Two-Part Priming Strategy to Increase the Sensitivity of Liquid Biopsies
Priming Agents Transiently Reduce the Clearance of Cell-free DNA to Improve Liquid Biopsies
Martin-Alonso C, Tabrizi S, Xiong K, Blewett T, Sridhar S [et al.], Adalsteinsson VA
Published in Science on 1/19/2024 | *Summary available | Research Spotlight 

Benzodiazepines Associated with Worse Disease Progression in Progressive Supranuclear Palsy
Concomitant Medications for Progressive Supranuclear Palsy: A Secondary Analysis of a Randomized Clinical Trial
Iyer JM, Gunzler D, Lang AE, Golbe LI [et al.], Wills AM; AL-108-231 Study Group
Published in JAMA Neurology on 1/22/2024 | *Summary available | Research Spotlight 

High School Students Who Report Using Alcohol, Cannabis or Nicotine at Higher Risk for Suicidal Thoughts and Other Mental Health Disorders
Substance Use, Suicidal Thoughts, and Psychiatric Comorbidities Among High School Students
Tervo-Clemmens B, Gilman JM, Evins AE, Bentley KH, Nock MK, Smoller JW, Schuster RM
Published in JAMA Pediatrics on 1/29/2024 | *Summary available  

Vaccinated Toddlers Obtaint a Functional Antibody Response Equally Strong as Adults
Humoral Profiles of Toddlers and Young Children Following SARS-CoV-2 mRNA Vaccination
Nziza N, Deng Y, Wood L, Dhanoa N, Dulit-Greenberg N [et al.], Yonker LM
Published in Nature Communications on 1/30/2024 

Discovery of Neurons in the Human Brain Able to Predict What We're Going to Say Before We Say It
Single-neuronal Elements of Speech Production in Humans
Khanna AR, Muñoz W, Kim YJ, Kfir Y, Paulk AC [et al.], Williams ZM
Published in Nature on 1/31/2024 | *Summary available | Press Release 

Liso-cel Demonstrated Durable Remissions and a Manageable Safety Profile at 2-year Follow-up in Lymphoma Patients
Two-year Follow-up of Lisocabtagene Maraleucel in Relapsed or Refractory Large B-cell Lymphoma in TRANSCEND NHL 001
Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M [et al.], Siddiqi T.
Published in Blood on 2/1/2024 | Press Release 

First Comparative Analysis of Gut Microbiome of People with HIV Living in the U.S. And Sub-saharan Africa
HIV-associated Gut Microbial Alterations Are Dependent on Host and Geographic Context
Rocafort M, Gootenberg DB, Luévano JM Jr, Paer JM, Hayward MR [et al.], Kwon DS
Published in Nature Communications on 2/5/2024 | *Summary available 

Resilience Training as Tool for Addressing and Reducing Loneliness among At-risk Young Adults
A Brief Resilience-Enhancing Intervention and Loneliness in At-Risk Young Adults: A Secondary Analysis of a Randomized Clinical Trial
DeTore NR, Burke A, Nyer M, Holt DJ
Published in JAMA Network Open on 2/5/2024 | *Summary available 

When Police Kill Unarmed Black People, Other Black People in the General U.S. Population Experience Worse Sleep
Officer-Involved Killings of Unarmed Black People and Racial Disparities in Sleep Health
Venkataramani AS, Bair EF, Bor J, Jackson CL, Kawachi I [et al.], Tsai AC
Published in JAMA Internal Medicine on 2/5/2024 | *Summary available 

Targeted Approach for Gout Flare Prevention
Serum Urate and Recurrent Gout
McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK
Published in JAMA on 2/6/2024 | *Summary available 

Moderate Dose of Multivitamin Supplements after a Diagnosis of Nonmetastatic Colorectal Cancer Associated with Lower Mortality
Post-diagnostic Multivitamin Supplement Use and Colorectal Cancer Survival: A Prospective Cohort Study
He MM, Wang K, Lo CH, Zhang Y, Polychronidis G [et al.], Song M
Published in Cancer on 2/6/2024 | *Summary available 

Stigmatizing Language on Liver Transplant Center Websites May Discourage Patients from Seeking Treatment
Stigmatizing Language for Alcohol Use Disorder and Liver Disease on Liver Transplant Center Websites
Mahle R, Okanlawon A, Luther J, Louissaint J, Zhang W
Published in JAMA Network Open on 2/8/2024 | *Summary available | Press Release 

Coaxing Macrophages to Fight Cancer
Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype
Enbergs N, Halabi EA, Goubet AG, Schleyer K, Fredrich IR [et al.], Weissleder R
Published in Advanced Science on 2/11/2024 | *Summary available 

Hippocampus Is Essential for Offline Motor Learning
Maintenance of Procedural Motor Memory Across Brief Rest Periods Requires the Hippocampus
Mylonas D, Schapiro AC, Verfaellie M, Baxter B, Vangel M, Stickgold R, Manoach DS
Published in Journal of Neuroscience on 2/13/2024 | *Summary available 

New Insights into Cysteine Metabolism and Hypoxia
Hypoxia-inducible Factor Induces Cysteine Dioxygenase and Promotes Cysteine Homeostasis in Caenorhabditis elegans
Warnhoff K, Bhattacharya S, Snoozy J, Breen PC, Ruvkun G
Published in eLife on 2/13/2024 

Maternal PFOS Concentration Associated with a Higher Risk of Low Birthweight
Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes
Zhang Y, Mustieles V, Martin L, Sun Y, Hillcoat A [et al.], Messerlian C
Published in Environmental Science & Technology on 2/13/2024 

Post–COVID-19 Condition Associated with Depressive Symptoms and Functional Impairment
Cognitive Symptoms of Post-COVID-19 Condition and Daily Functioning
Jaywant A, Gunning FM, Oberlin LE, Santillana M, Ognyanova K [et al.], Perlis RH
Published in JAMA Network Open on 2/14/2024 

Development of Alternative Therapeutic to High Dose IVIG
An Engineered Immunomodulatory IgG1 Fc Suppresses Autoimmune Inflammation through Pathways Shared with I.V. Immunoglobulin
Sneed SL, Reese BB, Laureano AF, Ratnapriya S, Fraschilla I [et al.], Anthony RM
Published in Journal of Clinical Investigation on 2/15/2024 | *Summary available 

Clonal Hematopoiesis and Atrial Fibrillation
Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation
Lin AE, Bapat AC, Xiao L, Niroula A, Ye J [et al.], Ebert BL
Published in Circulation on 2/15/2024 | *Summary available 

Greater Social Activity Can Provide Resilience Against Alzheimer’s Disease Pathology and Cognitive Decline
Social Activity Mediates Locus Coeruleus Tangle-related Cognition in Older Adults
Zide BS, Donovan NJ, Lee S, Nag S, Bennett DA, Jacobs HIL
Published in Molecular Psychiatry on 2/15/2024 | *Summary available 

Gene Discovered Significantly Associated with Decreased Lung Cancer Risk among Smokers
CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility
Du M, Xin J, Zheng R, Yuan Q, Wang Z [et al.], Christiani DC
Published in Cancer Research on 2/15/2024 | *Summary available 

Promising Results Suggest That the Human Immune System Can Be Programmed to Engage and Target Residual HIV-infected Cells
Selection of Epigenetically Privileged HIV-1 Proviruses during Treatment with Panobinostat and Interferon-α2a
Armani-Tourret M, Gao C, Hartana CA, Sun W, Carrere L [et al.], Lichterfeld M
Published in Cell on 2/16/2024 | *Summary available 

Genomic Study to Improve Prediction of Type 2 Diabetes
Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology
Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X [et al.], Zeggini E
Published in Nature on 2/19/2024 | *Summary available 

Private Equity Investment Within Surgical Specialties Created Increased Practice Consolidation
Private Equity Investment in Surgical Care
Sievers MT, Neevel A, Diaz A, Rouanet E, Sheetz K [et al.], Chhabra KR
Published in Annals of Surgery on 2/19/2024 | *Summary available 

Patients Achieving Surgical Remission of Cushing’s Disease Have Higher Incidence of Autoimmune Disease
Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study
Nyanyo DD, Mikamoto M, Galbiati F, Remba-Shapiro I, Bode K [et al.], Nachtigall LB
Published in Annals of Internal Medicine on 2/20/2024 | *Summary available 

Substudy of REPRIEVE Trial Reveals How Statin Therapy Prevents Cardiovascular Disease in People with HIV
Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial
Lu MT, Ribaudo H, Foldyna B, Zanni MV [et al.], Grinspoon SK; REPRIEVE Trial Writing Group
Published in JAMA Cardiology on 2/21/2024 | *Summary available | Press Release 

Birth Month Associated with Timing of Vaccination Through Timing of Preventive Care Visits
Optimal Timing of Influenza Vaccination in Young Children: Population Based Cohort Study
Worsham CM, Bray CF, Jena AB
Published in BMJ on 2/21/2024 

Mouse Model Recapitulates Patient Symptoms and Provides Robust Cellular and Molecular Benchmarks for Therapeutic Testing
Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction
Deehan MA, Kothuis JM, Sapp E, Chase K, Ke Y [et al.], DiFiglia M
Published in Journal of Neuroscience on 2/22/2024 | *Summary available 

Potentially Defining a Therapeutic Window for Gene Therapy for Rett, CDKL5-, and Fragile-X Syndromes
Variable Expression of MECP2, CDKL5, and FMR1 in the Human Brain: Implications for Gene Restorative Therapies
Zito A, Lee JT
Published in PNAS on 2/22/2024 

CAR-TEAM Cells Enable Modification of Tumor Stroma, Leading to Increased Elimination of PDAC Tumors
Mesothelin CAR T-cells Secreting anti-FAP/anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and Its Stroma
Wehrli M, Guinn S, Birocchi F, Kuo A, Sun Y [et al.], Maus MV
Published in Clinical Cancer Research on 2/23/2024 | *Summary available 

New Nanoparticle Platform Can Act as a Local Drug Depot with Spatiotemporally Controlled Release of Cancer Therapeutics
Sustained and Localized Drug Depot Release using Radiation-Activated Scintillating Nanoparticles
Kang M, Quintana J, Hu H, Teixeira VC, Olberg S [et al.], Miller MA
Published in Advanced Materials on 2/23/2024 

Two-Part Priming Strategy to Increase the Sensitivity of Liquid Biopsies
Priming Agents Transiently Reduce the Clearance of Cell-free DNA to Improve Liquid Biopsies
Martin-Alonso C, Tabrizi S, Xiong K, Blewett T, Sridhar S [et al.], Adalsteinsson VA
Published in Science on 1/19/2024 | Research Spotlight 

Liquid biopsies, such as detection of circulating tumor DNA (ctDNA) in plasma, can help us detect cancer in the body earlier, when it is easier to treat. But current technologies do not have high enough sensitivity: ctDNA tests are often negative, even when there are low levels of cancer in the body. This limitation is because blood samples often have very little to no ctDNA for many cancer patients. We have developed new methods, using nanoparticles and engineered antibodies, to increase how much ctDNA is collected in a blood draw by inhibiting the clearance of ctDNA from the body. In mice with tumors, our approach led to recovery of over ten-times more ctDNA in a blood sample and significantly improved the sensitivity of ctDNA tests for detecting very low levels of ctDNA. Our approach still needs to be tested in humans, but has the potential to significantly improve the performance of liquid biopsy tests for patients. 

(Summary submitted by Shervin Tabrizi, MD, Mass General Cancer Center) 

Benzodiazepines Associated with Worse Disease Progression in Progressive Supranuclear Palsy
Concomitant Medications for Progressive Supranuclear Palsy: A Secondary Analysis of a Randomized Clinical Trial
Iyer JM, Gunzler D, Lang AE, Golbe LI [et al.], Wills AM; AL-108-231 Study Group
Published in JAMA Neurology on 1/22/2024 | Research Spotlight 

PSP is a rare and devastating disease without any FDA approved treatments. Congresswoman Jennifer Wexton from Virginia recently announced that she has PSP. Jay Iyer, an undergraduate at Harvard, whose grandfather died from PSP, approached me while he was a freshman to ask how he could research PSP. I suggested that we look for medications that could slow down the progression of PSP in prior clinical trial databases. Instead, we found that benzodiazepines (such as lorazepam, clonazepam) seem to be associated with a faster (worse) disease progression. We would recommend against the use of these medications for people with PSP. 

(Summary submitted by Anne-Marie Wills, MD, MPH, Department of Neurology) 

High School Students Who Report Using Alcohol, Cannabis or Nicotine at Higher Risk for Suicidal Thoughts and Other Mental Health Disorders
Substance Use, Suicidal Thoughts, and Psychiatric Comorbidities Among High School Students
Tervo-Clemmens B, Gilman JM, Evins AE, Bentley KH, Nock MK, Smoller JW, Schuster RM
Published in JAMA Pediatrics on 1/29/2024 

This study reports on a survey of over 15,000 high school students across Massachusetts with the goal of understanding the relationship between substance use and other mental health symptoms in youth. Thoughts of suicide, feelings of depression and anxiety, psychotic-like experiences, and symptoms of inattention and hyperactivity were all more common among teens with more frequent use of cannabis, alcohol, and nicotine. Schools and providers should be aware that substance use often does not occur in a vacuum -- teens who use, particularly those who use often, are likely to present with multiple other mental health concerns that may benefit from support. 

(Summary submitted by Randi Schuster, PhD, Center for Addiction Medicine, Department of Psychiatry)  

Discovery of Neurons in the Human Brain Able to Predict What We're Going to Say Before We Say It
Single-neuronal Elements of Speech Production in Humans
Khanna AR, Muñoz W, Kim YJ, Kfir Y, Paulk AC [et al.], Williams ZM
Published in Nature on 1/31/2024 | Press Release 

Our brains do a lot of work to produce speech -- we think about what word to say, then send instructions to our mouth and voice box to rapidly make the right sounds. Here, we recorded individual neurons from people while they spoke. We found that these neurons provided a detailed ‘map’ of the basic speech sounds of words before they were spoken and worked together in a tightly coordinated manner during language production. Together, these findings reveal neurons in the human brain that allow us to speak and that could improve our understanding of language disorders. 

(Summary submitted by Ziv Williams, MD, Department of Neurosurgery) 

First Comparative Analysis of Gut Microbiome of People with HIV Living in the U.S. And Sub-saharan Africa
HIV-associated Gut Microbial Alterations Are Dependent on Host and Geographic Context
Rocafort M, Gootenberg DB, Luévano JM Jr, Paer JM, Hayward MR [et al.], Kwon DS
Published in Nature Communications on 2/5/2024 

HIV-associated changes in the gut microbiome are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. We conducted the first comparative analysis of the gut microbiome of people with HIV (PWH) living in the U.S. and sub-Saharan Africa. We identified unique HIV-associated changes in the gut microbiome of those in the U.S., Uganda, and Botswana. Moreover, while HIV infection was consistently correlated with heightened systemic immune activation, the specific bacteria associated with this activation varied among PWH in the three regions. Our findings highlight the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease. 

(Summary submitted by Douglas S. Kwon, MD, PhD, Ragon Institute of MGH, MIT, and Harvard, Infectious Disease Unit, Department of Medicine) 

Resilience Training as Tool for Addressing and Reducing Loneliness among At-risk Young Adults
A Brief Resilience-Enhancing Intervention and Loneliness in At-Risk Young Adults: A Secondary Analysis of a Randomized Clinical Trial
DeTore NR, Burke A, Nyer M, Holt DJ
Published in JAMA Network Open on 2/5/2024 

There has been a worldwide epidemic of loneliness for the past several decades according to public health experts, and young people have been particularly affected. A randomized controlled study conducted by researchers in the MGH Resilience and Prevention Program and Psychiatry Department showed that a four-week-long behavioral intervention called Resilience Training (RT) significantly decreased loneliness in young adults. RT is a group-based intervention that focuses on teaching skills that improve the ability to handle stress and challenging social interactions. This research shows that RT is one scalable approach that could help combat the high rates of loneliness currently experienced by young people. 

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

When Police Kill Unarmed Black People, Other Black People in the General Us Population Experience Worse Sleep
Officer-Involved Killings of Unarmed Black People and Racial Disparities in Sleep Health
Venkataramani AS, Bair EF, Bor J, Jackson CL, Kawachi I [et al.], Tsai AC
Published in JAMA Internal Medicine on 2/5/2024 

Black people are more likely than white people to report inadequate sleep and poorer sleep quality. Structural racism is often hypothesized as a cause of these disparities. We conducted a quasi-experimental, difference-in-differences analysis of 2013-19 US national data from the Behavioral Risk Factor Surveillance Survey, American Time Use Survey, and Mapping Police Violence. Our findings show that when police kill unarmed Black people, other Black people in the general US population experience worse sleep, with substantive increases in short sleep and very short sleep. Comparable increases in short sleep and very short sleep were not observed among white people. 

(Summary submitted by Alexander C Tsai, MD, PhD, Department of Psychiatry) 

Targeted Approach for Gout Flare Prevention
Serum Urate and Recurrent Gout
McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK
Published in JAMA on 2/6/2024 

Gout affects >12 million US adults, with patients suffering very painful episodes of joint flares which may also increase risk of heart attack and stroke. Flares are caused by high levels of a molecule in the blood called urate. There is conflict between rheumatology (specialist) and primary care guidelines about how to manage gout, with rheumatologists aiming to get urate levels below a certain threshold. In this long-term study, nearly all gout flares occurred in patients with urate levels above the threshold (95-98% of cases occurred above such urate level targets). These findings support a targeted approach for flare prevention. 

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

Moderate Dose of Multivitamin Supplements after a Diagnosis of Nonmetastatic Colorectal Cancer Associated with Lower Mortality
Post-diagnostic Multivitamin Supplement Use and Colorectal Cancer Survival: A Prospective Cohort Study
He MM, Wang K, Lo CH, Zhang Y, Polychronidis G [et al.], Song M
Published in Cancer on 2/6/2024 

We prospectively assessed the post-diagnostic use of multivitamin supplements in relation to mortality among 2424 patients with stage I–III colorectal cancer. Compared to non-uses, users of multivitamin supplements at a dose of 3-5 tablets/week had 45% lower colorectal cancer-specific mortality. Compared to non-users in both pre- and post-diagnosis periods, new post-diagnostic users at dose of <10 tablets/week had a 19% lower all-cause mortality, whereas new users at a dose of ≥10 tablets/week and discontinued users had a 35-58% higher risk of mortality. In conclusion, use of multivitamin supplements at a moderate dose after a diagnosis of nonmetastatic colorectal cancer is associated with lower mortality, whereas a high dose (≥10 tablets/week) use is associated with higher mortality. 

(Summary submitted by Mingyang Song, MD, ScD, Clinical and Translational Epidemiology Unit, Department of Medicine)

Stigmatizing Language on Liver Transplant Center Websites May Discourage Patients from Seeking Treatment
Stigmatizing Language for Alcohol Use Disorder and Liver Disease on Liver Transplant Center Websites
Mahle R, Okanlawon A, Luther J, Louissaint J, Zhang W
Published in JAMA Network Open on 2/8/2024 | Press Release 

Our study examined how liver transplant centers and addiction psychiatry websites in the U.S. talk about alcohol-related health issues. We found that many use words that can be seen as judgmental or negative (like 'alcoholic') instead of more neutral, respectful terms (like 'alcohol use disorder'). This matters because the words used in healthcare can affect how patients feel and whether they seek help. Our findings suggest there's a need for these websites to use kinder language, which could help patients feel more comfortable and supported when they look for health information or treatment. 

(Summary submitted by Wei Zhang, MD, PHD, Division of Gastroenterology, Department of Medicine) 

Coaxing Macrophages to Fight Cancer
Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype
Enbergs N, Halabi EA, Goubet AG, Schleyer K, Fredrich IR [et al.], Weissleder R
Published in Advanced Science on 2/11/2024 

Our previous work found that high levels of tumor macrophages expressing the chemokine CXCL9 are associated with good clinical outcomes in cancer patients. Unfortunately, most tumor-associated macrophages do not express CXCL9. In this study, we develop a macrophage image screening approach to identify drugs that potentiate CXCL9 production. Here we show a triplet drug combination incorporated into a macrophage-avid nanoparticle that strongly enhances macrophage CXCL9 production and triggers remarkable anti-tumor efficacy in mouse cancer models. We envision leveraging deep molecular analysis of anti-tumor macrophages with novel drug screening methods to develop new cancer treatment methods. 

(Summary submitted by Ralph Weissleder, MD, PhD, and Christopher Garris, PhD, Center for Systems Biology) 

Hippocampus Is Essential for Offline Motor Learning
Maintenance of Procedural Motor Memory Across Brief Rest Periods Requires the Hippocampus
Mylonas D, Schapiro AC, Verfaellie M, Baxter B, Vangel M, Stickgold R, Manoach DS
Published in Journal of Neuroscience on 2/13/2024 

The hippocampus plays a critical role in memory, but is not generally associated with learning motor skills. Our study confirms that patients with amnesia due to hippocampal damage can learn a typing task, but we found that they learn it differently. Unlike their healthy peers, they lose speed across brief rest breaks and make up for their losses while typing. Together with our earlier discovery that amnesic patients fail to show the typical performance enhancement after a night of sleep, our study shows that the hippocampus is essential for offline motor learning, during both wakeful rest and sleep. 

(Summary submitted by Dara S. Manoach, PhD, Department of Psychiatry) 

Development of Alternative Therapeutic to High Dose IVIG
An Engineered Immunomodulatory IgG1 Fc Suppresses Autoimmune Inflammation through Pathways Shared with I.V. Immunoglobulin
Sneed SL, Reese BB, Laureano AF, Ratnapriya S, Fraschilla I [et al.], Anthony RM
Published in Journal of Clinical Investigation on 2/15/2024 

The introduction of a single amino acid mutation at 241-position into an IgG1 molecule results in potent anti-inflammatory activity. Here, we explore the pathways that are required for the mutated IgG1 to suppress autoimmune disease. We found there were shared pathways between the mutated IgG1 as the well-established immunomodulatory therapeutic, high dose intravenous immunoglobulin IVIG, which is routinely used to treat inflammatory and autoimmune diseases. Although effective, IVIG is expensive, takes hours to administer, and is subject to shortages. These studies enable the development of a recombinant IgG1 with mutated 241 position as an alternative therapeutic to high dose IVIG. 

(Summary submitted by Robert M. Anthony, PhD, Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine) 

Clonal Hematopoiesis and Atrial Fibrillation
Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation
Lin AE, Bapat AC, Xiao L, Niroula A, Ye J [et al.], Ebert BL
Published in Circulation on 2/15/2024 

Clonal hematopoeisis of indeterminate potential (CHIP) is an age-associated phenomenon resulting from somatic mutations in hematopoietic stem cells. CHIP is associated with atherosclerotic heart disease and heart failure; this study investigated its association with atrial fibrillation (AF). AF is a common heart rhythm disorder that increases in prevalence with advancing age. Human genetic data from the UK Biobank was analyzed to identify an associated between certain CHIP mutations and AF. This finding then was further corroborated using mouse models, recognizing a critical role for the NLRP3 inflammasome. This study adds to the growing evidence linking inflammation and AF. 

(Summary submitted by Aneesh C. Bapat, MD, Cardiovascular Research Center, Division of Cardiology, Department of Medicine) 

Greater Social Activity Can Provide Resilience Against Alzheimer’s Disease Pathology and Cognitive Decline
Social Activity Mediates Locus Coeruleus Tangle-related Cognition in Older Adults
Zide BS, Donovan NJ, Lee S, Nag S, Bennett DA, Jacobs HIL
Published in Molecular Psychiatry on 2/15/2024 

A small region deep in the brain, the locus coeruleus, plays an important role in cognition and behavior. While the locus coeruleus is also one of the first regions accumulating Alzheimer’s disease-related tau proteins, its integrity can be strengthened by lifetime cognitive and social activity. By investigating the locus coeruleus in 142 individuals at death, we found that greater tau burden in the locus coeruleus was associated with lower social activity during life and together, contributed to lower cognitive performance. These findings highlight the critical role the locus coeruleus plays very early in the disease, and that greater social activity can provide resilience against Alzheimer’s disease pathology and cognitive decline. 

(Summary submitted by Heidi I. Jacobs, PhD, Gordon Center for Medical Imaging, Department of Radiology) 

Gene Discovered Significantly Associated with Decreased Lung Cancer Risk among Smokers
CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility
Du M, Xin J, Zheng R, Yuan Q, Wang Z [et al.], Christiani DC
Published in Cancer Research on 2/15/2024 

Not all cigarette users develop lung cancer, highlighting the importance of the interaction between individual susceptibility and environmental exposure in the risk of developing lung cancer. The study aim was to describe the interaction between individual metabolizing ability of tobacco carcinogens and smoking intensity in altering or mediating this genetic susceptibility to smoking-related cancer. We analyzed associations of 43 tobacco carcinogen-metabolizing genes with lung cancer to examine their roles among large populations from the large International Lung Cancer Consortium and the UK Biobank. A variant in a gene known as CYP2A6, which codes for an enzyme that metabolizes nicotine, was significantly associated with decreased lung cancer risk among smokers. 

(Summary submitted by David C. Christiani, MD, MPH, Division of Pulmonary and Critical Care Medicine, Department of Medicine) 

Promising Results Suggest That the Human Immune System Can Be Programmed to Engage and Target Residual HIV-infected Cells
Selection of Epigenetically Privileged HIV-1 Proviruses during Treatment with Panobinostat and Interferon-α2a
Armani-Tourret M, Gao C, Hartana CA, Sun W, Carrere L [et al.], Lichterfeld M
Published in Cell on 2/16/2024 

HIV infection is one of the very few infectious diseases that cannot be cured; the 39 million people worldwide who live with HIV therefore need to take life-long antiviral suppression therapy. This paper describes a human clinical trial in which an immunological approach for reducing HIV persistence was tested. Two drugs were used in combination, one that makes infected cells more visible to immune cells, and one that increases the power of the immune system to kill infected cells. When administered together, these drugs were able to eliminate at least some of the infected cells. These promising results suggest that the human immune system can be programmed to engage and target residual HIV-infected cells, which may ultimately lead to a cure of HIV infection. 

(Summary submitted by Marie Armani Tourret, PhD, Ragon Institute of MGH, MIT and Harvard) 

Genomic Study to Improve Prediction of Type 2 Diabetes
Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology
Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X [et al.], Zeggini E
Published in Nature on 2/19/2024

International collaborations and data sharing mechanisms are essential to identify genetic risk variants that modify the risk of type 2 diabetes. Scientists at Massachusetts General Hospital, and The Broad Institute are part of the newly formed Type 2 Diabetes Global Genomics Initiative (T2D-GGI). The study encompasses 2.5 million individuals in which millions of genetic variants have been tested for association with type 2 diabetes. They have identified over 600 regions in the genome that are associated with modified risk for the disease. These findings can be used to improve prediction of type 2 diabetes and to identify new drug targets to treat the disease. 

(Summary submitted by Josep Mercader, PhD, Broad Institute) 

Private Equity Investment Within Surgical Specialties Created Increased Practice Consolidation
Private Equity Investment in Surgical Care
Sievers MT, Neevel A, Diaz A, Rouanet E, Sheetz K [et al.], Chhabra KR
Published in Annals of Surgery on 2/19/2024 

Private equity groups have recently invested in surgical care at an unprecedented rate. Between 2015-2019, we identified 58 private equity transactions accounting for 199 practice sites and 1,405 physicians—primarily affecting digestive disease, orthopedics, urology, vascular surgery, and plastic/cosmetic surgery. 

(Summary submitted by Karan R Chhabra, MD, MSC, Department of Surgery)  

Patients Achieving Surgical Remission of Cushing’s Disease Have Higher Incidence of Autoimmune Disease
Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study
Nyanyo DD, Mikamoto M, Galbiati F, Remba-Shapiro I, Bode K [et al.], Nachtigall LB
Published in Annals of Internal Medicine on 2/20/2024 

Cushing’s Disease (CD) causes cortisol excess due to an ACTH secreting pituitary adenoma. Autoimmune disease after remission of CD has been observed, but scarcely reported. This study reveals that patients with CD after surgical remission were over 7 times more likely than controls to develop new-onset autoimmune disease within 3 years. The cumulative incidence was 10.4%; associated with family history of autoimmune disease and lower doses of postoperative glucocorticoids. It is important to recognize new inflammatory conditions, as distinct from steroid withdrawal, after remission of CD. These findings have implications for understanding autoimmune disease triggers and relationship to cortisol fluctuations. 

(Summary submitted by Lisa Nachtigall, MD, Neuroendocrine Unit, Endocrine Division, Department of Medicine) 

Substudy of REPRIEVE Trial Reveals How Statin Therapy Prevents Cardiovascular Disease in People with HIV
Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial
Lu MT, Ribaudo H, Foldyna B, Zanni MV [et al.], Grinspoon SK; REPRIEVE Trial Writing Group
Published in JAMA Cardiology on 2/21/2024 | Press Release 

People with HIV are at high risk of cardiovascular events including heart attack and stroke. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) randomized 7,769 people with HIV to pitavastatin, a daily cholesterol lowering pill, versus placebo, finding that the statin reduces the risk of cardiovascular events by 35%. The REPRIEVE mechanistic substudy performed baseline and 2-year coronary CT imaging and blood testing in 804 REPRIEVE participants. The main finding was that pitavastatin reduced coronary plaque buildup and inflammation. This helps explain the 35% reduction in heart attack or stroke seen in REPRIEVE. 

(Summary submitted by Michael T. Lu, MD, MPH, Cardiovascular Imaging Division, Department of Radiology) 

Mouse Model Recapitulates Patient Symptoms and Provides Robust Cellular and Molecular Benchmarks for Therapeutic Testing
Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction
Deehan MA, Kothuis JM, Sapp E, Chase K, Ke Y [et al.], DiFiglia M
Published in Journal of Neuroscience on 2/22/2024 

A missense mutation (c892C>T) in the gene nucleus accumbens associated 1 (NACC1) causes a profound delay in development accompanied by intellectual disability, epilepsy, microcephaly, irritability, and other problems. NACC1 normally functions in repressing transcription of other genes but how the mutation interferes with its normal function in the nervous system is unknown. We engineered the first known mouse model of NACC1 harboring the missense mutation. Mutant mice showed reduced weight gain, anxiety-like behavior, epileptiform discharges, and motor changes that mimic aspects of patient symptoms. Mice also exhibited an altered expression of the mutant protein, as well as genes and proteins involved with synaptic functions. Overall, these findings provide a strong foundation to better understand disease mechanisms and evaluate therapeutic interventions. 

(Summary submitted by Mark Deehan, PhD, and Marian DiFiglia PhD, Department of Neurology) 

CAR-TEAM Cells Enable Modification of Tumor Stroma, Leading to Increased Elimination of PDAC Tumors
Mesothelin CAR T-cells Secreting anti-FAP/anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and Its Stroma
Wehrli M, Guinn S, Birocchi F, Kuo A, Sun Y [et al.], Maus MV
Published in Clinical Cancer Research on 2/23/2024 

CAR T cells are a promising cancer treatment that reprograms a patient’s immune to target their cancer cells. This has worked well for blood cancers but has not worked well for solid tumors due to the presence of other cells that suppress CAR T cell function. In this study, we designed CAR T cells that target not only the cancer cells but also the suppressive cells within solid tumors by traveling to the tumor and releasing a second drug. We demonstrate that these CAR T cells are more effective at eliminating tumors in models of pancreatic cancer compared to CAR T cells that do not deliver a second drug or target suppressive cells. 

(Summary submitted by Trisha Berger, PhD, Cellular Immunotherapy Program, Mass General Cancer Center) 

Study Discovers Neurons in the Human Brain that can Predict What We're Going to Say Before We Say It
Featuring Ziv Williams, MD 

Researchers identified ‘speech neurons’ in the human brain that act in a coordinated way as a person plans and produces words during language production. Tracking these neurons allowed the scientists to predict what combination of word sounds a person will produce before even saying them. The findings could lead to the treatment of language disorders through the development of new brain-machine interfaces capable of producing synthetic speech. 

Stigmatizing Language on Liver Transplant Center Websites May Discourage Patients from Seeking Treatment
Featuring Rachael Mahle, MD and Wei Zhang, MD, PhD 

Researchers found that the use of stigmatizing words like “alcoholic,” “alcoholism” and “alcohol abuse” are used extensively on the websites of liver transplant centers in the U.S., potentially affecting the care of patients and their willingness to seek treatment. The study calls on transplant centers and their hospital systems to improve and update their website language to conform with patient-first, more respectful terminology which can lead to better health outcomes. 

Brief Psychological Interventions Can Reduce Post-Traumatic Stress Symptoms After Childbirth
Featuring Sharon Dekel Tsvetkov, PhD, MPhil 

Women can develop PTSD after a traumatic or medically complicated birth, which poses risks for themselves and their children. Researchers from Massachusetts General Hospital evaluated the results of 41 clinical trials that assessed interventions to prevent postpartum PSTD. They found that trauma-focused therapies and midwife-led dialogue were effective, especially when administered in the early days after childbirth. 

Substudy of REPRIEVE Trial Reveals How Statin Therapy Prevents Cardiovascular Disease in People with HIV
Featuring Michael T. Lu, MD, MPH 

In a substudy of the phase 3 REPRIEVE randomized controlled trial trial, pitavastatin reduced plaque buildup in the heart’s coronary arteries and lowered blood markers of inflammation. The findings may explain how pitavastatin reduced the risk of adverse cardiovascular events by 35% over 5 years in the REPRIEVE analysis. 

Learning More About the Structure of Viruses Used for Insecticides and Therapeutic Gene Delivery
Featuring Friederike Benning, PhD and Luke Chao, PhD 

Friederike Benning, PhD, a research fellow in the Department of Molecular Biology at Massachusetts General Hospital, is the first author of a new study in Nature Communications, "Helical Reconstruction of VP30 Reveals Principles for Baculovirus Nucleocapsid Assembly". Luke Chao, PhD, is senior author of the study. 

Exploring a New Approach to Manage and Diagnose a Devastating Subset of Alzheimer’s Disease
Featuring Ana Rita Agra de Almeida Quadros, Clotilde Lagier-Tourenne, PhD, and Sudeshna Das, PhD 

Ana Rita Agra de Almeida Quadros, PhD, a research fellow in the Department of Neurology at Massachusetts General Hospital, is co-lead author of a new study in Acta Neuropathologica, "Cryptic Splicing of Stathmin-2 and unc13a Mrnas Is a Pathological Hallmark of Tdp-43-Associated Alzheimer’s Disease". Clotilde Lagier-Tourenne, PhD, and Sudeshna Das, PhD, of the Department of Neurology at Mass General are co-corresponding authors along with Nilüfer Ertekin-Taner, MD, PhD, of the Mayo Clinic. 

A Two-Part Priming Strategy to Increase the Sensitivity of Liquid Biopsies
Featuring Shervin Tabrizi, MD 

Shervin Tabrizi, MD, a physician-investigator at the Mass General Cancer Center and an instructor in Radiation Oncology at Harvard Medical School, is co-lead author of a new study in Science, "Priming Agents Transiently Reduce the Clearance of Cell-Free DNA to Improve Liquid Biopsies". 

Benzodiazepines Associated with Worse Disease Progression in Progressive Supranuclear Palsy
Featuring Anne-Marie Wills, MD, MPH 

Anne-Marie Wills, MD, MPH, director of the CurePSP Center of Care at Massachusetts General Hospital and associate professor of Neurology at Harvard Medical School, is the senior author of a new letter in JAMA Neurology, "Concomitant Medications for Progressive Supranuclear Palsy". 

Evaluating the Implementation of a Pediatric Healthy Lifestyle Program in Primary Care Settings
Featuring Meg Simione, PhD 

Meg Simione, PhD, an investigator at Mass General for Children and an assistant professor of Pediatrics at Harvard Medical School, and colleagues recently published a paper in JAMA Network Open, titled "Evaluating the Implementation of the Connect for Health Pediatric Weight Management Program". 

Recreational Cannabis Legalization and Pediatric Exposures in Massachusetts, United States
Featuring Dias Argandykov, MD, Michael Flaherty, DO and Toby Raybould 

Dias Argandykov, MD, a surgical resident at Massachusetts General Hospital, is lead author of a new study in the journal Injury Prevention, "Recreational Cannabis Legalization and Pediatric Exposures in Massachusetts, United States". Michael Flaherty, DO, a pediatric critical care physician at Mass General for Children, is senior author, and Toby Raybould, Trauma Prevention Manager at Mass General, is among the authors. 

Benchmarks: Mass General Research News and Notes for Feb. 2, 2024 

Researchers identify neurons that help predict what you’ll say before you speak, advancing liquid biopsies, the tweets of the week and more. 

Snapshot of Science: Mass General’s High Impact Research Publications for January 2024 

PTSD from childbirth, Brain Care Score and much more 

Through the Magnifying Glass: The Cardiometabolic Health and Hormones Clinic
Featuring Emily Lau, MD, MPH 

A close-up look at the Cardiometabolic Health and Hormones Clinic and how they are working to understand how hormones impact heart disease. 

Mass General Researchers Share Science-Backed Ways to Improve Your Heart Health 

Researchers and clinicians from Massachusetts General Hospital share actionable steps you can take to have a healthy heart! 

Benchmarks: Mass General Research News and Notes for Feb. 9, 2024 

Stigmatizing language could be a barrier to liver transplant patients, Harvard Gazette highlights the MGRI image awards and lots more. 

Claflin Awards Help Moms Thrive in Science and Medicine at Mass General 

This year’s Claflin award winners share what the recognition means to them and their careers. 

How a Chance Encounter Led One Mass General Researcher on a Decade-Long Journey of Discovery
Featuring Alexander Marneros, MD, PhD 

What started as an investigation into a rare skin disease led one researcher to new insights about kidney formation and function. 

Through the Magnifying Glass: The Boland Lab 

Genevieve Boland, MD, PhD, a physician-investigator in the Cancer Center at Mass General, is researching skin cancer and related diseases. 

Rare Diseases Day: Q&A with a Mass General Investigator
Featuring Vanessa Merker, PhD 

Vanessa Merker, PhD, has spent her 14-year career at Mass General working to improve care for patients with schwannomatosis and NF2.