Genetic Diversity in Immune System Can Affect Likelihood to Develop Lung Cancer
An Immunogenetic Basis for Lung Cancer Risk
Krishna C, Tervi A, Saffern M, Wilson EA, Yoo SK [et al.], Chowell D
Published in Science on 2/23/2024 | *Summary available

Link between Tobacco Product Use and Increased Risk of Suicidal Behaviors in Children
Use of Tobacco Products and Suicide Attempts Among Elementary School-Aged Children
Lee PH, Tervo-Clemmens B, Liu RT, Gersten MB, Jung JY, Janes AC, Gilman J
Published in JAMA Network Open on 2/26/2024 | *Summary available

Survey Finds Most Pediatricians Unprepared to Treat Teens with Opioid Use Disorder
Treating Adolescent Opioid Use Disorder in Primary Care
Hadland SE, Burr WH, Zoucha K, Somberg CA, Camenga DR
Published in JAMA Pediatrics on 2/26/2024 | *Summary available | Press Release

A Potential Therapeutic Target for PTH1R Malfunction
Backbone Modification Provides a Long-Acting Inverse Agonist of Pathogenic, Constitutively Active PTH1R Variants
Liu S, Daley EJ, Tran LM, Yu Z, Reyes M [et al.], Gardella TJ
Published in Journal of American Chemical Society on 2/28/2024

Remarkable Capacity of Skeletal Muscles to Govern Bionic Prostheses
Peripheral Neural Interfaces: Skeletal Muscles Are Hyper-reinnervated According to the Axonal Capacity of the Surgically Rewired Nerves
Tereshenko V, Dotzauer DC, Schmoll M, Harnoncourt L, Carrero Rojas G [et al.], Aszmann OC
Published in Science Advances on 2/28/2024 | *Summary available

Broad and Long-lasting Disaster Impacts on Health and Mortality
Impact of Extreme Weather Events on Healthcare Utilization and Mortality in the United States
Salas RN, Burke LG, Phelan J, Wellenius GA, Orav EJ, Jha AK
Published in Nature Medicine on 2/29/2024 | *Summary available

Hypothesis of a Sterile Pancreas Environment
Absence of a Pancreatic Microbiome in Intraductal Papillary Mucinous Neoplasm
Pust MM, Rocha Castellanos DM, Rzasa K, Dame A, Pishchany G [et al.], Xavier RJ
Published in Gut on 3/1/2024 | *Summary available

Prolonging Skin Graft Transplant Survival with T cell Innovation
A Humanized IL-2 Mutein Expands Tregs and Prolongs Transplant Survival in Preclinical Models
Efe O, Gassen RB, Morena L, Ganchiku Y, Al Jurdi A [et al], Riella LV
Published in Journal of Clinical Investigation on 3/1/2024 | *Summary available

Nationwide Survey on Recovery Community Centers for Substance Use Disorder
A Nationwide Survey Study of Recovery Community Centers Supporting People in Recovery From Substance Use Disorder
Hoeppner BB, Simpson HV, Weerts C, Riggs MJ, Williamson AC [et al.], Kelly JF
Published in Journal of Addition Medicine on 3/1/2024 | *Summary available | Research Spotlight

Investigating the Success of a Combination Drug Therapy for Specific Breast Cancers
Trastuzumab and Pertuzumab in Patients with Non-Breast/Gastroesophageal HER2-Amplified Tumors: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol J
Connolly RM, Wang V, Hyman DM, Grivas P, Mitchell EP [et al.], Flaherty KT
Published in Clinical Cancer Research on 3/4/2024

Investigating a Potential Biomarker That Could Be Contributing to Uterine Cancer Growth
Targeting Galectin 3 Illuminates its Contributions to the Pathology of Uterine Serous Carcinoma
Matoba Y, Zarrella DT, Pooladanda V, Azimi Mohammadabadi M, Kim E [et al.], Rueda BR
Published in British Journal of Cancer on 3/4/2024 | *Summary available

KIN-3248 as a Potential Cancer Treatment
The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Balasooriya ER, Wu Q, Ellis H, Zhen Y, Norden BL [et al], Bardeesy N
Published in Clinical Cancer Research on 3/4/2024 | *Summary available

Genetic Clusters and Biological Pathways That May Explain Differences in Type 2 Diabetes Risk
Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes
Smith K, Deutsch AJ, McGrail C, Kim H, Hsu S [et al.], Udler MS
Published in Nature Medicine on 3/5/2024 | Press Release

New Insights into the Silencing of X Chromosome Genes Passed on From Fathers to Daughters
Imprinted X Chromosome Inactivation at the Gamete-to-embryo Transition
Wei C, Kesner B, Yin H, Lee JT
Published in Molecular Cell on 3/7/2024 | *Summary available | Press Release

Adding Brain Stimulation to Current Treatment-Resistant Depression Therapy May be Effective to Lessen Symptoms
Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders with Treatment Resistant Depression (ASCERTAIN-TRD) A Randomized Clinical Trial
Papakostas GI, Trivedi MH, Shelton RC, Iosifescu DV, Thase ME [et al.], Fava M
Published in Molecular Psychiatry on 3/7/2024 | *Summary available

Epigenetic Profiling Reveals Key Genes That Play a Role in Calcium Regulation
Epigenetic Profiling Reveals Key Genes and Cis-regulatory Networks Specific to Human Parathyroids
Jung YL, Zhao W, Li I, Jain D, Epstein CB [et al.], Mannstadt M
Published in Nature Communications on 3/7/2024 | *Summary available  

Highlighting an Increase in Mental Health Needs for Adolescents and Young Adults
Mental Health-Related Outpatient Visits Among Adolescents and Young Adults, 2006-2019
Ahn-Horst RY, Bourgeois FT
Published in JAMA Network Open on 3/7/2024

Long-term Review of a Diagnostic Marker for Pancreatic Cysts
Revisiting the Performance of Cyst Fluid Carcinoembryonic Antigen as a Diagnostic Marker for Pancreatic Mucinous Cysts: A Comprehensive 20-year Institutional Review
Kwan MC, Pitman MB, Fernandez-Del Castillo C, Zhang ML
Published in Gut on 3/7/2024 | *Summary available

Investigating a Combination Drug Therapy for Advanced Solid Tumors
Phase 1/2 Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors
Corcoran RB, Do KT, Kim JE, Cleary JM, Parikh AR [et al.], Shapiro GI
Published in Clinical Cancer Research on 3/8/2024

Cost-Effectiveness of Early Intervention: Treating Perinatally Acquired Hepatitis C Virus in 3-Year-Olds
Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus
Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL
Published in JAMA Pediatrics on 3/11/2024 | *Summary available | Research Spotlight

Investigating Disparities in the Documentation of Patient Race and Ethnicity
Frequency of Discordant Documentation of Patient Race and Ethnicity
Salhi RA, Macy ML, Samuels-Kalow ME, Hogikyan M, Kocher KE
Published in JAMA Network Open on 3/11/2024 | *Summary available | Research Spotlight

A Simpler and More Eco-Friendly Route to a New Series of Dibenzo[b,d]azepines
Synthesis of Easily-modified and Useful Dibenzo-[b,d]Azepines by Palladium(II)-catalyzed Cyclization/Addition with a Green Solvent
Cheng H, Liu R, Fang S, Li Z, Zhang D [et al.], Shao L
Published in Chemical Communications on 3/12/2024

Enhancing Health Insurance Literacy in Childhood Cancer Survivors
Health Insurance Navigation Tools Intervention: A Pilot Trial Within the Childhood Cancer Survivor Study
Park ER, Kirchhoff AC, Donelan K, Perez GK, McDonald A [et al.], Kuhlthau KA
Published in JCO Oncology Practice on 3/12/2024 | *Summary available | Research Spotlight

Rare Genetic Variant Exposes a Signaling Switch Required for Antifungal Immunity
Translational Genetics Identifies a Phosphorylation Switch in CARD9 Required for Innate Inflammatory Responses
Brandt M, Cao Z, Krishna C, Reedy JL, Gu X [et al.], Xavier RJ
Published in Cell Reports on 3/13/2024 | *Summary available

Preliminary Clinical Trial Results Show ‘Dramatic and Rapid’ Regression of Glioblastoma after Next Generation CAR-T Therapy
Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma
Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW [et al.], Maus MV
Published in New England Journal of Medicine on 3/13/2024 | *Summary available | Press Release

Using Machine Learning to Prevent Post-operative Complications
A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery
Beqari J, Powell J, Hurd J, Potter AL, McCarthy M [et al.], Li X
Published in Annals of Surgery on 3/14/2024 | *Summary available

Investigating Adherence to Neonatal Phototherapy Guidelines
Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline
Sarathy L, Chou JH, Romano-Clarke G, Darci KA, Lerou PH
Published in Pediatrics on 3/14/2024 | *Summary available

New Non-Invasive Test for Colorectal Cancer Screening
A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening
Chung DC, Gray DM 2nd, Singh H, Issaka RB, Raymond VM [et al.], Grady WM
Published in New England Journal of Medicine on 3/14/2024 | *Summary available

Studying the Genetic Risk for Psychosis and How Neurotransmitters Contribute
Association of Neurotransmitter Pathway Polygenic Risk with Specific Symptom Profiles in Psychosis
Warren TL, Tubbs JD, Lesh TA, Corona MB, Pakzad SS [et al.], Nord AS
Published in Molecular Psychiatry on 3/15/2024 | *Summary available

Macrophages Role in Tissue Repair
Mechanosensing Regulates Tissue Repair Program in Macrophages
Meizlish ML, Kimura Y, Pope SD, Matta R, Kim C [et al.], Medzhitov R
Published in Science Advances on 3/15/2024 | *Summary available

Aspirin Reduces Liver Fat in Clinical Trial of the Most Common Cause of Chronic Liver Disease
Aspirin for Metabolic Dysfunction-Associated Steatotic Liver Disease Without Cirrhosis: A Randomized Clinical Trial
Simon TG, Wilechansky RM, Stoyanova S, Grossman A, Dichtel LE [et al.], Chan AT
Published in JAMA on 3/19/2024 | Press Release

Stem-immunity Hubs Associated with Response to Immunotherapy
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
Chen JH, Nieman LT, Spurrell M, Jorgji V, Elmelech L [et al.], Hacohen N
Published in Nature Immunology on 3/19/2024 | *Summary available | Research Spotlight

Genetic Diversity in Immune System Can Affect Likelihood to Develop Lung Cancer
An Immunogenetic Basis for Lung Cancer Risk
Krishna C, Tervi A, Saffern M, Wilson EA, Yoo SK [et al.], Chowell D
Published in Science on 2/23/2024

Cancer risk depends on a mix of factors, including genes you inherit, mistakes that can happen when your cells copy their DNA, and things in your environment like smoking. But we're not completely sure how our immune system's genetic makeup affects cancer risk. We studied two large databases and found that having genetic diversity in a set of genes called HLA can lower the risk of getting lung cancer, especially in people who smoke. The results show that inherited factors affect cancer risk and that genetic diversity in our immune system can affect how likely someone is to get lung cancer, especially if they smoke.

(Summary submitted by Hanna M Ollila, PhD, Center for Genomic Medicine)

Link between Tobacco Product Use and Increased Risk of Suicidal Behaviors in Children
Use of Tobacco Products and Suicide Attempts Among Elementary School-Aged Children
Lee PH, Tervo-Clemmens B, Liu RT, Gersten MB, Jung JY, Janes AC, Gilman J
Published in JAMA Network Open on 2/26/2024

In a study involving over 9,000 U.S. children aged 9 to 10, researchers have identified a link between tobacco product use, including e-cigarettes and vaping, and increased risk of suicidal behaviors. The findings reveal that young tobacco users are 3 to 5 times more likely to attempt suicide compared to their non-using peers, a risk factor that remained significant even after adjusting for a variety of other potential influences. Notably, the use of alcohol, cannabis, and prescription drugs did not show a significant connection to suicide attempts. These findings highlight the urgent need for further research and preventive strategies specifically targeting tobacco product use among young children to mitigate these risks.

(Summary submitted by Phil H Lee, PhD, Center for Genomic Medicine)

Survey Finds Most Pediatricians Unprepared to Treat Teens with Opioid Use Disorder
Treating Adolescent Opioid Use Disorder in Primary Care
Hadland SE, Burr WH, Zoucha K, Somberg CA, Camenga DR
Published in JAMA Pediatrics on 2/26/2024 | Press Release

We surveyed pediatricians from across the US and found that even though as many as 1 in 4 had encountered a teen with opioid addiction, most felt unprepared to counsel teens on opioids. Most pediatricians typically referred teens with opioid addiction to other places, such as addiction treatment programs, rather than providing treatment in primary care, just as they would other medical and mental health conditions.

(Summary submitted by Scott E Hadland, MD, MPH, Division of Adolescent and Young Adult Medicine, Mass General for Children)

Remarkable Capacity of Skeletal Muscles to Govern Bionic Prostheses
Peripheral Neural Interfaces: Skeletal Muscles Are Hyper-reinnervated According to the Axonal Capacity of the Surgically Rewired Nerves
Tereshenko V, Dotzauer DC, Schmoll M, Harnoncourt L, Carrero Rojas G [et al.], Aszmann OC
Published in Science Advances on 2/28/2024

Bionic reconstruction has significantly advanced, emerging as a viable therapeutic modality for restoring extremity function in cases where biological hand replantation or transplantation is not feasible. However, the high-resolution transfer of information from the brain to the machine remains a challenging issue. The study has revealed that skeletal muscles can serve as a high-resolution interface by integrating a substantial volume of neural information from the spinal cord after the surgical rewiring of peripheral nerves. These findings underscore the remarkable capacity of skeletal muscles to act as biological amplifiers of neural information from the spinal cord, governing bionic prostheses.

(Summary submitted by Vlad Tereshenko, PhD, Department of Surgery)

Broad and Long-lasting Disaster Impacts on Health and Mortality
Impact of Extreme Weather Events on Healthcare Utilization and Mortality in the United States
Salas RN, Burke LG, Phelan J, Wellenius GA, Orav EJ, Jha AK
Published in Nature Medicine on 2/29/2024

This study evaluated the impacts of major floods, severe storms, hurricanes, and winter storms on emergency departments (ED) visits, hospitalizations, and deaths among Medicare beneficiaries in the United States. ED visits were increased through the second week. Notably, deaths remained elevated for six weeks, the end of the study period. The counties that experienced the greatest damage had death rates two to four times higher – and more than twice the ED usage – compared to all impacted counties. This exposes broad and long-lasting disaster impacts, and the urgency of tracking these outcomes to better inform how we adapt to climate change.

(Summary submitted by Renee N. Salas, MD, MS, MPH, Department of Emergency Medicine)

Hypothesis of a Sterile Pancreas Environment
Absence of a Pancreatic Microbiome in Intraductal Papillary Mucinous Neoplasm
Pust MM, Rocha Castellanos DM, Rzasa K, Dame A, Pishchany G [et al.], Xavier RJ
Published in Gut on 3/1/2024

Recent studies have suggested the existence of a pancreatic cyst microbiome potentially contributing to inflammation in patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors of pancreatic cancer. Inflammation, in turn, has been linked to IPMN progression. Intrigued by these findings, we collected cyst fluid samples during surgery, avoiding passage through the gastrointestinal tract. By implementing further contamination controls, our data support the hypothesis of a sterile pancreas environment. Bacterial DNA signals in a few outlier samples were associated with recent invasive interventions, suggesting other inflammatory drivers of IPMN progression, and challenging the benefit of antibiotic intervention in this context.

(Summary submitted by Marie-Madlen Pust, PhD, Center for Computational and Integrative Biology)

Prolonging Skin Graft Transplant Survival with T cell Innovation
A Humanized IL-2 Mutein Expands Tregs and Prolongs Transplant Survival in Preclinical Models
Efe O, Gassen RB, Morena L, Ganchiku Y, Al Jurdi A [et al], Riella LV
Published in Journal of Clinical Investigation on 3/1/2024

The body's immune system protects us from harmful invaders like viruses and bacteria, but it can also see transplanted organs as threats, leading to rejection. To prevent this, patients take drugs to weaken the immune system, but these drugs have side effects and make the body vulnerable to infections and other diseases. Our team focuses on a special type of immune cell called regulatory T cells (Tregs) that can calm down the immune response. We developed a new drug called mutein IL-2 that boosts Tregs specifically, helping the body accept transplanted organs better without needing as many strong drugs. This could make organ transplants safer and more successful.

(Summary submitted by Leonardo V. Riella, MD, PhD, FASN, FAST, Legorreta Center for Clinical Transplant Tolerance, Department of Surgery)

Nationwide Survey on Recovery Community Centers for Substance Use Disorder
A Nationwide Survey Study of Recovery Community Centers Supporting People in Recovery From Substance Use Disorder
Hoeppner BB, Simpson HV, Weerts C, Riggs MJ, Williamson AC [et al.], Kelly JF
Published in Journal of Addition Medicine on 3/1/2024 | Research Spotlight

Our team conducted an online survey with directors of recovery community centers (RCCs; 198 identified nationwide; 62% participated in the survey). RCCs are community centers run by people with lived experience to support people seeking recovery from substance use disorder by providing services (e.g., recovery coaching) and opportunity to engage in recovery-supportive social activities. Results show that RCCs successfully engage racial/ethnic minority groups and young adults, who are often under-engaged in treatment settings. Interest in working more closely with prescribers is high among RCCs; the RCC environment is a welcoming environment for people taking medications to overcome problematic substance use.

(Summary submitted by Bettina B Hoeppner, PhD, Department of Psychiatry)

Investigating a Potential Biomarker That Could Be Contributing to Uterine Cancer Growth
Targeting Galectin 3 Illuminates its Contributions to the Pathology of Uterine Serous Carcinoma
Matoba Y, Zarrella DT, Pooladanda V, Azimi Mohammadabadi M, Kim E [et al.], Rueda BR
Published in British Journal of Cancer on 3/4/2024

Briefly, this manuscript highlights the contribution of Galectin 3, a glycan recognition protein, in promoting the highly aggressive features associated with uterine serous cancer (USC). Albeit rare, USC accounts for 40% of uterine cancer deaths due to its metastatic potential and the lack of effective therapeutic strategies. Identifying targetable proteins, like Galectin 3, that contribute to the pathology of this lethal disease can serve to inform the development of alternative treatment strategies.

(Summary submitted by Bo R. Rueda, PhD, Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology)

KIN-3248 as a Potential Cancer Treatment
The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Balasooriya ER, Wu Q, Ellis H, Zhen Y, Norden BL [et al], Bardeesy N
Published in Clinical Cancer Research on 3/4/2024

Our study introduces KIN-3248, a new drug aimed at fighting cancers that have abnormalities in the FGFR gene, such as subsets of bile duct and bladder cancer. Other drugs targeting FGFR can gradually lose effectiveness when new mutations in this gene arise within the cancer cells. KIN-3248 remains effective against some of these mutations that make treatment difficult. Our findings show that KIN-3248 both directly combats these tough cancer cells and also works better when combined with other treatments. This research could lead to more effective ways to treat these challenging cancers.

(Summary submitted by Nabeel Bardeesy, PhD, Mass General Cancer Center)

New Insights into the Silencing of X Chromosome Genes Passed on From Fathers to Daughters
Imprinted X Chromosome Inactivation at the Gamete-to-embryo Transition
Wei C, Kesner B, Yin H, Lee JT
Published in Molecular Cell on 3/7/2024 | Press Release

Investigators have found that while some genes on the X chromosome passed from father to daughter become newly inactivated during embryo development, others are inherited from the father in a surprisingly pre-silenced state. These pre-suppressed genes tended to be the oldest in terms of their evolutionary age on the X-chromosome. The findings suggest a conserved mechanism whereby the paternal germline ensures that sons and daughters get the same “dose” of the X chromosome during development.

(Summary submitted by Jeannie T. Lee, MD, PhD, Department of Molecular Biology)

Adding Brain Stimulation to Current Treatment-Resistant Depression Therapy May be Effective to Lessen Symptoms
Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders with Treatment Resistant Depression (ASCERTAIN-TRD) A Randomized Clinical Trial
Papakostas GI, Trivedi MH, Shelton RC, Iosifescu DV, Thase ME [et al.], Fava M
Published in Molecular Psychiatry on 3/7/2024

Patients with treatment-resistant depression have experienced insufficient symptom improvement following treatment with two or more antidepressant therapies. An unanswered question is whether adding a treatment for these patients to their medications is superior to switching them to a new antidepressant altogether. Our team sought to answer this question by comparing adding on either repetitive transcranial magnetic therapy (rTMS) or an atypical antipsychotic agent versus switching their medications to venlafaxine. These three options were chosen due to their popularity and widespread use. We found that adding rTMS but not adding aripiprazole was more effective than changing antidepressants in treating depression. These findings suggest that rTMS should be considered early on as an addition to patients' treatment regimens for this patient population.

(Summary submitted by George I. Papakostas, MD, and Maurizio Fava, MD, Clinical Trials Network and Institute, Department of Psychiatry)

Epigenetic Profiling Reveals Key Genes That Play a Role in Calcium Regulation 
Epigenetic Profiling Reveals Key Genes and Cis-regulatory Networks Specific to Human Parathyroids 
Jung YL, Zhao W, Li I, Jain D, Epstein CB [et al.], Mannstadt M 
Published in Nature Communications on 3/7/2024

Calcium is essential for life, and its levels in our blood need to be tightly controlled. This control comes from a hormone called parathyroid hormone (PTH), made by small glands in our neck. But how do these parathyroid glands manage such a precise task? Working with other scientists, we've created a detailed map of the parathyroid gland's "epigenetic landscape" for the first time. This map reveals how the gland works on a very detailed level and helps us understand why calcium levels vary among people. 

(Summary submitted by Michael Mannstadt, MD, Endocrine Unit, Department of Medicine) 

Long-term Review of a Diagnostic Marker for Pancreatic Cysts
Revisiting the Performance of Cyst Fluid Carcinoembryonic Antigen as a Diagnostic Marker for Pancreatic Mucinous Cysts: A Comprehensive 20-year Institutional Review
Kwan MC, Pitman MB, Fernandez-Del Castillo C, Zhang ML
Published in Gut on 3/7/2024

This study looked at the use of a marker called carcinoembryonic antigen (CEA), found in the fluid of pancreatic cysts, to distinguish between mucinous cysts that could turn cancerous and those that are less likely to. Previous studies have shown that higher levels of CEA are found in mucinous cysts. By examining data spanning over 20 years, this study found that raising the threshold for CEA could improve the test's specificity, helping doctors more accurately identify cysts with a higher risk of becoming cancerous. This adjustment could lead to more accurate management and surveillance, potentially preventing the development of pancreatic cancer.

(Summary submitted by M Lisa Zhang, MD, Department of Pathology)

Cost-Effectiveness of Early Intervention: Treating Perinatally Acquired Hepatitis C Virus in 3-Year-Olds
Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus
Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL
Published in JAMA Pediatrics on 3/11/2024 | Research Spotlight

Hepatitis C virus (HCV) can cause a chronic infection, damaging the liver. HCV infections are increasing among pregnant people in the context of the opioid epidemic, which raises concern about passing the virus to infants during pregnancy. Safe and effective treatment is available for children as young as 3 years old. But most children who are exposed to HCV are not screened, and few with HCV infection access treatment. This study used mathematical modeling to simulate 1000 children with perinatally-acquired HCV. It looked at what happens when children are treated at different ages: 3, 6, 12, and 18 years old. Authors found that treating earlier helped children with HCV live longer and decreased healthcare costs over their lifetime.

(Summary submitted by Megan Rose Curtis, MD, Infectious Disease Unit, Department of Medicine)

Investigating Disparities in the Documentation of Patient Race and Ethnicity
Frequency of Discordant Documentation of Patient Race and Ethnicity
Salhi RA, Macy ML, Samuels-Kalow ME, Hogikyan M, Kocher KE
Published in JAMA Network Open on 3/11/2024 | Research Spotlight

Race and ethnicity get collected at many clinical visits, including in the emergency department. This information is vital in detecting and addressing gaps in care and health outcomes. However, little is known about how these recording patterns may change over time and, as a result, how our use of these data is impacted. Using a large state dataset, we find that the error rate may be higher than previously realized – especially for children.

(Summary submitted by Rama A. Salhi, MD MHS MSc, Department of Emergency Medicine)

Enhancing Health Insurance Literacy in Childhood Cancer Survivors
Health Insurance Navigation Tools Intervention: A Pilot Trial Within the Childhood Cancer Survivor Study
Park ER, Kirchhoff AC, Donelan K, Perez GK, McDonald A [et al.], Kuhlthau KA
Published in JCO Oncology Practice on 3/12/2024 | Research Spotlight

This study presents findings of a pilot RCT investigating the feasibility, acceptability, and preliminary efficacy of the Health Insurance Navigation Tools (HINT) intervention designed to aid childhood cancer survivors understand and access their health insurance. The study demonstrated HINT’s feasibility and acceptability and elucidated the benefits of HINT, compared to enhanced usual care, on improving health insurance literacy, which will believe will reduce the impact of financial burden among survivors. We are currently conducting a national randomized RCT to test two delivery modalities of HINT- synchronous, live, navigation sessions compared to an asynchronous, recorded, animated navigator sessions.

(Summary submitted by Elyse R Park, PhD, MPH, Tobacco Research & Treatment Center, Department of Psychiatry)

Rare Genetic Variant Exposes a Signaling Switch Required for Antifungal Immunity
Translational Genetics Identifies a Phosphorylation Switch in CARD9 Required for Innate Inflammatory Responses
Brandt M, Cao Z, Krishna C, Reedy JL, Gu X [et al.], Xavier RJ
Published in Cell Reports on 3/13/2024

Human genetic variants associated with disease offer opportunities to unravel underlying pathological processes. Dozens of variations in the CARD9 gene are linked with increased susceptibility to severe, potentially life-threatening fungal infections. CARD9 functions as a key mediator in inflammatory signaling pathways that respond to fungal infection. We leveraged a rare CARD9 variant to describe a switch in CARD9, mediated by a phosphorylation event, that is essential for its activity and subsequent immune responses against fungal infection. We further generated a mouse model of the CARD9 variant and showed that disruption of the switch impairs antifungal immunity in the skin.

(Summary submitted by Theresa Reimels, Division of Gastroenterology, Department of Medicine)

Preliminary Clinical Trial Results Show ‘Dramatic and Rapid’ Regression of Glioblastoma after Next Generation CAR-T Therapy
Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma
Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW [et al.], Maus MV
Published in New England Journal of Medicine on 3/13/2024 | Press Release

Our team is evaluating a new approach to CAR-T therapy for glioblastoma (GBM), engineering CAR-TEAM cells to treat mixed cell populations within tumors. Working in collaboration with Mass General neurosurgeons, we tested the approach in a phase 1 clinical trial of patients with recurrent GBM, and published the results for the first three patient cases. The trial, known as INCIPIENT, is designed to evaluate the safety of CARv3-TEAM-E T cells in patients with recurrent GBM. Just days after a single treatment, patients experienced dramatic reductions in their tumors, with one patient achieving near-complete tumor regression. In time, we observed tumor progression in these patients, but given the strategy’s promising preliminary results, we will pursue strategies to extend the durability of response.

(Summary submitted by Liz Murphy, MGB External Communications)

Using Machine Learning to Prevent Post-operative Complications
A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery
Beqari J, Powell J, Hurd J, Potter AL, McCarthy M [et al.], Li X
Published in Annals of Surgery on 3/14/2024

After cardiothoracic surgery, up to 32% of patients develop postoperative complications, many of which are serious and can be potentially life threatening. In this prospective pilot study, we evaluated whether machine learning analysis of high-resolution heart rate data, collected by wearable devices, could enable the early detection of postoperative complications—before symptom onset—after cardiothoracic surgery. We found that our machine learning algorithm detected 81% of postoperative complications a median of 2 days before symptom onset. These findings highlight the tremendous potential for machine learning algorithms, combined with wearable devices, to enable early postoperative complication detection even before symptom onset.

(Summary submitted by Chi-Fu Jeffrey Yang, MD, Department of Surgery)

Investigating Adherence to Neonatal Phototherapy Guidelines
Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline
Sarathy L, Chou JH, Romano-Clarke G, Darci KA, Lerou PH
Published in Pediatrics on 3/14/2024

In our study of over 22,000 newborns born at Mass General Brigham hospitals between January 2022 and June 2023, we observed a 47% decrease in babies receiving phototherapy for jaundice, and a 23% reduction in bilirubin blood tests following the American Academy of Pediatrics (AAP)’s updated clinical practice guideline for newborn jaundice. Meanwhile, the rate of bilirubin tests at pediatricians’ offices and newborns readmitted to the hospital for jaundice and did not change. These findings suggest that the new AAP guidelines can significantly decrease medical interventions without negative consequences.

(Summary submitted by Leela Sarathy, MD, Department of Pediatrics)

New Non-Invasive Test for Colorectal Cancer Screening
A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening
Chung DC, Gray DM 2nd, Singh H, Issaka RB, Raymond VM [et al.], Grady WM
Published in New England Journal of Medicine on 3/14/2024

Colorectal cancer remains the second leading cause of cancer-related deaths in the US, but only 59% of adults eligible for colorectal cancer screening are up to date. We tested the performance of a blood-based screening test that identifies tumor-specific changes in circulating DNA. In a cohort of 7861 average-risk individuals undergoing a colonoscopy, the test demonstrated sensitivity of 83% and specificity of 90%, which is comparable to other non-invasive screening tests. The sensitivity for advanced adenomatous polyps was 13%. Such a test may have an important impact on population health, as adherence to colorectal cancer screening is likely to improve with a blood-based approach.

(Summary submitted by Daniel C. Chung, MD, Division of Gastroenterology, Department of Medicine)

Studying the Genetic Risk for Psychosis and How Neurotransmitters Contribute
Association of Neurotransmitter Pathway Polygenic Risk with Specific Symptom Profiles in Psychosis
Warren TL, Tubbs JD, Lesh TA, Corona MB, Pakzad SS [et al.], Nord AS
Published in Molecular Psychiatry on 3/15/2024

Polygenic risk scores (PRS) are research tools that summarize someone’s genetic risk for a particular disease or trait. Most studies to date have focused on how well PRS can distinguish between people with and without a disease. Our study explores how PRS for specific biological pathways relate not only to risk for psychosis, but also several important clinical symptoms and outcomes. We found that psychosis patients with higher genetic risk related to dopamine (a major class of neurochemical signaling molecules targeted by current medications) tended to have worse functioning in their day-to-day lives. Importantly, we also found that PRS related to a different class of neurotransmitters, glutamate, was associated with worse cognitive performance, making this biological pathway a more promising target for future treatment development.

(Summary submitted by Justin D Tubbs, PhD, Center for Genomic Medicine, Department of Psychiatry)

Macrophages Role in Tissue Repair
Mechanosensing Regulates Tissue Repair Program in Macrophages
Meizlish ML, Kimura Y, Pope SD, Matta R, Kim C [et al.], Medzhitov R
Published in Science Advances on 3/15/2024

We set out to better understand how tissue repair is regulated and how dysregulated repair can lead to fibrosis, or scarring, in organs. Macrophages are immune cells that are famous for detecting microbes but also play an important role in regulating tissue biology, including repair. In this study, we found that macrophages can sense the extracellular matrix (ECM)—the structural elements of tissues—in order to regulate expression of genes involved in tissue repair. In particular, they sense tissues’ mechanical properties, like stiffness, which is known as mechanosensing. The big surprise was that macrophage mechanosensing works differently than other cells that are known to be mechanosensitive. Whereas other cells have to attach to the ECM and pull to sense its stiffness, macrophages appear to swim within the ECM and push against it, which we call “amoeboid” mechanosensing. Signals about the stiffness of the ECM are transmitted through changes in the cytoskeleton, the internal skeleton of the cell, which also incorporates other cues from the environment to shape how macrophages regulate tissue repair.

(Summary submitted by Matthew L Meizlish, MD, PhD, Department of Medicine)

Stem-immunity Hubs Associated with Response to Immunotherapy
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
Chen JH, Nieman LT, Spurrell M, Jorgji V, Elmelech L [et al.], Hacohen N
Published in Nature Immunology on 3/19/2024 | Research Spotlight

Harnessing the immune system to fight cancer has revolutionized medicine. We discovered the ‘immunity hub’, a group of immune cells that are organized in tumors and include T cells -- immune cells that kill tumors. Patients without immunity hubs in their tumors prior to cancer immunotherapy had poor outcomes relative to patients with hubs. We found that a subset of immunity hubs harbor special types of T cells that divide more efficiently and invigorate the antitumor immune response. These findings may help guide treatment decisions and elucidate targets for therapy to better direct immune cells to cure cancer.

(Summary submitted by Jonathan Chen, MD, PhD, Department of Pathology)

Mass General for Children Research Survey Finds Most Pediatricians Unprepared to Treat Teens with Opioid Use Disorder
Featuring Scott Hadland, MD, MPH

A nationwide survey of pediatricians found that slightly less than half felt prepared to counsel patients on opioid use disorder (OUD). Only 5% of pediatricians had ever prescribed standard of care OUD medications to their patients, despite rising rates of opioid-related overdose deaths among youths nationwide. The findings indicate a need for stronger OUD training throughout medical school and in continuing medical education programs, along with better incentives to treat patients with OUD, the team says.

Study Reveals Genetic Clusters and Biological Pathways That May Explain Differences in Type 2 Diabetes Risk
Featuring Miriam S. Udler, MD, PhD

Researchers have identified numerous genetic clusters that may help explain why people with type 2 diabetes have different clinical presentations. The identification of these genetic clusters points to a range of biological processes that likely contribute to the development of type 2 diabetes. The findings provide new insights into the biology of type 2 diabetes and could lead to novel strategies that tailor treatments for individual patients.

New Insights Into the Silencing of X Chromosome Genes Passed on From Fathers to Daughters
Featuring Jeannie T. Lee, MD, PhD and Chunyao Wei, PhD

Investigators have found that while some genes on the X chromosome passed from father to daughter become newly inactivated during embryo development, others are inherited from the father in a surprisingly pre-silenced state. These pre-suppressed genes tended to be the oldest in terms of their evolutionary age on the X-chromosome. The findings suggest a conserved mechanism whereby the paternal germline ensures that sons and daughters get the same “dose” of the X chromosome during development.

“Puffs Per Month” Provide a More Accurate Picture of Adolescents’ Exposure to Nicotine from E-cigarettes
Featuring Jonathan P. Winickoff, MD, MPH

Current measures that track youth e-cigarette use assess how many days in the past month individuals used e-cigarettes. A new study indicates that assessing the number of puffs of e-cigarettes taken per month provides a more accurate measure. Puffs per month had a stronger association with different measures of nicotine addiction, including greater cravings, less desire to quit, and fewer concerns about addiction.

Preliminary Clinical Trial Results Show ‘Dramatic and Rapid’ Regression of Glioblastoma after Next Generation CAR-T Therapy
Featuring Bryan Choi, MD, PhD, Marcela Maus, MD, PhD, and Elizabeth Gerstner, MD

Mass General Cancer Center researchers took a new approach to CAR-T, engineering CAR-TEAM cells to treat mixed cell populations within tumors. Working in collaboration with Mass General neurosurgeons, the team tested the approach in a phase 1 clinical trial of patients with recurrent glioblastoma. The first three patients in the trial showed dramatic responses within days.

Study Shows that United States and other Countries Can Do More to Improve Quality of Life for People with Down Syndrome
Featuring Brian Skotko, MD, MPP

An international group of investigators, led by researchers from Massachusetts General Hospital, conducted the first-ever survey to measure the quality of life of people with Down syndrome around the world. Responses from 50 countries were analyzed and each country was ranked on how well it supports people with Down syndrome across five domains of wellbeing. The U.S. ranked 13th of 45 countries in advocating for and supporting these individuals’ wellbeing.

World’s First Genetically-Edited Pig Kidney Transplant into Living Recipient Performed at Massachusetts General Hospital
Featuring Leonardo V. Riella, MD, PhD, Tatsuo Kawai, MD, PhD, Nahel Elias, MD and Winfred Williams, MD

Massachusetts General Hospital (MGH) announced the world’s first successful transplant of a genetically-edited pig (porcine) kidney into a 62-year-old man living with end-stage kidney disease (ESKD).

Aspirin Reduces Liver Fat in Clinical Trial of the Most Common Cause of Chronic Liver Disease
Featuring Andrew Chan, MD, MPH and Tracey Simon, MD

In a six-month phase 2 clinical trial of adults with metabolic dysfunction–associated steatotic liver disease, low-dose aspirin reduced average liver fat content by 10.2% compared with placebo. Aspirin also improved various markers of liver health related to inflammation and scarring.

Grade Study Investigators Publish Expanded Results of Major NIH-Sponsored Comparative Study of Glucose Lowering Medications in Type 2 Diabetes
Featuring David Nathan, MD and Deborah Wexler, MD

Ten new papers feature additional insights gleaned from a 2013-2021 study comparing four major medications approved to treat diabetes in combination with metformin. The current findings examine individual characteristics that were associated with the achievement of higher or lower average blood sugar levels over time. The results could help in identifying those who would benefit from more aggressive diabetes management.

Quantitative Analysis of Drug Tablet Aging
Conor Evans, PhD, an Associate Investigator at the Wellman Center for Photomedicine at Massachusetts General Hospital and Associate Professor at Harvard Medical School, is senior author of a new study in the journal Analyst, “Quantitative Analysis of Drug Tablet Aging by Fast Hyperspectral Raman Scattering Microscopy”.

Use of Artificial Intelligence in Improving Outcomes in Heart Disease
Antonis Armoundas, PhD, an associate investigator in the Cardiovascular Research Center at Massachusetts General Hospital and an associate professor of Medicine at Harvard Medical School, is the lead author of a new scientific statement from the American Heart Association, “Use of Artificial Intelligence in Improving Outcomes in Heart Disease”.

Entropy Removal of Medical Diagnostics
Shuhan He, MD, a physician investigator in the Department of Emergency Medicine and the Laboratory of Computer Science at Massachusetts General Hospital and an assistant professor of Medicine (Part time), at Harvard Medical School, is the lead author of a recent study published in Scientific Reports, “Entropy Removal of Medical Diagnostics”.

Nationwide Survey on Recovery Community Centers for Substance Use Disorder
Bettina B. Hoeppner, PhD, MS, director of the Health through Flourishing (HtF) Research Program in the department of psychiatry at Massachusetts General Hospital (MGH), core faculty member for the MGH Health Promotion and Resiliency Intervention Research (HPRIR) Center, and an associate professor of Psychology at Harvard Medical School is the first author of a recently published paper in the Journal of Addiction Medicine, “A Nationwide Survey Study of Recovery Community Centers Supporting People in Recovery from Substance Use Disorder”.

Cost-Effectiveness of Early Intervention: Treating Perinatally Acquired Hepatitis C Virus in 3-Year-Olds
Megan Rose Curtis, MD, and Andrea Ciaranello, MD, MPH, physician-investigators in the Division of Infectious Diseases at Massachusetts General Hospital, are co-authors of a recently published study in JAMA Pediatrics, “Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus”. Dr. Ciaranello is also the James and Audrey Foster MGH Research Scholar 2022-2027.

Stem-immunity Hubs Associated with Response to Immunotherapy
Jonathan Chen, MD, PhD, an investigator in the department of Pathology at Massachusetts General Hospital and Nir Hacohen, PhD, director of the Center of Cancer Immunology at Massachusetts General Hospital, are co-authors of a recently published study in Nature Immunology, “Human Lung Cancer Harbors Spatially-organized Stem-immunity Hubs Associated with Response to Immunotherapy”.

Enhancing Health Insurance Literacy in Childhood Cancer Survivors
Elyse R. Park, PhD, MPH an investigator in the Department of Psychiatry and Medicine at Massachusetts General Hospital, and Director of the Health Promotion Resiliency Intervention Research (HPRIR) Center, is the lead author of a recently published study in the Journal of Oncology Practice, “Health Insurance Navigation Tools Intervention: A Pilot Trial Within the Childhood Cancer Survivor Study”. Karen Kuhlthau, PhD, chief and director of General Academic Pediatrics at Mass General for Children, is senior author.

Frequency of Discordant Documentation of Patient Race and Ethnicity
Rama Salhi, MD, an investigator in the Department of Emergency Medicine at Massachusetts General Hospital, and an Assistant Professor of Emergency Medicine at Harvard Medical School, is the lead author of a recently published study in JAMA Network Open, “Frequency of Discordant Documentation of Patient Race and Ethnicity”.

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

Increase the sensitivity of liquid biopsies, neurons in the human brain able to predict what we're going to say before we say it and much more

Why Are More Young Adults Getting Colorectal Cancer? New Grant Will Support the Quest to Find Out
Featuring Andrew T. Chan, MD, MPH

Cancer Grand Challenges: Record £100m awarded to five teams taking on cancer’s toughest challenges, including Andrew Chan, MD, MPH, from Massachusetts General Hospital.

Mass General Researchers Share the Science of Sleep Health

Mass General researchers and clinicians share science-backed findings about the importance of sleep health.

The Astonishing Team Effort that Led to the First Trial of CAR T Cells for Glioblastoma at Mass General Brigham
Featuring Marcela Maus, MD, PhD and Bryan Choi, MD, PhD

It took contributions from almost 100 people to translate promising lab findings into a first-in-human treatment for glioblastoma.

Through the Magnifying Glass: The Faden Lab

How Daniel Faden, MD, and his team are working on developing and applying blood based cancer diagnostic tools.