Welcome to our Snapshot of Science for November 2020

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:

  • 30 new studies published in high impact journals, along with 23 summaries submitted by the research teams
  • 17 new research-related press releases from the Mass General Public Affairs office
  • 7 posts from the Mass General Research Institute blog
Publications

COVID-19 AND CARDIAC PATHOLOGY IN ATHLETES
Coronavirus Disease 2019 and the Athletic Heart: Emerging Perspectives on Pathology, Risks and Return to Play
Kim JH, Levine BD, Phelan D, Emery MS, Martinez MW [et al.], Baggish AL
Published in JAMA Cardiology on October 26, 2020 | Press Release


ANDROGEN RECEPTOR SIGNALING AND MELANOMA CELL GROWTH
Sustained Androgen Receptor Signaling Is a Determinant of Melanoma Cell Growth Potential and Tumorigenesis
Ma M, Ghosh S, Tavernari D, Katarkar A, Clocchiatti A [et al.], Dotto GP
Published in Journal of Experimental Medicine on October 28, 2020 | *Summary available


GLUTEN CHALLENGE CLINICAL TRIAL
Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial
Leonard MM, Silvester JA, Leffler D, Fasano A, Kelly CP [et al.], Smithson G
Published in Gastroenterology on October 29, 2020 | *Summary available


PLASMONIC SENSORS FOR EXTRACELLULAR VESICLE ANALYSIS
Plasmonic Sensors for Extracellular Vesicle Analysis: From Scientific Development to Translational Research
Chin LK, Son T, Hong JS, Liu AQ, Skog J, [et al.] Im H
Published in ACS Nano on October 29, 2020 | *Summary available


FINDINGS IN HOSPITALIZED COVID-19 PATIENTS
Laboratory Findings Associated with Severe Illness and Mortality Among Hospitalized Individuals with Coronavirus Disease 2019 in Eastern Massachusetts
Castro VM, McCoy TH, Perlis RH
Published in JAMA Network Open on October 30, 2020


SINGLE-CELL PROFILING OF EBOLA VIRUS DISEASE
Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics
Kotliar D, Lin AE, Logue J, Hughes TK, Khoury NM [et al.], Bennett RS
Published in Cell on November 02, 2020 | *Summary available


GENETIC CLUES FOR CROHN'S DISEASE
A Missense Variant in SLC39A8 Confers Risk for Crohn's Disease by Disrupting Manganese Homeostasis and Intestinal Barrier Integrity
Nakata T, Creasey EA, Kadoki M, Lin H, Selig MK [et al.], Xavier RJ
Published in PNAS on November 02, 2020 | *Summary available


DELIRIUM IN OLDER PATIENTS WITH COVID-19
Delirium in Older Patients with COVID-19 Presenting to the Emergency Department
Kennedy M, Helfand BKI, Gou RY, Gartaganis SL, Webb M [et al], Inouye SK
Published in JAMA Network Open on November 02, 2020 | *Summary available


LIVER CANCER IN PATIENTS WITH HEPATITIS C
Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients with Hepatitis C in the Era of Direct-Acting Antiviral Agents
Chen Q, Ayer T, Adee MG, Wang X, Kanwal F, Chhatwal J
Published in JAMA Network Open on November 02, 2020 | *Summary available


GOUT PREVENTION THROUGH WEIGHT LOSS
Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors
McCormick N, Rai SK, Lu N, Yokose C, Curhan GC, Choi HK
Published in JAMA Open Network on November 02, 2020 | *Summary available


DIABETES DRUG MAY REDUCE RISK OF CARDIAC EVENTS
Effects of Canagliflozin on Amino-Terminal Pro-B-Type Natriuretic Peptide: Implications for Cardiovascular Risk Reduction
Januzzi JL Jr, Xu J, Li J, Shaw W, Oh R [et al.], Hansen MK
Published in Journal of the American College of Cardiology on November 03, 2020 | *Summary available


COMPROMISED IMMUNE EVOLUTION LEADS TO COVID-19 DEATH
Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality
Zohar T, Loos C, Fischinger S, Atyeo C, Wang C [et al.], Alter G
Published in Cell on November 03, 2020 | Press Release


PREMATURE MENOPAUSE MAY BE IMPORTANT RISK FACTOR FOR AAA
Association of Premature Menopause with Risk of Abdominal Aortic Aneurysm in the Women's Health Initiative
Chou EL, Pettinger M, Haring B, Allison MA, Mell MW [et al.], Liu S
Published in Annals of Surgery on November 04, 2020 | *Summary available


BACTERIAL-HOST INTERFACE IN ENDOCARDITIS
Multimodal Imaging of Bacterial-Host Interface in Mice and Piglets with Staphylococcus Aureus Endocarditis
Panizzi P, Krohn-Grimberghe M, Keliher E, Ye YX, Grune J [et al.], Nahrendorf M
Published in Science Translational Medicine on November 04, 2020 | *Summary available


PREMATURE MENOPAUSE, CHIP AND CVD RISK
Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women
Honigberg MC, Zekavat SM, Niroula A, Griffin GK, Bick AG [et al.], Natarajan P
Published in Circulation on November 09, 2020 | *Summary available | Press Release


COUNTRY PREPAREDNESS AND QUALITY OF CLINICAL CARE FOR CVD
Association Between Country Preparedness Indicators and Quality Clinical Care for Cardiovascular Disease Risk Factors in 44 Lower- and Middle-income Countries: A Multicountry Analysis of Survey Data
Davies JI, Reddiar SK, Hirschhorn LR, Ebert C, Marcus ME [et al.], Jaacks LM
Published in PLOS Medicine on November 10, 2020 | *Summary available


PATIENT OUTCOMES AND TREATMENT RESPONSE IN GASTROINTESTINAL CANCER
Associations of Baseline Patient-Reported Outcomes with Treatment Outcomes in Advanced Gastrointestinal Cancer
van Seventer EE, Fish MG, Fosbenner K, Kanter K, Mojtahed A [et al.], Nipp RD
Published in Cancer on November 10, 2020 | *Summary available


TFEB LOCALIZATION- AND STIMULUS-SPECIFIC RESPONSES
TFEB Transcriptional Responses Reveal Negative Feedback by BHLHE40 and BHLHE41
Carey KL, Paulus GLC, Wang L, Balce DR, Luo JW [et al.], Xavier RJ
Published in Cell Reports on November 10, 2020 | *Summary available


INSURANCE EXPANSION MAY REDUCE UTILIZATION OF EMERGENCY MEDICAL SERVICES
Association of Affordable Care Act Implementation with Ambulance Utilization for Asthma Emergencies in New York City, 2008-2018
Peters GA, Ordoobadi AJ, Cash RE, Wong ML, Avillach P, Camargo, CA Jr.
Published in JAMA Network Open on November 11, 2020 | *Summary available | Press Release


SIMULATING OUTCOMES OF COVID-19 PUBLIC HEALTH STRATEGIES IN SOUTH AFRICA
Cost-effectiveness of Public Health Strategies for COVID-19 Epidemic Control in South Africa: A Microsimulation Modelling Study
Reddy KP, Shebl FM, Foote JHA, Harling G, Scott JA [et al.], Siedner MJ
Published in Lancet Global Health on November 11, 2020 | *Summary available | Press Release


CORRELATES OF PROTECTION FOLLOWING TYPHOID VACCINE
Vi-specific Serological Correlates of Protection for Typhoid Fever
Jin C, Hill J, Gunn BM, Yu WH, Dahora LC [et al.], Pollard AJ
Published in Journal of Experimental Medicine on November 12, 2020


BREAST CANCER TUMOR FORMATION AND THERAPY
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
Krug K, Jaehnig EJ, Satpathy S, Blumenberg L, Karpova A [et al.], Gillette MA
Published in Cell on November 16, 2020 | *Summary available


PATIENT TRUST IN THE SURGICAL DECISION SCALE
Validation of the Trust in the Surgical Decision Scale
Brodney S, Sepucha K, Fowler FJ Jr, Valentine KD, Barry MJ
Published in Annals of Surgery on November 16, 2020 | *Summary available


TRAPPC9 DEFICIENCY IMPAIRS LEARNING AND MEMORY
Trappc9 Deficiency in Mice Impairs Learning and Memory by Causing Imbalance of Dopamine D1 and D2 Neurons
Ke Y, Weng M, Chhetri G, Usman M, Li Y [et al.], Li X
Published in Science Advances on November 18, 2020 | *Summary available


LUNG CANCER SCREENING ELIGIBILITY AND USE
Lung Cancer Screening Eligibility and Use with Low-dose Computed Tomography: Results from the 2018 Behavioral Risk Factor Surveillance System Cross-sectional Survey
Narayan AK, Gupta Y, Little BP, Shepard JO, Flores EJ
Published in Cancer on November 18, 2020


FUNCTIONAL COMPENSATION AFTER ACUTE LIVER INJURY
Functional Compensation Precedes Recovery of Tissue Mass Following Acute Liver Injury
Walesky CM, Kolb KE, Winston CL, Henderson J, Kruft B, [et al], Goessling W
Published in Nature Communications on November 19, 2020


EVALUATING LORLATINIB FOR NSCLC
First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer
Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y [et al.], Solomon BJ
Published in New England Journal of Medicine on November 19, 2020 | Press Release


A NOVEL PORTABLE MRI SCANNER
A Portable Scanner for Magnetic Resonance Imaging of the Brain
Cooley CZ, McDaniel PC, Stockmann JP, Srinivas SA, Cauley SF [et al.], Wald LL
Published in Nature Biomedical Engineering on November 23, 2020 | *Summary available | Press Release


INTERCELLULAR SHIGELLA SPREAD
Shigella Flexneri Disruption of Cellular Tension Promotes Intercellular Spread
Duncan-Lowey JK, Wiscovitch AL, Wood TE, Goldberg MB, Russo BC
Published in Cell Reports on November 24, 2020 | *Summary available


IMPROVING ADENOVIRUS IMMUNOTHERAPY IN GLIOBLASTOMA
Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma
Kiyokawa J, Kawamura Y, Ghouse SM, Acar S, Barcin E [et al.], Wakimoto H
Published in Clinical Cancer Research on November 30, 2020 | *Summary available

Publication Summaries

ANDROGEN RECEPTOR SIGNALING AND MELANOMA CELL GROWTH
Sustained Androgen Receptor Signaling Is a Determinant of Melanoma Cell Growth Potential and Tumorigenesis.
Ma M, Ghosh S, Tavernari D, Katarkar A, Clocchiatti A [et al.], Dotto GP
Published in Journal of Experimental Medicine on October 28, 2020

Melanoma is the fifth most common tumor in the world. As with many other types of cancer, women have a better outcome than men. Differential levels of male sex hormones—androgens—are one of the possible explanations. We reveal that removing the communication between these hormones and their receptors, by both genetic and pharmacological approaches, has a beneficial effect. Melanoma cells proliferation is hampered, and the immune system is activated to fight the tumor. The findings and the clinical perspectives they imply may be beneficial for all, including women, in whom androgen receptors are less active.

(Summary submitted by Gian Paolo Dotto, MD, PhD, Department of Dermatology, Cutaneous Biology Research Center)


GLUTEN CHALLENGE CLINICAL TRIAL
Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial
Leonard MM, Silvester JA, Leffler D, Fasano A, Kelly CP [et al.], Smithson G
Published in Gastroenterology on October 29, 2020

Celiac disease is an autoimmune condition triggered by gluten ingestion. Removing gluten from the diet leads to disease remission. Re-exposure results in disease return as shown by symptoms, small intestinal damage and activation of the immune response. In this double-blind, two-dose gluten trial, we assessed multiple biomarkers to supplement or replace histology; IL-2 was the earliest and most sensitive marker of gluten exposure. IL-2 levels and symptoms increased significantly at both gluten doses, and histology, video capsule endoscopy and other biomarkers showed significant changes only at the higher dose. These findings provide a foundation for the design of clinical trials.

(Summary submitted by Maureen Leonard, MD, MMSc, Center for Celiac Research and Treatment, Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children)


PLASMONIC SENSORS FOR EXTRACELLULAR VESICLE ANALYSIS
Plasmonic Sensors for Extracellular Vesicle Analysis: From Scientific Development to Translational Research
Chin LK, Son T, Hong JS, Liu AQ, Skog J, [et al.] Im H
Published in ACS Nano on October 29, 2020

Extracellular vesicles (EV) have emerged as new biomarkers of various diseases, such as cancers, neurodegenerative diseases and SARS-CoV-2 infection. For clinical translation, the main challenge is to develop sensitive and robust sensing technologies for EV analysis. Plasmonic sensors have been widely used for the label-free detection of target molecules captured by ligands immobilized on the surface, leveraging the enhanced signal intensity and sensitivity. We reviewed various plasmonic sensors developed for analyzing EVs in biofluids and compared their performances and clinical translational potential. We also discussed practical challenges in translating research development in laboratory settings to bedside clinical applications. Based on current research outcomes, plasmonic sensors are a promising technology for EV analysis in diagnosing various diseases.

(Summary submitted by Lip Ket Chin, PhD, Department of Radiology, Center for Systems Biology)


SINGLE-CELL PROFILING OF EBOLA VIRUS DISEASE
Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics
Kotliar D, Lin AE, Logue J, Hughes TK, Khoury NM [et al.], Bennett RS
Published in Cell on November 02, 2020

The overwhelming lethality of Ebola virus infection results in large part from a dysregulated and ineffective host immune response. To study this, we characterized the gene and protein expression of >100,000 circulating immune cells in a rhesus macaque model of Ebola infection. We directly sequence viral as well as host transcripts, allowing us to define the predominant infected cell population in circulation. Furthermore, we identify gene expression changes correlating with the viral life-cycle, demonstrating that Ebola represses antiviral pathways and upregulates pro-viral genes within infected cells. This work provides a framework for characterizing host-virus interactions under maximum containment.

(Summary submitted by Dylan Kotliar, PhD, Division of Infectious Diseases, Department of Medicine)


GENETIC CLUES FOR CROHN'S DISEASE
A Missense Variant in SLC39A8 Confers Risk for Crohn's Disease by Disrupting Manganese Homeostasis and Intestinal Barrier Integrity
Nakata T, Creasey EA, Kadoki M, Lin H, Selig MK [et al.], Xavier RJ
Published in PNAS on November 02, 2020

The missense A391T variant in the SLC39A8 gene is a risk allele for multiple conditions, including cardiovascular disease, schizophrenia, Parkinson's disease, and Crohn's disease (a form of inflammatory bowel disease, or IBD). We generated a SLC39A8 A391T mouse model to study how it impacts such a variety of tissues. The mice exhibited severe manganese deficiency in the colon associated with impaired intestinal barrier function, thus sensitizing the mice to intestinal inflammation. The findings suggest a tissue-specific mechanism by which this allele increases susceptibility to IBD and potentially other diseases.

(Summary submitted by Ramnik J. Xavier, MD, Digestive Healthcare Center, Division of Gastroenterology, Department of Molecular Biology, Center for Computational and Integrative Biology)


DELIRIUM IN OLDER PATIENTS WITH COVID-19
Delirium in Older Patients with COVID-19 Presenting to the Emergency Department
Kennedy M, Helfand BKI, Gou RY, Gartaganis SL, Webb M [et al], Inouye SK
Published in JAMA Network Open on November 02, 2020

Delirium is a serious medical condition where there is a sudden change in someone's cognition or thinking. The symptoms of delirium are varied and may include new agitation, sleepiness, memory problems, or hallucinations. This study included patients 65 years of age and older diagnosed with COVID-19 in the emergency department. We found that 28% of patients had delirium and one-third of delirious patients lacked common COVID-19 symptoms like fever and shortness of breath. Patients with delirium had worse outcomes including in-hospital death. This study highlights that delirium is an important symptom of COVID-19 infection and new delirium should prompt testing for COVID-19.

(Summary submitted by Maura Kennedy, MD, Department of Emergency Medicine)


LIVER CANCER IN PATIENTS WITH HEPATITIS C
Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients with Hepatitis C in the Era of Direct-Acting Antiviral Agents.
Chen Q, Ayer T, Adee MG, Wang X, Kanwal F, Chhatwal J
Published in JAMA Network Open on November 02, 2020

The new hepatitis C treatments offer a cure but many individuals, even after cure, would remain at risk of developing hepatocellular carcinoma (HCC), the most common type of liver cancer. The main implication of our study is that the future incidence and burden of HCC will shift to these individuals who achieved cured from hepatitis C. For instance, the proportion of incident HCC cases that occur in individuals with virologically cured hepatitis C will increase from 5% in 2012 to 46% in 2040. We need appropriate screening guidelines for hepatitis C individuals to detect HCC in early stages, when it can be treated. The number of people needing biannual screening will also increase from 106,000 in 2012 to 640,000 in 2030. Second, the average age of HCC patients will increase and many patients may not be eligible for liver transplantation.

(Summary submitted by Jagpreet Chhatwal, PhD, MGH Institute for Technology Assessment)


GOUT PREVENTION THROUGH WEIGHT LOSS
Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors
McCormick N, Rai SK, Lu N, Yokose C, Curhan GC, Choi HK
Published in JAMA Open Network on November 02, 2020

Gout is a very painful form of inflammatory arthritis affecting about 9 million U.S. adults, more often men. Its frequency and burden are growing worldwide, alongside obesity rates. Using data from >44,000 US men followed for 26 years in the Health Professionals Follow-Up Study (based at Harvard T.H. Chan School of Public Health), we found that most new gout cases (77%) could have been prevented by keeping a healthy lifestyle: having a normal body weight, following a healthy (DASH-style) diet, and avoiding alcohol and diuretics. Among obese men, weight loss was essential for preventing gout. Adopting healthier lifestyles could substantially prevent this disabling condition.

(Summary submitted by Natalie McCormick, PhD, Division of Rheumatology, Allergy and Immunology, Department of Medicine)


DIABETES DRUG MAY REDUCE RISK OF CARDIAC EVENTS
Effects of Canagliflozin on Amino-Terminal Pro-B-Type Natriuretic Peptide: Implications for Cardiovascular Risk Reduction
Januzzi JL Jr, Xu J, Li J, Shaw W, Oh R [et al.], Hansen MK
Published in Journal of the American College of Cardiology on November 03, 2020

Sodium glucose cotransporter-2 (SGLT2) inhibitors are drugs to treat diabetes mellitus, but recent studies have shown these drugs also reduce risk for cardiac events including heart failure. N-terminal pro-B type natriuretic peptide (NT-proBNP) is a blood test that predicts risk for cardiac events including heart failure. In our study, a high percentage of patients with diabetes had abnormal baseline NT-proBNP, indicating higher risk for future cardiac events. Treatment with the SGLT2 inhibitor canagliflozin improved NT-proBNP and reduced cardiac events. These results suggest NT-proBNP predicts risk in patients with diabetes and its changes may reflect cardiac benefit of SGLT2 inhibitors.

(Summary submitted by James L. Januzzi, MD, Division of Cardiology, Department of Medicine)


PREMATURE MENOPAUSE MAY BE IMPORTANT RISK FACTOR FOR AAA
Association of Premature Menopause with Risk of Abdominal Aortic Aneurysm in the Women's Health Initiative
Chou EL, Pettinger M, Haring B, Allison MA, Mell MW [et al.], Liu S
Published in Annals of Surgery on November 04, 2020

Abdominal aortic aneurysms (AAA) are common and typically asymptomatic until complications or rupture occurs. Indications for screening and timing of elective repair are largely based on risk factors identified from male populations. Although AAAs are approximately three times more common in men, women account for almost half of AAA-related deaths and bear a proportionally greater burden of AAA-associated morbidity and mortality. Our study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the vascular care of women.

(Summary submitted by Elizabeth L. Chou, MD, Division of Vascular and Endovascular Surgery, Department of Surgery)


BACTERIAL-HOST INTERFACE IN ENDOCARDITIS
Multimodal Imaging of Bacterial-Host Interface in Mice and Piglets with Staphylococcus Aureus Endocarditis
Panizzi P, Krohn-Grimberghe M, Keliher E, Ye YX, Grune J [et al.], Nahrendorf M
Published in Science Translational Medicine on November 04, 2020

Endocarditis is a difficult to manage and lethal infection of the heart valves. Even antibiotics often cannot kill the bacteria that form colonies inside the heart because the bacteria hijack the host's clotting system to build a protective barrier. We co-developed therapeutics and multimodal molecular imaging targeting these so-called virulence factors, specifically a family of optical and PET imaging reporters binding to the wall around bacterial colonies in mice and pigs. We employed imaging to monitor therapy with antibodies neutralizing virulence factors in mice with endocarditis. This treatment deactivated bacterial defenses against innate immune cells, decreased imaging signal and improved survival.

(Summary submitted by Matthias Nahrendorf MD, PhD, Division of Cardiology, Department of Medicine, Department of Radiology, Center for Systems Biology)


PREMATURE MENOPAUSE, CHIP AND CVD RISK
Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women
Honigberg MC, Zekavat SM, Niroula A, Griffin GK, Bick AG [et al.], Natarajan P
Published in Circulation on November 09, 2020 | Press Release

Premature age of menopause (before age 40) is a risk factor for coronary heart disease in women, but how premature menopause predisposes to heart disease is unclear. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized, asymptomatic condition where blood precursor cells acquire mutations in genes associated with development of blood cancer. Somewhat surprisingly, CHIP is also linked to accelerated development of heart disease. In two large cohorts of women, we found women with premature menopause were enriched for CHIP by 1.4-fold and those with natural (i.e., spontaneous) premature menopause by 1.7-fold. In turn, CHIP independently predicted coronary heart disease events. Our findings imply natural premature menopause may signal predisposition to develop CHIP and CHIP-associated cardiovascular disease.

(Summary submitted by Michael Honigberg, MD, MPP, Division of Cardiology, Department of Medicine)


COUNTRY PREPAREDNESS AND QUALITY OF CLINICAL CARE FOR CVD
Association Between Country Preparedness Indicators and Quality Clinical Care for Cardiovascular Disease Risk Factors in 44 Lower- and Middle-income Countries: A Multicountry Analysis of Survey Data
Davies JI, Reddiar SK, Hirschhorn LR, Ebert C, Marcus ME [et al.], Jaacks LM
Published in PLOS Medicine on November 10, 2020

Cardiovascular risk factors (CVDRFs) such as high blood pressure and diabetes are approaching epidemic levels in many low and middle-income countries (LMICs), and without treatment patients are vulnerable to heart attack, stroke and death. In this analysis, our research team measured whether individuals with high blood pressure or diabetes in LMICs had their condition diagnosed, treated or controlled. We then evaluated whether these clinical care outcomes were associated with current proxy indicators used by WHO. We found that these indicators are generally poor proxies for quality clinical care received by patients for CVDRFs in LMICs. Future policy should be based on direct measurement of quality clinical care instead of current indicators.

(Summary submitted by Jennifer Manne-Goehler, MD, ScD, Division of Infectious Diseases, Department of Medicine)


PATIENT OUTCOMES AND TREATMENT RESPONSE IN GASTROINTESTINAL CANCER
Associations of Baseline Patient?reported Outcomes with Treatment Outcomes in Advanced Gastrointestinal Cancer
van Seventer EE, Fish MG, Fosbenner K, Kanter K, Mojtahed A [et al.], Nipp RD
Published in Cancer on November 10, 2020

In this prospective cohort study, we enrolled patients with advanced gastrointestinal cancer who were initiating a new line of chemotherapy and asked them to report their quality of life and symptom burden at the time of starting treatment. We found that baseline patient-reported outcomes (PROs) were associated with subsequent treatment response. We found that greater physical symptoms and lower functional quality of life scores at baseline were associated with progressive disease as well as increased health care utilization and worse survival outcomes. Our findings further support the association of PROs with important clinical outcomes, including the novel finding of treatment response.

(Summary submitted by Emily van Seventer, MPH, Division of Hematology and Oncology, Department of Medicine, Mass General Cancer Center)


TFEB LOCALIZATION- AND STIMULUS-SPECIFIC RESPONSES
TFEB Transcriptional Responses Reveal Negative Feedback by BHLHE40 and BHLHE41
Carey KL, Paulus GLC, Wang L, Balce DR, Luo JW [et al.], Xavier RJ
Published in Cell Reports on November 10, 2020

The transcription factor TFEB acts as a sensor and signal for the cell to produce lysosomes, which help cells recycle old or unneeded cellular components and ingested pathogens. Because breakdowns in TFEB and lysosome function are linked to metabolic, neurological, and infectious diseases, we set out to identify all of the cellular circuits TFEB directs. We found that TFEB's transcriptional impacts depend heavily on its location within the cell, as well as its stimulation state, and that its influence is held in check by the genes BHLHE40 and BHLHE41.

Summary submitted by Ramnik J. Xavier, MD, Digestive Healthcare Center, Division of Gastroenterology, Department of Molecular Biology, Center for Computational and Integrative Biology)


INSURANCE EXPANSION MAY REDUCE UTILIZATION OF EMERGENCY MEDICAL SERVICES
Association of Affordable Care Act Implementation with Ambulance Utilization for Asthma Emergencies in New York City, 2008-2018
Peters GA, Ordoobadi AJ, Cash RE, Wong ML, Avillach P, Camargo, CA Jr.
Published in JAMA Network Open on November 11, 2020 | Press Release

Ambulatory care-sensitive conditions are chronic diseases that can result in medical emergencies if not properly controlled through outpatient care. In this study, we tracked uninsured rates and ambulance calls for asthma, a common ambulatory care-sensitive condition, in each ZIP code throughout New York City during 2008-2018. We found that asthma emergencies significantly decreased after the Affordable Care Act (also known as Obamacare) was implemented in 2014, and that neighborhoods with greater increases in health insurance coverage under Obamacare tended to have greater decreases in asthma emergencies. These findings suggest that people with improved access to health care under Obamacare required fewer 911 calls for asthma emergencies, likely due to better outpatient control of their asthma.

(Summary submitted by Gregory Peters, MD, Department of Emergency Medicine)


SIMULATING OUTCOMES OF COVID-19 PUBLIC HEALTH STRATEGIES IN SOUTH AFRICA
Cost-effectiveness of Public Health Strategies for COVID-19 Epidemic Control in South Africa: A Microsimulation Modelling Study
Reddy KP, Shebl FM, Foote JHA, Harling G, Scott JA [et al.], Siedner MJ
Published in Lancet Global Health on November 11, 2020 | Press Release

Identifying cost-effective public health interventions is essential to control COVID-19 in resource-constrained settings. We developed a microsimulation model to project the clinical and economic outcomes of various combinations of non-pharmaceutical public health interventions for COVID-19 in South Africa. We found that a combination of community-based contact tracing, isolation of confirmed cases, mass symptom screening, and quarantine of close contacts reduced infections, hospitalizations and deaths while being cost-effective compared with testing at health care centers alone. Our results demonstrate that a multi-pronged strategy offers good value and should be considered by policy makers to prevent infections and save lives in resource-constrained settings.

(Summary submitted by Krishna Reddy, MD, MS, and Mark Siedner, MD, MPH, Medical Practice Evaluation Center, Mongan Institute, Department of Medicine)


BREAST CANCER TUMOR FORMATION AND THERAPY
Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.
Krug K, Jaehnig EJ, Satpathy S, Blumenberg L, Karpova A [et al.], Gillette MA
Published in Cell on November 16, 2020

Breast cancer is a very diverse disease, making it challenging for doctors and scientists to tailor promising treatment combinations for patients. Working with the National Cancer Institute's Clinical Proteomics Tumor Analysis Consortium (CPTAC), we conducted comprehensive integrated proteomic and genomicor "proteogenomic"profiling of a large set of breast tumors. Our findings highlight revised tumor subtypes, metabolic vulnerabilities, immunotherapy and targeted therapeutic opportunities and more, and suggest a role for proteogenomics in cancer diagnosis and treatment planning.

(Summary submitted by Michael Gillette, MD, PhD, Division of Pulmonary and Critical Care Medicine, Department of Medicine)


PATIENT TRUST IN THE SURGICAL DECISION SCALE
Validation of the Trust in the Surgical Decision Scale
Brodney S, Sepucha K, Fowler FJ Jr, Valentine KD, Barry MJ
Published in Annals of Surgery on November 16, 2020

Trusting relationships are being increasingly recognized as important attributes of excellent health care. Our goal was to develop a measure of a patient's trust in their surgeon to keep them informed and involved in surgical decision-making. A 14-item scale was tested in a web-sample of 300 people who had orthopedic surgery within two years. We found a five-item subset of the 14 original items was similarly reliable and valid (e.g. more trust was related to more shared decision making and less regret). We concluded that this five-item scale can be used to measure a patient's trust in their surgeon.

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


TRAPPC9 DEFICIENCY IMPAIRS LEARNING AND MEMORY
Trappc9 Deficiency in Mice Impairs Learning and Memory by Causing Imbalance of Dopamine D1 and D2 Neurons
Ke Y, Weng M, Chhetri G, Usman M, Li Y [et al.], Li X
Published in Science Advances on November 18, 2020

This study stemmed from our previous finding that the causative mutation of Huntington's disease compromises a factor for turning on RAB11. In looking for this factor, we discovered transport protein particle complex 9 (trappc9), which has been implicated in intellectual disability, autism spectrum disorder, schizophrenia and attention-deficit hyperactivity disease. We generated trappc9-deficient mice, which recapitulated features of patients bearing trappc9 mutations. We further found that trappc9 deficiency specifically disturbed RAB11 and altered the balance of dopamine D1 and D2 neurons and showed that drugs acting on dopamine receptors were effective in improving brain functions of trappc9-deficient mice. Our studies suggest a pathogenic mechanism and a potential therapy for disorders linked to trappc9.

(Summary submitted by Xueyi Li, PhD, Department of Neurology)


A NOVEL PORTABLE MRI SCANNER
A Portable Scanner for Magnetic Resonance Imaging of the Brain
Cooley CZ, McDaniel PC, Stockmann JP, Srinivas SA, Cauley SF [et al.], Wald LL
Published in Nature Biomedical Engineering on November 23, 2020 | Press Release

MRI is a powerful brain imaging tool that allows us to see more than other imaging modalities. Unfortunately, the MRI scanner's size and cost limit its use, especially when it is unsafe or infeasible to transport a patient to a scanner site. To address this, we developed a portable, low-cost MRI brain scanner to bring imaging to the patient, wherever they may be. The scanner uses a new image encoding method that makes it nearly silent and requires much less power than conventional MRI. It uses a new type of lightweight head-sized magnet (22" x 19") that operates with a lower magnetic field, making it both safe and easy to transport the scanner to the patient.

(Summary submitted by Clarissa Zimmerman Cooley, PhD, Martinos Center, Department of Radiology)


INTERCELLULAR SHIGELLA SPREAD
Shigella Flexneri Disruption of Cellular Tension Promotes Intercellular Spread
Duncan-Lowey JK, Wiscovitch AL, Wood TE, Goldberg MB, Russo BC
Published in Cell Reports on November 24, 2020

Our laboratory studies the molecular mechanisms by which infectious agents manipulate human hosts in ways that enhance disease. Here, we demonstrate that the bacterial pathogen Shigella, the most common cause of diarrhea and dysentery worldwide, remodels the molecular frame of the host cell—the cytoskeleton—in previously unknown ways. Key to the Shigella infectious process is the spread of the organism from one infected human cell into adjacent cells. We show that to enable spread between cells, a Shigella decreases the tension of the cell's membrane by disrupting the cytoskeleton just beneath the cell surface, indicating that Shigella manipulates the biophysical properties of cells in ways that promote infection.

(Summary submitted by Marcia Goldberg, MD, Division of Infectious Diseases, Department of Medicine)


IMPROVING ADENOVIRUS IMMUNOTHERAPY IN GLIOBASTOMA
Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma
Kiyokawa J, Kawamura Y, Ghouse SM, Acar S, Barcin E [et al.], Wakimoto H
Published in Clinical Cancer Research on November 30, 2020

Malignant brain tumor glioblastoma abundantly contains hyaluronan, a high molecular weight sugar-like molecule, in the space outside the cells. Hyaluronan promotes tumor cell migration and resistance to therapies, but its role in the regulation of tumor-fighting immunity is unknown. We show that treatment with genetically engineered cancer killer adenovirus that carries a gene coding for hyaluronidase capable of degrading hyaluronan enhanced the recruitment of T lymphocytes and macrophages in glioblastoma in the mouse brain compared with a control virus without hyaluronidase. Combination of the hyaluronidase-expressing virus and immune checkpoint inhibitor extended animal survival, nominating a promising immunotherapy for clinical translation.

(Summary submitted by Hiroaki Wakimoto, MD, PhD, Department of Neurosurgery)

Press Releases

Brain Injury Survivors and Their Caregivers Can Benefit from a Resiliency Program
Featuring Jonathan Rosand, MD, MSc, and Ana-Maria Vranceanu, PhD

An early resiliency intervention program for survivors of acute brain injury and their caregivers has shown clinically significant improvement in emotional distress, according to a recent study.


Editorial: New Research Strengthens the Case for E-cigarettes as Smoking Cessation Aids, but More Evidence Is Needed
Featuring Nancy Rigotti, MD

New research shows that electronic cigarettes (e-cigarettes) can help smokers quit smoking cigarettes, according to an editorial in JAMA.


Study Reveals How Premature Menopause Increases Risk of Cardiovascular Disease
Featuring Michael Honigberg, MD, MPP and Pradeep Natarajan, MD, MMSc

Menopause that occurs before a woman is 40 years old accelerates aging and is a risk factor for cardiovascular disease.


Not All Patients with Certain Type of Heart Attack Receive the Same Care
Featuring Jason Wasfy, MD, MPhil

There are several different types of heart attacks, which occur when blood flow to the heart is blocked or reduced. New research reveals considerable uncertainty in how to care for patients with one type.


EMS Dispatches for Asthma Greatly Reduced After Expanded Access to Health Insurance
Featuring Gregory Peters, MD

The expansion of health insurance in New York City under the Affordable Care Act (ACA) resulted in a significant reduction in the dispatch of ambulances for asthma emergencies, a study by Mass General researchers has found.


The Final Stage: Antibody Evolution May Predict COVID-19 Outcomes
Featuring Galit Alter, PhD

For COVID-19, the difference between surviving and not surviving severe disease may be due to the quality, not the quantity, of the patients' antibody development and response, suggests a new Cell paper published by Galit Alter, PhD.


Study Reveals a Cost-effective Program of Health Interventions Against COVID-19 in Resource-challenged Countries
Featuring Krishna Reddy, MD, and Mark Siedner, MD, MPH

Researchers find that a public health strategy that combines contact tracing and community-based screening with isolation and quarantine centers can substantially reduce infections, hospitalizations and deaths from COVID-19 while being cost-effective in low-and-middle-income countries like South Africa.


Bursts of Exercise Can Lead to Significant Improvements in Indicators of Metabolic Health
Featuring Gregory Lewis, MD, and Ravi Shah, MD

Researchers find short bursts of physical exercise induce changes in the body's levels of metabolites that correlate to, and may help gauge, an individual's cardiometabolic, cardiovascular and long-term health.


In South Africa, Enlisting Local Leaders in Combating a Second Covid-19 Surge
Featuring Krista Dong, MD

!n South Africa's KwaZulu-Natal province, a program of the Ragon Institute of MGH, MIT and Harvard is enlisting leadership within rural communities to counter a second wave of the COVID-19 pandemic.


Potential Cholera Vaccine Target Discovered
Featuring Edward Ryan, MD

Findings from a Mass General-led team may help scientists develop a more effective vaccine for cholera, a bacterial disease that causes severe diarrhea and dehydration and is usually spread through contaminated water.


Early Details of Brain Damage in COVID-19 Patients
Featuring Otto Rapalino, MD

One of the first spectroscopic imaging-based studies of neurological injury in COVID-19 patients has been reported by researchers in the American Journal of Neuroradiology.


Early Treatment with Lorlatinib Improves Survival and Prevents Disease Progression in Some Lung Cancer Patients
Featuring Justin Gainor, MD, and Alice Shaw, MD, PhD

Lung cancer patients with a specific genetic alteration lived longer and were protected against metastasis to the brain when treated early with the drug lorlatinib (Lorbrena), according to a study led by researchers at Mass General, published in the New England Journal of Medicine.


Effectiveness of COVID-19 Vaccines Will Be Heavily Influenced by Infrastructure, as Well as Public Attitudes and Behaviors
Featuring Rochelle Walensky, MD, MPH

The success of a COVID-19 vaccine will depend not only on its efficacy, but also on how fast and widely it can be delivered, the severity of the pandemic, and the public's willingness to be immunized, according to a study published in Health Affairs.


Researchers Develop Low-cost, Portable Brain Imaging Scanner
Featuring Clarissa Zimmerman Cooley, PhD

A team of investigators has developed a low-cost, compact, portable and low-power "head only" MRI scanner that could be mounted in an ambulance, wheeled into a patient's room or put in small clinics or doctors' offices around the world.


Emergency Department Doctors Ask: “Where Did All the Patients Go?”
Featuring David Brown, MD, Sayon Dutta, MD, MPH, Ali Raja, MD, MBA, MPH, Ben White, MD, and Brian Yun, MD, MBA, MPH

During the early days of the COVID-19 pandemic in New England, emergency department visits for medical emergencies—including psychiatric problems, trauma and heart attacks—declined by nearly a third, raising concerns among clinicians that critically ill patients were not seeking the care they needed for fear of coronavirus infection.


Genetic Treatment Plus Exercise Reverses Fatigue in Mice With Muscle Wasting Disease
Featuring Thurman Wheeler, MD

Adding exercise to a genetic treatment for myotonic dystrophy type 1 (DM1) was more effective at reversing fatigue than administering the treatment alone in a study using a mouse model of the disease. In fact, exercise alone provided some benefit whereas the genetic treatment alone did not.


Combination Therapy Might Improve Outcomes in Treatment-resistant Liver Cancer
Featuring Dan G. Duda, DMD, PhD

A combination cancer therapy that is effective against treatment-resistant hepatocellular carcinoma (HCC) by inhibiting tumor growth and may increase survival has been identified.


Blog Posts

Vitamin D Levels Could Help Identify Patients at Risk of Increased Opioid Use After Surgery
Featuring Yuhree Kim, MD, MPH, and Maryam Asgari, MD, MPH

Opioids can be an effective painkiller following major surgery but prescribing them is not without risk. Mass General researchers recently found a compelling connection between vitamin D levels in the blood taken at the time of surgery and the risk of using opioids at higher doses, for longer periods of time, and for developing an opioid use disorder.


2020 MGRI Image Contest: Meet the Winner and Finalists

The MGRI Image Contest was created in 2018 with the goal of providing and inside look at Mass General research and sharing the stories of our researchers.


How Developing More Accessible Patient Education Tools Could Reduce Disparities in Breast Cancer Screening and Care
Featuring Randy C. Miles, MD, MPH, and Constance Lehman, MD, PhD

Research has shown that 80% of internet users look for health-related information on the web. However, the ability to understand this material depends on each patient's health literacy—the ability to process and understand basic health information.


Feeling Pandemic Stress? How Mindfulness Techniques and These Brain-Friendly Habits Can Help
Featuring Rudy Tanzi, PhD

Studies have shown COVID-19 has increased clinician burnout, and that rates of stress, anxiety and depression have increased. With this in mind, the Center for Faculty Development at Mass General recently held a seminar on mindfulness led by Rudy Tanzi, PhD.


58 Mass General Investigators Named Highly Cited Researchers of 2020

Clarivate Analytics' Web of Science Group recently released their annual list of Highly Cited Researchers, and we are pleased to announce that 58 investigators from the Mass General Research Institute made the list.


Make Your Message Stick: Tips for Research Communication and Outreach from Dr. Renee Salas
Featuring Renee Salas, MD, MPH, MS

The playwright George Bernard Shaw once said, "The single biggest problem in communication is the illusion that it has taken place." The same problem often applies to communicating your research findings, says Renee Salas, MD, MPH, MS.


COVID-19 and the Holidays: Tips on How to Celebrate Safely

While we may not be able to hold our loved ones as close as we'd like during this year's holiday season, it is still possible to stay connected and celebrate safely. In a recent article, Amir Mohareb, MD, and Kristen Hysell, MD, MPH, of the Infectious Diseases Division at Mass General, discuss steps that you can take to make this season joyful and safe.