into depression symptom severity and treatment response.


Conversations with Margarita Alegría, PhD
Featuring Margarita Alegría, PhD

Dr. Alegría recently started a monthly email series, and we loved it so much we wanted to share each month's email on Bench Press. In her first conversation, she discusses the mental health challenges of the COVID-19 pandemic and offers strategies for building a stronger mental health system.


Voices of Women in Science: Susan Slaugenhaupt, PhD

Dr. Slaugenhaupt is scientific director of the Mass General Research Institute and runs her own lab in the Center for Genomic Medicine investigating familial dysautonomia, mucolipidosis type IV and mitral valve prolapse.


Congratulations to the 2021 Claflin Distinguished Scholars (Part 1)
Congratulations to the 2021 Claflin Distinguished Scholars (Part 2)

Featuring Abigial Batchelder, PhD, MPH, Melanie S. Haines, MD, Jamie Jacobs, PhD, Marcy A. Kingsbury, PhD, Lidia Maria V. Moura, MD, Esther Rheinbay, PhD, Rebecca D. Sandlin, PhD, and Jia Yin, MD, PhD, MPH

The Women in Academic Medicine Committee, with the sponsorship of the Executive Committee on Research, established the Claflin Distinguished Scholar Awards in recognition of the fact that maintaining research productivity during child-rearing years is a significant obstacle to career advancement for a number of women.


The Pandemic Has Created a 4th Shift for Women in Medicine
Featuring Julie K. Silver, MD

Our next guest blog post is written by Julie K. Silver, MD. Dr. Silver is an associate professor and associate chair in the Department of Physical Medicine and Rehabilitation at Harvard Medical School.


Voices of Women in Science: Dorothy Jones, EdD, APRN

Dorothy Jones, EdE, APRN, is senior nurse scientist at the Yvonne L. Munn Center for Nursing Research and professor at the Boston College Connell School of Nursing.