Snapshot of Science for January 2024

Welcome to our Snapshot of Science for January 2024.

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: 

40 new studies published in high-impact journals, along with 32 summaries submitted by the research teams
7 new research-related press releases
12 research spotlights
12 posts from the Mass General Research Institute blog

Publications

New Understanding of Cognitive Changes in Aging
Spatiotemporal Correlation Between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging
Kim CM, Diez I, Bueichekú E, Ahn S, Montal V, Sepulcre J
Published in Journal of Neuroscience on 12/20/2023 | *Summary available

New Understanding of How Our Brain Combines Information from Different Senses
Visual Stimuli Modulate Local Field Potentials but Drive No High-frequency Activity in Human Auditory Cortex
Ahveninen J, Lee HJ, Yu HY, Lee CC, Chou CC [et al.], Lin FH
Published in Journal of Neuroscience on 12/21/2023 | *Summary available

Low Prenatal Maternal Fiber Intake May Increase Symptom Levels of ADHD in Childhood
Maternal Fiber Intake during Pregnancy and Development of Attention-Deficit/Hyperactivity Disorder Symptoms Across Childhood: The Norwegian Mother, Father and Child Cohort Study (MoBa)
Solberg BS, Kvalvik LG, Instanes JT, Hartman CA, Klungsøyr K [et al.], Zayats T
Published in Biological Psychiatry on 12/22/2023

Increase in Hospital-acquired Conditions in Hospitals after Private Equity Acquisition
Changes in Hospital Adverse Events and Patient Outcomes Associated With Private Equity Acquisition
Kannan S, Bruch JD, Song Z
Published in JAMA on 12/26/2023 | *Summary available

Causal Relationship Between the Financial Incentives and Physician Behavior
Urologist Practice Divestment from Radiation Vault Ownership and Treatment Patterns for Prostate Cancer
Faraj KS, Kaufman SR, Herrel LA, Maganty A, Oerline MK [et al.], Hollenbeck BK
Published in Cancer on 12/26/2023 | *Summary available

Micro-physiologic Evidence That Ripples May Bind Neural Activity Across Separated Cortical Regions
Co-occurring Ripple Oscillations Facilitate Neuronal Interactions Between Cortical Locations in Humans
Verzhbinsky IA, Rubin DB, Kajfez S, Bu Y, Kelemen JN [et al.], Halgren E
Published in PNAS on 12/29/2023

Women on Liver Transplant Waitlist Less Likely to Be Transplanted
Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40
Cron DC, Braun HJ, Ascher NL, Yeh H, Chang DC, Adler JT
Published in Annals of Surgery on 1/1/2024 | *Summary available

New Approach for 'Single Cell Surgery'
High Throughput Intracellular Delivery by Viscoelastic Mechanoporation
Sevenler D, Toner M
Published in Nature Communications on 1/2/2024 | *Summary available

Six Proteins Identified as Potential Targets to Prevent or Treat HDPs
Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia
Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW [et al.], Honigberg MC
Published in JAMA Cardiology on 1/3/2024 | *Summary available | Press Release

Potential Therapeutic Targets for Conditions with TDP-43 Proteinopathy
Cryptic Splicing of Stathmin-2 and UNC13A mRNAs is a Pathological Hallmark of TDP-43-associated Alzheimer's Disease
Agra Almeida Quadros AR, Li Z, Wang X, Ndayambaje IS, Aryal S [et al.], Lagier-Tourenne C
Published in Acta Neuropathologica on 1/4/2024 | *Summary available

Critical Tissue-Specific Networks Underlying Familial Dysautonomia
Transcriptome Analysis in a Humanized Mouse Model of Familial Dysautonomia Reveals Tissue-specific Gene Expression Disruption in the Peripheral Nervous System
Harripaul R, Morini E, Salani M, Logan E, Kirchner E [et al.], Slaugenhaupt S
Published in Scientific Reports on 1/4/2024

Utilizing Helical Reconstruction Techniques to Study VP39 structure
Helical Reconstruction of VP39 Reveals Principles for Baculovirus Nucleocapsid Assembly
Benning FMC, Jenni S, Garcia CY, Nguyen TH, Zhang X, Chao LH
Published in Nature Communications on 1/4/2024 | *Summary available

New Genetic Link Between Anorexia Nervosa and Being an Early Riser
The Role of Circadian Rhythms and Sleep in Anorexia Nervosa
Wilcox H, Paz V, Saxena R, Winkelman JW, Garfield V, Dashti HS
Published in JAMA Network Open on 1/4/2024 | *Summary available | Press Release

Bacterial Strain Identified that Demonstrates a Potentially Protective Role in Celiac Disease
Novel Bacteroides Vulgatus Strain Protects against Gluten-induced Break of Human Celiac Gut Epithelial Homeostasis: A Pre-clinical Proof-of-concept Study
Tran T, Senger S, Baldassarre M, Brosnan RA [et al.], Fasano A; CDGEMM Team
Published in Pediatric Research on 1/4/2024 | *Summary available | Press Release

Acquired Resistance to FGFR Inhibition
Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma
Wu Q, Ellis H, Siravegna G, Michel AG, Norden BL [et al.], Bardeesy N
Published in Clinical Cancer Research on 1/5/2024

DF-3D Biofabrication of Off-the-Shelf Human Tissue Analogs
DeepFreeze 3D-biofabrication for Bioengineering and Storage of Stem Cells in Thick and Large-Scale Human Tissue Analogs
Kumar A, Brown RA, Roufaeil DB, Gupta A, Lipford EL [et al.], Zalzman M
Published in Advanced Science on 1/6/2024 | *Summary available

Cellular Pathogenesis in Friedreich's Ataxia
METTL17 is an Fe-S cluster Checkpoint for Mitochondrial Translation
Ast T, Itoh Y, Sadre S, McCoy JG, Namkoong G [et al.], Mootha VK
Published in Molecular Cell on 1/9/2024

Antenatal Steriod Administration for Late Preterm Births
Regional Variation in Antenatal Late Preterm Steroid Use Following the ALPS Trial
Freret TS, Cohen JL, Gyamfi-Bannerman C, Kaimal AJ, Lorch SA [et al.], Clapp MA
Published in JAMA Network Open on 1/9/2024 | *Summary available

Improving Early Detection of Axonal Damage for MS
A Translational MRI Approach to Validate Acute Axonal Damage Detection as an Early Event in Multiple Sclerosis
Cerdán Cerdá A, Toschi N, Treaba CA, Barletta V, Herranz E [et al.], De Santis S
Published in eLife on 1/9/2024 | *Summary available

Predicting Single Cell Gene Expression from Images Through AI
Prediction of Single-cell RNA Expression Profiles in Live Cells by Raman Microscopy with Raman2RNA
Kobayashi-Kirschvink KJ, Comiter CS, Gaddam S, Joren T, Grody EI [et al.], Regev A
Published in Nature Biotechnology on 1/10/2024 | *Summary available | Research Spotlight

Lack of Free-Time Exercise Significantly Increases Risk of Cardiac Death
Lack of Leisure Time Physical Activity and Variations in Cardiovascular Mortality across US Communities: A Comprehensive County-level Analysis (2011-2019)
Abohashem S, Nasir K, Munir M, Sayed A, Aldosoky W [et al.], Rana JS
Published in British Journal of Sports Medicine on 1/10/2024 | *Summary available | Press Release

Impact of Transportation Insecurity on Patients with Chronic Liver Disease
Health Care-related Transportation Insecurity is Associated with Adverse Health Outcomes Among Adults with Chronic Liver Disease
Ufere NN, Lago-Hernandez C, Alejandro-Soto A, Walker T, Li L [et al.], Serper M
Published in Hepatology Communications on 1/11/2024 | *Summary available | Research Spotlight

Hypoxia-driven Rescue of Mitochondrial Disease
Hypoxia and Intra-complex Genetic Suppressors Rescue Complex I Mutants by a Shared Mechanism
Meisel JD, Miranda M, Skinner OS, Wiesenthal PP [et al.], Ruvkun G, Mootha VK
Published in Cell on 1/11/2024 | *Summary available

Microbiome Contributes to Disease-associated Metabolite Changes
Linking Microbial Genes to Plasma and Stool Metabolites Uncovers Host-microbial Interactions Underlying Ulcerative Colitis Disease Course
Schirmer M, Stražar M, Avila-Pacheco J, Rojas-Tapias DF, Brown EM [et al.], Xavier RJ
Published in Cell Host Microbe on 1/11/2024 | *Summary available

A Future Target for Pharmaceutical Antibodies and Vaccine Design
Antibody Production Relies on the tRNA Inosine Wobble Modification to Meet Biased Codon Demand
Giguère S, Wang X, Huber S, Xu L, Warner J [et al.], Batista FD
Published in Science on 1/11/2024 | *Summary available

Interventions to Decrease Dosing Errors in Pediatric ED Patients
Analysis of a Medication Safety Intervention in the Pediatric Emergency Department
Samuels-Kalow ME, Tassone R, Manning W, Cash R, Davila-Parrilla L [et al.], Camargo CA Jr
Published in JAMA Network Open on 1/12/2024 | *Summary available

A New Technique to Improve Postoperative Sensitivity After Double Mastectomy
Prospective Sensory Outcomes for Targeted Nipple Areola Complex Reinnervation (TNR) in Gender-Affirming Double Incision Mastectomy with Free Nipple Grafting
Remy K, Packowski K, Alston C, Kozanno LN, Carruthers KH [et al.], Gfrerer L
Published in Annals of Surgery on 1/12/2024 | *Summary available

The Potential of Quantified Entropy Removal in Medical Diagnostic Decision Making
Entropy Removal of Medical Diagnostics
He S, Chong P, Yoon BJ, Chung PH, Chen D, Marzouk S, Black KC, Sharp W, Safari P, Goldstein JN, Raja AS, Lee J
Published in Scientific Reports on 1/12/2024 | *Summary available

Understanding Mitochondrial Ultrastructure and Cellular Function
In situ Architecture of Opa1-dependent Mitochondrial cristae Remodeling
Fry MY, Navarro PP, Hakim P, Ananda VY, Qin X [et al.], Chao LH
Published in The EMBO Journal on 1/15/2024 | *Summary available

Expanding the Capabilities of Stereotactically Placed Electrodes
Flexible, Scalable, High Channel Count Stereo-electrode for Recording in the Human Brain
Lee K, Paulk AC, Ro YG, Cleary DR, Tonsfeldt KJ [et al.], Dayeh SA
Published in Nature Communications on 1/17/2024 | *Summary available

Diagnosing Pancreatic Serous Cystadenoma
Pancreatic Serous Cystadenoma: A Continuing Diagnostic Challenge
Assawasirisin C, Qadan M, Aimprasittichai S, Kambadakone A, Servin-Rojas M [et al.], Fernández-Del Castillo C
Published in Annals of Surgery on 1/17/2024

Combination Therapy for Brain Metastasis Shows Promise
CDK4/6 Inhibition Sensitizes Intracranial Tumors to PD-1 Blockade in Preclinical Models of Brain Metastasis
Nayyar N, de Sauvage MA, Chuprin J, Sullivan EM, Singh M [et al.], Brastianos PK
Published in Clinical Cancer Research on 1/17/2024 | *Summary available

Newly Characterized Form of Tau May Be Involved in initiating Alzheimer’s Disease
Alzheimer Proteopathic Tau Seeds are Biochemically a Forme Fruste of Mature Paired Helical Filaments
Kumar M, Quittot N, Dujardin S, Schlaffner CN, Viode A [et al.], Hyman BT
Published in Brain on 1/18/2024 | *Summary available | Press Release

Learning More About a Driver of Mutagenesis in Cancer
APOBEC3A Induces DNA Gaps through PRIMPOL and Confers Gap-associated Therapeutic Vulnerability
Kawale AS, Ran X, Patel PS, Saxena S, Lawrence MS, Zou L
Published in Science Advances on 1/19/2024 | *Summary available

How Often Older Adults Get Medical Care Outside the Home
Health Care Contact Days Among Older Adults in Traditional Medicare : A Cross-Sectional Study
Ganguli I, Chant ED, Orav EJ, Mehrotra A, Ritchie CS
Published in Annals of Internal Medicine on 1/23/2024

Implementation Strategies for a Pediatric Weight Management Program
Evaluating the Implementation of the Connect for Health Pediatric Weight Management Program
Simione M, Frost HM, Farrar-Muir H, Luo M, Granadeño J, Torres C, Boudreau AA, Moreland J, Wallace J, Young J, Orav J, Sease K, Hambidge SJ, Taveras EM
Published in JAMA Network Open on 1/25/2024 | *Summary available

TET2 CHIP is a Risk Factor for Incident HFpEF
Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction
Schuermans A, Honigberg MC, Raffield LM, Yu B, Roberts MB, Kooperberg C, Desai P, Carson AP, Shah AM, Ballantyne CM, Bick AG, Natarajan P, Manson JE, Whitsel EA, Eaton CB, Reiner AP
Published in JAMA Network Open on 1/25/2024

Modeling the Health Impact of Proposed Policies to Redistribute Wealth
Wealth Redistribution to Extend Longevity in the US
Himmelstein KEW, Tsai AC, Venkataramani AS
Published in JAMA Internal Medicine on 1/29/2024 | *Summary available | Research Spotlight

Machine-Learning Models to Support Funding Decisions for Medical Research
Impact of Medical Technologies May Be Predicted Using Constructed Graph Bibliometrics
Jiang L, Raza A, El Ariss AB, Chen D, Danaher-Garcia N, Lee J, He S.
Published in Scientific Reports on 1/29/2024 | *Summary available

“Promotion in Place” Pilot Promotes Competency-based Medical Education
Promotion in Place: A Model for Competency-Based, Time-Variable Graduate Medical Education
Goldhamer MEJ, Pusic MV, Nadel ES, Co JPT, Weinstein DF
Published in Academic Medicine on 1/29/2024 | *Summary available

Publication Summaries

It is poorly known how amyloid beta (Aβ) and tau associate at the spatiotemporal level in the brain to impact cognitive changes in older adults. We used a graph theory-based spatiotemporal analysis to characterize the cortical patterns of Aβ and tau deposits and their relationship with cognitive changes in an aging cohort. We found that the temporal accumulations of interlinked Aβ and tau pathology at the network level display distinctive spatiotemporal associations with early cognitive decline. Our results revealed the multifaceted spatiotemporal connectomics of tau-Aβ pathology is a critical contributor to clinical trajectories toward AD in older adults.

(Summary submitted by Chanmie Kim, PhD, Gordon Center for Medical Imaging, Department of Radiology)

New Understanding How Our Brain Combines Information from Different Senses
Visual Stimuli Modulate Local Field Potentials but Drive No High-frequency Activity in Human Auditory Cortex
Ahveninen J, Lee HJ, Yu HY, Lee CC, Chou CC [et al.], Lin FH
Published in Journal of Neuroscience on 12/21/2023

Visual information influences how we hear sounds, especially in noisy settings. These "cross-sensory" influences start already in auditory cortices, the brain area that processes sound signals. Whether the auditory cortex actively deals with visual information or if visual signals simply change how we process sounds is not fully clear. We investigated this by recording brain activity from 16 people with epilepsy who had electrodes implanted in their brain for medical reasons. Using these recordings, conducted in collaboration with Taipei Veterans General Hospital in Taipei, Taiwan, we found that visual information affects how we process sounds, but it doesn't cause high-frequency brain activity in the auditory cortex, which is a signal of local neuronal firing. This finding helps us better understand how our brain combines information from different senses.

(Summary submitted by Jyrki Ahveninen, PhD, Martinos Center for Biomedical Imaging, Department of Radiology)

Private equity firms have increasingly acquired U.S. hospitals, including in Massachusetts. The classic private equity model uses substantial debt to finance acquisitions and generates returns for investors over a short horizon. The impact of this form of ownership on quality of hospital care had been largely unknown. In 662,095 hospitalizations at 51 private equity hospitals, private equity acquisition was associated with a 25.4% increase in hospital-acquired conditions, which was driven by central line–associated bloodstream infections and falls relative to 4,160,720 hospitalizations at 259 matched control hospitals. Medicare beneficiaries treated at private equity hospitals were younger and less likely to be dually eligible for Medicaid, likely reflecting a lower-risk population of admitted beneficiaries. The increase in hospital-acquired adverse events, despite a likely healthier cohort of admitted Medicare beneficiaries, suggests poorer quality of inpatient care.

(Summary submitted by Sneha Kannan, MD, Department of Medicine)

Urology practices that owned radiation vaults and subsequently divested from ownership were less likely to treat patients for prostate cancer. The decline in treatment was most pronounced in men who were least likely to benefit from treatment (i.e., those who would potentially be overtreated). These findings lend support to the causal relationship between the financial incentives and physician behavior. This study has important implications for healthcare reform. It suggests that condition-based payment models that incentivize constraint on utilization may be effective in offsetting the financial incentives associated with treatment that are inherent with radiation vault ownership.

(Summary submitted by Kassem Faraj, MD, University of Michigan)

Women on the liver transplant waitlist are less likely to be transplanted compared to men. In response, the disease severity score (MELD), which determines priority for liver transplant, recently changed to account for sex. It is unclear if this change will be sufficient to eliminate this disparity. We examined a large cohort of patients with the same MELD score (40—the highest possible score), and women were still 10% less likely to be transplanted and 14% more likely to die/be removed from the waitlist compared to men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

(Summary submitted by David C Cron, MD, MS, Department of Surgery)

New Approach for 'Single Cell Surgery'
High Throughput Intracellular Delivery by Viscoelastic Mechanoporation
Sevenler D, Toner M
Published in Nature Communications on 1/2/2024

Manufacturing cell therapies such as CAR T requires the genetic modification of hundreds of millions of cells for each dose. Currently, genetic modification is performed using engineered viruses, but these have safety concerns and are also incompatible with more precise approaches based on CRISPR technology. We developed a microfluidic device that exposes cells to a sub-millisecond pulse of stretching forces, creating pores in the cell membrane that allow new genes and CRISPR systems to enter the cell and then reseal within seconds. Importantly, we also showed our approach to 'single cell surgery' has sufficient throughput that scaling to production volumes is feasible.

(Summary submitted by Derin Sevenler, PhD, Center for Engineering in Medicine & Surgery, Department of Surgery)

Despite substantial global impact of the hypertensive disorders of pregnancy (HDPs, e.g., preeclampsia, gestational hypertension) on maternal and offspring health, the biology of these conditions remains incompletely understood. In our study, we tested whether genetically predicted levels of cardiovascular-related proteins in the bloodstream influenced the risk of developing HDPs. We identified 6 proteins with strong evidence of causal or protective roles, including eosinophil cationic protein, heat shock protein 27, and NT-proBNP. These proteins represent potential targets to prevent or treat HDPs and warrant further investigation in animal and human studies.

(Summary submitted by Michael C Honigberg, MD, MPP, Cardiovascular Research Center, Division of Cardiology, Department of Medicine)

Alzheimer's disease is characterized by harmful protein buildup in the brain, causing neurodegeneration. A key protein, TDP-43, abnormally accumulates in about half of Alzheimer's cases, which affects TDP43 normal function. Recently, we and others, found that two vital proteins for brain cell function, Stathmin-2 and UNC13A, are reduced in cells with abnormal TDP-43 localization. In this study, we show that Stathmin-2 and UNC13A, undergo changes specifically in Alzheimer’s patients with abnormal TDP-43. This insight opens possibilities for future treatments targeting these protein alterations, offering a new approach to manage and diagnose Alzheimer’s disease.

(Summary submitted by Clotilde Lagier-Tourenne MD, PhD, Department of Neurology)

Helical Reconstruction of VP39 Reveals Principles for Baculovirus Nucleocapsid Assembly
Benning FMC, Jenni S, Garcia CY, Nguyen TH, Zhang X, Chao LH
Published in Nature Communications on 1/4/2024

Viruses are experts in attacking organisms. To protect their genome, which contains the blueprint for making all tools needed for host infection, viruses build a protein cage (a nucleocapsid) around it. We discovered the architecture of an insect virus (baculovirus) nucleocapsid, by using an electron microscope, which unlike light microscopes, enables us to see the tiny protein machines of a cell. Like a LEGO model, our structure explains how the nucleocapsid is built. This will help to improve the properties of baculoviruses, which are used to produce vaccines, for therapeutic gene delivery in some cancers and as safe biological pesticides.

(Summary submitted by Friederike M C Benning, PhD, Department of Molecular Biology)

What is the relationship between anorexia nervosa, circadian rhythms, and sleep traits? Findings: In this genetic association study, the investigators found a bidirectional causal relationship between anorexia nervosa and morning chronotype using Mendelian randomization. In addition, they found an association between anorexia nervosa and insomnia using both Mendelian randomization and a polygenic risk score for anorexia nervosa in the MGB Biobank. Meaning: These findings implicate anorexia nervosa as a morningness eating disorder in contrast to most other evening-based psychiatric and eating diseases and corroborate the association between anorexia nervosa and insomnia observed in earlier observational studies.

(Summary submitted by Hassan S Dashti, PhD, RD, Department of Anesthesia, Critical Care and Pain Medicine)

After more than ten years of research, a team of celiac disease scientists has identified a strain of Bacteroides vulgatus that may provide protection against the break of tolerance to gluten that occurs in the early stages of celiac disease autoimmunity. After collecting thousands of data points in the Celiac Disease Genomic, Environmental, Microbiome and Metabolomic Study from approximately 600 infants and children, researchers used deep genomic analysis to identify several bacterial strains for further study. The scientists introduced B. vulgatus into gluten-treated gut organoids, resulting in decreased intestinal permeability, inflammatory cytokines and cell death.

(Summary submitted by Susie Flaherty, MA, ATR. The Center for Celiac Research and Treatment and The Mucosal Immunology and Biology Research Center, Mass General Hospital for Children)

The creation of 3D scaffolds that mimic the structure of biological tissues is highly appealing. Current techniques are limited by their complexity, low cell survival, and slow printing speed. While at the University of Maryland School of Medicine, Dr. Alok Kumar, currently an Instructor at the CVRC at the MGH, and his colleagues developed a new approach that involved 3D bioprinting the biomaterial at subzero temperatures. Dr. Kumar and his colleagues developed a novel bioink, which protected the cells at low temperatures and was also suited for 3D bioprinting.

(Summary submitted by Alok Kumar, MSc, MS, PhD, Cardiovascular Research Center, Divsion of Cardiology, Department of Medicine)

Antenatal Steroid Administration for Late Preterm Births
Regional Variation in Antenatal Late Preterm Steroid Use Following the ALPS Trial
Freret TS, Cohen JL, Gyamfi-Bannerman C, Kaimal AJ, Lorch SA [et al.], Clapp MA
Published in JAMA Network Open on 1/9/2024

The ALPS Trial demonstrated that antenatal steroid administration during the late preterm period reduces neonatal respiratory morbidity, a common complication of prematurity. In this study, the authors show that despite the dissemination of high-quality evidence and support from obstetric professional societies, the practice of administering antenatal steroids to patients at risk for a late preterm birth was not uniformly adopted across the US. These findings should catalyze future studies on the causes for regional variation in steroid use and, more broadly, on the barriers and facilitators to incorporating new evidence-based guidelines into clinical practice.

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

We, in collaboration with the Institute for Neurosciences in Alicante, Spain, have developed and translated a novel, non-invasive, magnetic resonance imaging (MRI) technique based on water diffusion to detect axonal degeneration in the early stages of multiple sclerosis. Multiple sclerosis is a chronic neurological disease that affects millions of people worldwide. In multiple sclerosis, axons, the extensions of nerve cells that transmit electrical signals within the brain, often degenerate, and this may lead to permanent disability. The results of this study open the way to the search for new treatments focused on reversing axonal damage in multiple sclerosis. The technique could be also applied in other diseases, for example brain trauma, which may be associated with axonal damage.

(Summary submitted by Caterina Mainero, MD, PhD, Martinos Center for Biomedical Imaging, Department of Radiology)

The advent of sequencing technologies has undoubtedly been transformative in unraveling the complexity of disease heterogeneity, dynamics, and progression. However, sequencing technologies are expensive and destroy the cell, precluding us from tracking the temporal dynamics of live cells in tissues and humans. We have developed one of the first technologies that will allow us to query and predict single-cell genomics information from images using AI at a low cost, non-destructively in live cells, and at a large scale. This groundbreaking approach holds significant promise for understanding gene regulation, diagnosing diseases, and facilitating drug discovery.

(Summary submitted by Jian Shu, PhD, Cutaneous Biology Research Center, Department of Dermatology)

Heart disease is the leading cause of death worldwide and among U.S. Adults. In this study, we compiled data from the CDC to study the reasons behind this risk across different U.S. populations, with a particular focus on community-wide leisure-time physical inactivity (LTPI). We analyzed over 7 million cardiac deaths across 2900 US counties, covering about 310 million residents, from 2011 to 2019. We discovered a concerning pattern: even though there's been a national decrease in heart disease deaths, regions with high levels of adults not exercising in their free time continue to see higher mortality rates beyond the effect of other social determinants of health. Concerningly, two groups of people, namely middle-aged women, and elderly Blacks, were disproportionately affected more than others. Further, the study also uncovered that contextual factors like socioeconomic conditions and the prevalence of chronic diseases can explain up to 65% of these high LTPI rates. These findings underscore the need for multi-level public health strategies that address both individual behavior and broader societal factors to promote exercising and reduce heart disease

(Summary submitted by Shady Abohashem , MD, MPH, Cardiovascular Research Center, Cardiology Division, Department of Medicine)

In a national survey study of U.S. adults, patients with chronic liver disease who answered "Yes" to the question “Have you delayed getting care in the past 12 months because you did not have transportation?” had a higher likelihood of having increased acute health care use and mortality. Health care-related transportation insecurity is a critical social risk factor for U.S. adults with chronic liver disease, and there is an urgent need for feasible and scalable interventions, clinical programs, and policy reform to address transportation barriers and improve their clinical outcomes.

(Summary submitted by Nneka N. Ufere, MD MSCE, Division of Gastroenterology, Department of Medicine)

Previous research has shown that mice with electron transport chain (ETC) complex I dysfunction are rescued by hypoxia (low oxygen). We show that hypoxia rescue of complex I deficiency is evolutionarily conserved to Caenorhabditis elegans. To uncover the mechanism, we used C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6 that mimic the action of hypoxia. Using additional genetic screens, we found evidence for acute hypoxia rescuing complex I activity via changes in the ubiquinone binding pocket, providing potential therapeutic insights for mitochondrial diseases related to ETC dysfunction.

(Summary submitted by Joshua D Meisel, PhD, Department of Molecular Biology)

Understanding microbial contributions to inflammatory diseases requires identification of effector molecules. To uncover host-microbial interactions across the disease severity spectrum in ulcerative colitis (UC), we integrated paired metagenomics, stool and plasma metabolomics from the PROTECT pediatric UC cohort. Severe disease-associated microbial changes included an increase in oral-colonizing bacteria, such as Veillonella parvula; metabolite changes included dipeptides and bile acids in stool and polyamines in plasma. Using culturomics, we demonstrated that V. parvula produces immunomodulatory tryptophan metabolites and metabolizes immunosuppressive thiopurine drugs. Our approach establishes a framework for linking microbes to metabolite changes in disease pathology with implications for therapeutic efficacy.

(Summary submitted by Heather Kang, PhD, Broad Institute)

Antibodies are proteins produced in great quantities to prevent infection. Protein production is powered by small molecules called transfer RNAs (tRNA). A specific tRNA binds a matching “codon” sequence in messenger RNA (mRNA) to add the next puzzle piece to the growing protein. We found that antibodies are heavily reliant on codons with no corresponding tRNAs encoded in the genome: they rely on a post-transcriptional modification called inosine, which allows “wobble”translation of a specific near-match. Understanding the tRNA requirements of antibodies could change the way we design vaccines and antibody-based therapeutics.

(Summary submitted by Stephanie R. Weldon, PhD, Ragon Institute)

Acetaminophen and ibuprofen are commonly used medications in children, but families struggle to dose them accurately at home. A randomized clinical trial previously showed that the Medication Education for Dosing Safety (MEDS) intervention (consisting of a simplified handout, dosing syringe, dose demonstration and teach-back) was associated with reduced rates of parental dosing error at home. In the current study, a mixed-method interrupted time series study in an academic pediatric emergency department (ED), MEDS training for clinicians was associated with decreased risk of error and this improvement was sustained after the intervention concluded. The findings suggest that attempts to develop simplified, brief interventions are associated with improved medication safety for children after discharge from the ED.

(Summary submitted by Margaret E Samuels-Kalow, MD, MPhil, MSHP, Department of Emergency Medicine)

Gender-affirming mastectomy (GAM) is an important step for patients transitioning from female to male. However, many patients may suffer from loss of feeling at the nipple-areola complex (NAC) and chest after surgery. Nerve preservation and reconstruction using Targeted NAC Reinnervation (TNR) has the potential to improve sensation after surgery. We evaluated the sensory outcomes of 25 patients undergoing GAM with TNR. Various sensory functions were preserved as soon as 3 months postoperatively, including quantitative tactile sensation, as well as qualitative tactile, pressure, temperature and erogenous sensation. Therefore, TNR is a possible solution to preserve feeling in patients undergoing chest surgery.

(Summary submitted by Katya Remy, MD, Department of Surgery)

This research paper presents a novel approach to evaluating medical diagnostic tools using Shannon entropy, a measure of uncertainty in information theory. The study analyzed 623 medical decision-making tools, demonstrating that entropy removal correlates with traditional diagnostic metrics like sensitivity and specificity. It offers a new perspective on assessing the effectiveness of diagnostics, particularly in emergency medicine, where accurate and timely decision-making is critical. The methodology emphasizes the potential of entropy reduction as a tool for healthcare innovation and improvement in patient outcomes.

(Summary submitted by Shuhan He, MD, Laboratory of Computer Science)

We used advanced imaging, called electron cryo-tomography, to study the architecture of mitochondria in cells. Mitochondria are double-walled cellular sub-compartments that house many essential reactions in membrane folds, called cristae. We describe how the imbalance of two forms of the protein Opa1 influences cristae shape. High level of the long unprocessed form of Opa1 lead to stacked cristae and elongated mitochondria, while increased levels of a short, processed form of Opa1 resulted in irregular cristae packing. This imbalance impacted programmed cell death, calcium handling, and respiratory function. This study illuminates the connection between mitochondrial structure and function, critical for understanding cellular health and energy production.

(Summary submitted by Michelle Y Fry, PhD, Department of Molecular Biology)

Recording directly from the brain with electrodes can be crucial for understanding and diagnosing brain disorders such as epilepsy and cancer and uncovering the basics of cognition, though, for decades, the technology has largely remained rigid or even hand-made in the case of human brain recordings. Here, we demonstrate a novel, scalable manufacturing approach to produce a thin-film penetrating electrode which produces less damage to brain tissue. We demonstrate the recording and stimulation capabilities of this highly flexible electrode in four different species, including humans, opening up a massive number of possibilities for longer-term recordings and stimulation for neurotherapeutic uses.

(Summary submitted by Angelique C Paulk, PhD, Department of Neurology)

Patients with brain metastatic cancer have limited treatment options. Metastatic brain tumors frequently fail cancer immunotherapy treatment since immune responses within the brain are tightly regulated. We found that pharmacologically blocking CDK4 and CDK6, which drive cell growth and division, can boost cancer immunity within the brain by reducing immune suppression and improving T cell function. When combined with immunotherapy targeting PD-1, CDK4/6 inhibitor abemaciclib reduced tumor growth both inside and outside the brain and improved survival in animal models of brain metastasis. Our findings suggest that combined treatment with CDK4/6 and PD-1 inhibitors is a promising therapeutic approach for patients with brain metastases.

(Summary submitted by Naema Nayyar, Mass General Cancer Center)

In studies of the brains of patients with Alzheimer’s disease, we found a soluble form of tau that is not present in classic tau aggregates but has the same toxic properties. We used advanced methods including mass spectroscopy, to learn about the first steps in how that protein accumulates and aggregates. The tau protein accumulates in the brains of patients with Alzheimer disease in neurons that are destined to die. This suggests that the soluble tau may be an earlier step in the process that ultimately leads to neurodegeneration. More research is needed to understand this form of tau and explore new strategies to block it.

(Summary submitted by Bradley T. Hyman, MD, PhD, Department of Neurology)

APOBEC3A cytidine deaminase is implied as a mutagenic driver during cancer formation and tumor evolution allowing cancer to evade targeted therapy. Hence, it is important to identify ways to eliminate tumor cells expressing APOBEC3A. We found that APOBEC3A expression induces a unique form of DNA replication stress by increasing the single-stranded gaps in DNA. APOBEC3A-induced ssDNA gaps are repaired by action of ATR kinase and PARP. Inhibition of these proteins accumulates ssDNA gaps which lead to preferentially killing of A3A+ cells. Thus, APOBEC3A-induced replication stress arises from ssDNA gaps, which confer a therapeutic vulnerability to gap-targeted DNA repair inhibitors.

(Summary submitted by Ajinkya S Kawale, PhD, Mass General Cancer Center)

We studied what implementation strategies would help pediatric primary care practices adopt a healthy lifestyle program. In this study of 18,333 children at three US healthcare organizations, we found implementation strategies to be effective in promoting program adoption and equitable reach. The program was highly acceptable by clinicians, well-liked by families, and determined to have factors that would support program sustainability. Our findings suggest that understanding how to implement programs in primary care will increase the uptake of evidence-based programs for children with overweight and obesity.

(Summary submitted by Meg Simione, PhD, Department of Pediatrics)

We found that Americans’ life expectancy varies greatly with wealth; among middle-aged adults, the wealthiest individuals survive 13.5 years longer than the poorest individuals. Fully equalizing household wealth could increase longevity at midlife by 2.2 years overall, with the greatest benefits for the poorest Americans -- an 8.8 year increase in life expectancy at midlife, on average, with no tradeoffs in life expectancy among wealthier individuals. We also modelled the population health impacts of recently proposed policies, such as the “baby bonds” to give grants to American children. We predicted that baby bonds could increase overall American life expectancy at midlife by 1 year, and could increase longevity for the poorest Americans by 6.4 years. We found that White Americans would gain 1.7 years of life expectancy at midlife, while Black Americans would gain 4 years. Overall, our findings suggest that policies to redistribute wealth in the United States could improve health and longevity, and could narrow the racial mortality gap.

(Summary submitted by Kathryn Himmelstein, MD, Division of Infectious Diseases, Department of Medicine)

This study introduces a novel method of using machine learning for predicting the impact of medical technologies. By mapping scientific publications into a network graph, it clearly demonstrates the interconnections and influences among various medical technologies and research areas. This graphical machine learning approach aids in identifying emerging trends and potential future developments in healthcare, providing a valuable tool for strategic decision-making. The paper is the first step into creating a "copilot" tool for human research grant funding decision makers.

(Summary submitted by Shuhan He, MD, Laboratory of Computer Science)

Competency-based medical education is increasingly regarded as a preferred framework for physician training, though few projects exist in the United States. In an Academic Medicine paper, “Promotion in Place: A Model for Competency-Based, Time-Variable Graduate Medical Education”, available through open access, the authors describe a vision for CBTV-GME and an implementation model that can be applied across specialties. The “Promotion in Place” (PIP) model relies on enhanced assessment, clear criteria for advancement, and flexibility to adjust individuals’ responsibilities and time-in-training based on demonstrated competence. Implementation templates and guides are included as a roadmap for programs interested in piloting CBTV- GME. This pilot is funded by a $2M American Medical Association Reimagining Residency grant to the Mass General Brigham Office of Graduate Medical Education.

Press Releases

Scientists Solve Mystery of How a Rare Congenital Scalp Defect Forms
Featuring Alexander Marneros, MD, PhD

Researchers have revealed the mechanisms behind mutations that cause a congenital condition called aplasia cutis congenita, in which babies are born without skin along the midline of the scalp. The mutations lead to the impairment of cells that normally express growth factors that induce skin formation over the skull.

Researchers Identify Circulating Proteins Linked to Preeclampsia and Other Hypertensive Disorders of Pregnancy
Featuring Michael C. Honigberg, MD, MPP

Investigators have identified proteins circulating in the blood that likely contribute to or protect against the development of preeclampsia and other hypertensive disorders of pregnancy.. Treatment options for these conditions (other than delivery) remain limited. Therapies that target these proteins might help to prevent or treat these conditions.

Study Reveals New Genetic Link Between Anorexia Nervosa and Being an Early Riser
Featuring Hassan S Dashti, PhD, RD

Investigators have discovered that anorexia nervosa is associated with morning chronotype, or a propensity for earlier sleep and activity timing. They also observed a relationship between the eating disorder and insomnia. The findings could direct future investigations into circadian- and sleep-based therapies for anorexia nervosa.

Study Shows that Lack of Free-Time Exercise Significantly Increases Risk of Cardiac Death
Featuring Shady Abohashem, MD, MPH

An analysis of countrywide CDC data showed that adults who fail to exercise in their free time have significantly higher rates of death from cardiovascular disease, beyond other social determinants. Middle-aged women and elderly Black individuals are among those with the highest risk. New interventions that improve access to exercise opportunities and information about the importance of exercise are needed, the researchers say.

Researchers at Mass General for Children Identify a Bacterial Strain that Demonstrates a Potentially Protective Role in Celiac Disease
Featuring Alessio Fasano, MD

Researchers from Mass General for Children (MGfC) and 13 other institutions have identified a strain of Bacteroides vulgatus that may protect the gut intestinal barrier against the break of tolerance that occurs when gluten is introduced into the diet of genetically at-risk children.

A Newly Characterized Form of Tau May Be Involved in Initiating Alzheimer’s Disease
Featuring Bradley T. Hyman, MD, PhD, and Judith A. Steen, PhD

In studies of the brains of patients with Alzheimer’s disease, researchers found a soluble form of tau that is not present in classic tau aggregates but has the same toxic properties. This suggests that the soluble tau may be an earlier step in the process that ultimately leads to neurodegeneration. More research is needed to understand this form of tau and explore new strategies to block it.

High School Students Who Report Using Alcohol, Cannabis or Nicotine at Higher Risk for Suicidal Thoughts and Other Mental Health Disorders
Featuring Randi M. Schuster, PhD

In a survey-based study of high school students, alcohol, cannabis, and nicotine use were each associated with suicidal thoughts as well as depression/anxiety symptoms, psychotic experiences, and attention deficit hyperactivity disorder symptoms. The strengths of these associations were generally similar regardless of the type of substance used. These associations were evident in a 2022–2023 survey completed by students across Massachusetts as well as a national survey from 2021. Findings suggest that students with frequent substance use are likely to present with other psychiatric symptoms that put them at risk for negative long-term outcomes.

Research Spotlights

Epinephrine Use in the Treatment of Anaphylaxis in Infants and Toddlers
Featuring Michael Pistiner, MD, MMSc and Carlos Camargo, MD, MPH

Michael Pistiner, MD, MMSc, a physician investigator in the Pediatric Allergy Group at Mass General for Children and an assistant professor of pediatrics at Harvard Medical School, is lead author of a recent study in the Journal of Allergy and Clinical Immunology (In Practice), “Factors Associated With Epinephrine Use in the Treatment of Anaphylaxis in Infants and Toddlers”. Carlos Camargo, MD, MPH, DrPH, is senior author of the study.

Screening for Post-Traumatic Stress Disorder Following Childbirth Using the Peritraumatic Distress Inventory
Featuring Sharon Dekel, PhD

Sharon Dekel, PhD, is founding director of the postpartum traumatic stress laboratory and an investigator in the Department of Psychiatry at Massachusetts General Hospital and an assistant professor of Psychology in the Department of Psychiatry at Harvard Medical School, is senior author of a recent study in the Journal of Affective Disorders, “Screening for Post-Traumatic Stress Disorder Following Childbirth Using the Peritraumatic Distress Inventory”.

Establishing the Validity of a Diagnostic Questionnaire for Childbirth-related Post-Traumatic Stress Disorder
Featuring Sharon Dekel, PhD

Sharon Dekel, PhD, is founding director of the postpartum traumatic stress laboratory in the Department of Psychiatry at Massachusetts General Hospital and an assistant professor of psychology in the Department of Psychiatry at Harvard Medical School, is the senior author of a recent study in the American Journal of Obstetrics and Gynecology, “Establishing the Validity of a Diagnostic Questionnaire for Childbirth-related Post-traumatic Stress Disorder”.

The Impact of Synchronizing Phosphenes on Object Binding in Artificial Vision
Featuring John S. Pezaris, PhD

John S. Pezaris, PhD, an investigator in the Department of Neurosurgery at Massachusetts General Hospital and an assistant professor of Neurosurgery at Harvard Medical School, is the senior author of a recently published study in IOVS, “The Influence of Phosphene Synchrony in Driving Object Binding in a Simulation of Artificial Vision”.

Predicting Single Cell Gene Expression from Images Through AI
Featuring Jian Shu, PhD

Jian Shu, PhD, an investigator in the Cutaneous Biology Research Center at Massachusetts General Hospital and an assistant professor of Dermatology at Harvard Medical School as well as an associate member of Broad Institute of MIT and Harvard, is co-senior author of a new paper in Nature Biotechnology, “Prediction of Single-Cell RNA Expression Profiles in Live Cells by Raman Microscopy with Raman2RNA”.

Eplerenone May Reduce Arterial Inflammation Among Individuals with HIV
Featuring Suman Srinivasa, MD, MS

Suman Srinivasa, MD, MS, a physician investigator in the Endocrine Division/Metabolism Unit at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School, is the first author of a new report in JAMA Cardiology, “Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV”. This study was conducted in collaboration with Ahmed Tawakol, MD and Shady Abohashem, MD of the Cardiovascular Imaging Research Center/Division of Cardiology at Massachusetts General Hospital.

Stigma and HCV Cure Cascade Among Individuals Who Inject Drugs
Featuring Abigail Batchelder, PhD, MPH

Abigail Batchelder, PhD, MPH, an investigator in the Department of Psychiatry at Massachusetts General Hospital and an associate professor of Psychology at Harvard Medical School is the lead author of a recently published paper in Drug and Alcohol Dependence, “Shame and Stigma in Association with the HCV Cascade to Cure Among People Who Inject Drugs”.

Optogenetic GABA Neuron Targeting Improves Alzheimer's Pathology
Featuring Ksenia V. Kastanenka, PhD

Ksenia V. Kastanenka, PhD, an investigator in the Department of Neurology and an assistant professor of Neurology at Harvard Medical School, is the senior author of a recently published paper in Molecular Degeneration, “Sleep restoration by optogenetic targeting of GABAergic neurons reprograms microglia and ameliorates pathological phenotypes in an Alzheimer’s disease model”.

Using Self-Supervised Learning to Improve the Analysis of Liver Ultrasound
Featuring Abder-Rahman Ali, PhD

Abder-Rahman Ali, PhD, a research fellow in the Department of Radiology at Massachusetts General Hospital, is the first author of a new study in 37th Conference on Neural Information Processing Systems (NeurIPS 2023) – Self-Supervised Learning: Theory and Practice workshop – “Self-Supervised Learning Meets Liver Ultrasound Imaging”. Anthony Samir, MD, is senior author.

Tofacitinib Is Effective in Treating Refractory Immune Checkpoint Inhibitor Hepatitis
Featuring Michael Dougan, MD, PhD and Ryan Sullivan, MD

Michael Dougan, MD, PhD, a physician investigator in the Division of Gastroenterology at Massachusetts General Hospital and an associate professor of Medicine at Harvard Medical School, and Ryan Sullivan, MD, a physician investigator at the Mass General Cancer Center and an associate professor of Medicine at Harvard Medical School are co-senior authors of a new study in Clinical Gastroenterology and Hepatology, “Tofacitinib Is Effective in Treating Refractory Immune Checkpoint Inhibitor Hepatitis”. Additional Mass General Brigham authors include Kerry Reynolds, MD, Kamaneh Montazeri, MD, Esperance Schaefer, MD, MPH, and Mike Wang, MD.

Transportation Insecurity and Adverse Health Outcomes Among Adults with Chronic Liver Disease
Featuring Nneka Ufere, MD

Nneka Ufere, MD, MSCE, a physician-investigator in the Division of Gastroenterology and Hepatology at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School, is lead author of a new paper in Hepatology Communications, “Health Care-related Transportation Insecurity is Associated with Adverse Health Outcomes Among Adults with Chronic Liver Disease”.

Modeling Study Shows that Policies to Reduce Wealth Inequality Could Improve Health and Life Expectancy of Americans
Featuring Kathryn Himmelstein, MD

Kathryn Himmelstein, MD, a clinical and research fellow in the Division of Infectious Diseases at Massachusetts General Hospital, is lead author of a new study in JAMA Internal Medicine, “Wealth Redistribution to Extend Longevity in the US”.

Blog Posts

Snapshot of Science: Mass General’s High Impact Research Publications for December 2023

PTSD from childbirth, Brain Care Score and much more

Announcing the Finalists for the 2023 MGRI Image Awards

Please join us in congratulating this year’s finalists in five categories, as well as our People’s Choice Award winner.

Benchmarks: Mass General Research News and Notes for January 5, 2024

A genetic link between early risers and anorexia nervosa, bacteria that protect against Celiac disease, the tweets of the week and lots more.

Mass General Investigators Demonstrate that a Single Dose of HPV Vaccine Provides Effective Protection Against Cervical Cancer
Featuring Ruanne Barnabas, MD

In a recent paper published in Nature Medicine, Mass General investigators provide further scientific evidence that one-dose of the HPV vaccine provides effective protection against cervical cancer.

Benchmarks: Mass General Research News and Notes for January 12, 2024

New research into the connections between leisure-time exercise and heart health, pregnancy and stress plus the tweets of the week and more.

Regular Exercise Could Be the Key to Reducing Risk of Alcoholic Liver Disease
Featuring Jay Luther, MD and Jessica Shay, MD, PhD

Alcohol use and alcoholic liver disease is on the rise globally, and researchers at Mass General are looking for new ways to help.

Benchmarks: Mass General Research News and Notes for January 19, 2024

Multivitamins help to protect cognitive health, exploring the connections between obesity and cancer risk, the tweets of the week & more.

Maternal Health Awareness Day: How Mass General Researchers are Working to Help

Today is Maternal Health Awareness Day, and we want to highlight some of our recent stories about maternal health research happening at Mass General.

Benchmarks: Mass General Research News and Notes for January 26, 2024

Explaining how cell therapies work, a new research leader at the Benson-Henry Institute, the tweets of the week, how cults work and more.

And the 2023 MGRI Image Awards Winners Are…

We’re proud to announce the winners of the 2023 MGRI Image Awards. See the winners in each category and learn more about them and their research.

Anderson Draws on Experience to Guide the MGB Research Community Through Challenging Times

Paul Anderson, MD, PhD, Chief Academic Officer of Mass General Brigham, is working to support the system’s research and education missions.

National Mentoring Month 2024

In celebration of National Mentoring Month, we asked research mentees about how their Mass General mentors have shaped their careers.

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Snapshot of Science for January 2024