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Role of Prefrontal Cortex Circuitry in Maintaining Social Homeostasis

Biological Psychiatry 2025年第10期97卷 953-960页

作者： Lee, SeungHyun Williams, Ziv M. Department of Neurosurgery Massachusetts General Hospital Harvard Medical School Boston Massachusetts United States Harvard-MIT Division of Health Sciences and Technology Boston Massachusetts United States Program in Neuroscience Harvard Medical School Boston Massachusetts United States

Homeostasis is a fundamental concept in biology and ensures the stability of life by maintaining the constancy of physiological processes. Recent years have witnessed a surge in research interest in these physiological processes, with a growing focus on understanding the mechanisms underlying social homeostasis. This shift in focus underscores our increasing understanding of the importance of social interactions and their impact on individual well-being. In this review, we explore the interconnected research across 3 primary categories: understanding the neural mechanisms influencing set points, defining contemporary factors that can disrupt social homeostasis, and identifying the potential contributions of social homeostatic failure in the development of psychiatric diseases. We also delve into the role of the prefrontal cortex and its circuitry in regulating social behavior, decision-making processes, and the manifestation of neuropsychiatric disorders, such as depression and anxiety. Finally, we examine the influence of more recent factors such as growing social media exposure and the COVID-19 pandemic on mental health, highlighting their disruptive effects. We also identify gaps in current literature through the analysis of research trends and propose future research directions to advance our understanding of social homeostasis, with implications for mental health interventions. © 2024 Society of Biological Psychiatry

关键词： COVID Homeostasis Media Neuroscience Prefrontal Social

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A Better Way to Visualize the Cervix: A Low-Cost Cervical Cancer Screening Device for LMIC Settings

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Journal of Medical Devices 2025年第2期19卷 021002页

作者： Barsukova, Anita Dey Jebran, Ahmad Mujtaba Lynch, Naomi Galgali, Amit Moncada, Andrea Sakerka, Lauren Cotner, Cody Davey, Sonya Nimgaonkar, Vivek Ying, Binbin Mendez, Keegan Traverso, Giovanni MIT Department of Mechanical Engineering CambridgeMA02139 United States MIT Leaders for Global Operations CambridgeMA02142 United States Brigham and Women's Hospital BostonMA02115 United States Weill Cornell Medical Center New YorkNY10065 United States Johns Hopkins Hospital BaltimoreMD21287 United States Harvard-MIT Health Sciences and Technology Program CambridgeMA02139 United States

Cervical cancer is a leading cause of cancer-related mortality worldwide, killing over 300,000 women annually. Lack of resources to perform screening and treatment of cervical cancer in low- and middle-income countries (LMICs) as well as the stigma associated with screening has led to high mortality rates in these regions. Specifically, the speculum - a duck bill-shaped device used to open the vaginal canal for visualization of the cervix by a clinician - does not always provide a clear line of sight to the cervix and can cause patient discomfort due to the concentrated stress it exerts on the vaginal canal. To overcome these barriers, we developed a low-cost screening device for use in LMIC settings that enables better visualization of the cervix at low cervical angles and exerts less pressure on the vaginal walls compared to a speculum in finite element (FE) models. © 2025 by ASME.

关键词： Lung cancer

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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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Protein codes promote selective subcellular compartmentalization

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Science (New York, N.Y.) 2025年第6738期387卷 1095-1101页

作者： Kilgore, Henry R. Chinn, Itamar Mikhael, Peter G. mitnikov, Ilan Van Dongen, Catherine Zylberberg, Guy Afeyan, Lena Banani, Salman F. Wilson-Hawken, Susana Lee, Tong Ihn Barzilay, Regina Young, Richard A. Whitehead Institute for Biomedical Research Cambridge MA United States Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology (MIT) Cambridge MA United States Abdul Latif Jameel Clinic for Machine Learning in Health MIT Cambridge MA United States Department of Biology MIT Cambridge MA United States Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA United States Computational and Systems Biology Program MIT Cambridge MA United States

Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. In this study, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. We developed a protein language model, ProtGPS, that predicts with high performance the compartment localization of human proteins excluded from the training set. ProtGPS successfully guided generation of novel protein sequences that selectively assemble in the nucleolus. ProtGPS identified pathological mutations that change this code and lead to altered subcellular localization of proteins. Our results indicate that protein sequences contain not only a folding code but also a previously unrecognized code governing their distribution to diverse subcellular compartments.

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Ena-bile-ing liver cancer growth

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Science (New York, N.Y.) 2025年第6730期387卷 137-138页

作者： Wolfram Goessling Gastroenterology Division Massachusetts General Hospital Boston MA USA. Genetics Division Brigham and Women's Hospital Boston MA USA. Harvard-MIT Division of Health Sciences and Technology Broad Institute of MIT and Harvard Boston MA USA. Harvard Stem Cell Institute Harvard Medical School Boston MA USA.

Bile acids differentially affect immune cell responses to liver cancer.

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Sociodemographic influences on substance use in psychosis in an African cohort

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Schizophrenia Research 2025年 281卷 157-163页

作者： Campbell, Megan L. Odokonyero, Raymond Akena, Dickens Alemayehu, Melkam Atwoli, Lukoye Chibnik, Lori B. Gelaye, Bizu Gichuru, Stella Kariuki, Symon M. Koenen, Karestan C. Kwobah, Edith Kyebuzibwa, Joseph Mwema, Rehema M. Newton, Charles R.J.C. Post, Kristianna Pretorius, Adele Stevenson, Anne Stroud, Rocky E. Teferra, Solomon Zingela, Zukiswa Stein, Dan J. Hook, Kimberly Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) Program Harvard T.H. Chan School of Public Health and the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT United States SAMRC Unit on Risk & Resilience in Mental Disorders Department of Psychiatry Neuroscience Institute University of Cape Town South Africa Department of Psychiatry Faculty of Medicine and Health Sciences Stellenbosch University South Africa Department of Psychiatry School of Medicine College of Health Sciences Makerere University Uganda Department of Psychiatry School of Medicine College of Health Sciences Addis Ababa University Ethiopia Neuroscience Unit KEMRI-Wellcome Trust Research Program Kenya Stanley Center for Psychiatric Research Broad Institute of Harvard and MIT United States Department of Epidemiology Harvard T. H. Chan School of Public Health United States Department of Neurology Massachusetts General Hospital Harvard Medical School United States Department of Psychiatry Massachusetts General Hospital Harvard Medical School United States Department of Social and Behavioral Sciences Harvard T.H. Chan School of Public Health United States Department of Mental Health Moi Teaching and Referral Hospital Eldoret Kenya Department of Psychiatry University of Oxford United Kingdom Executive Dean's Office Faculty of Health Sciences Nelson Mandela University South Africa

Background: Substance use is common among individuals with psychotic disorders, but limited research exists on the variations in substance use across countries in Africa. This study aims to investigate the frequency of alcohol, tobacco, cannabis, and khat consumption in individuals with bipolar disorder (BD) and schizophrenia (SCZ) across four African countries: South Africa, Ethiopia, Kenya, and Uganda. Methods: We utilized data from the Neuropsychiatric Genetics of African Populations-Psychosis project, a large case-control study which will soon have genetic data on over 42,000 participants, half with psychosis. Information on substance use was collected using the Alcohol, Smoking and Substance Involvement Screening Test v3 (ASSIST). The outcome was categorized into never (lifetime usage, no), irregular usage (weekly or monthly) and regular (daily use) based on reported frequency in the past three months. Each substance was modeled individually as an outcome in ordinal regression model adjusting for demographic factors of sex, education and country. Stratified analyses were performed to assess country-specific effects. Results: Individuals with BD had significantly higher odds of alcohol consumption compared to those with SCZ. Males showed higher odds of alcohol, tobacco, and khat consumption compared to females. Significant variations in alcohol, tobacco, and cannabis consumption were observed across different study countries. Education level was significantly associated with khat consumption, with higher education levels associated with lower odds of consumption. Conclusion: Country and sex-specific differences in substance use behaviors exist in a large-scale African case-control study of people with psychosis. The findings here are in line with previous work regarding sex and regional differences, though they differ from studies conducted in US populations in that minimal evidence was found to support a relationship between level of education and frequency of

关键词： African cohort Bipolar disorder Psychosis Schizophrenia Substance use

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Optical Coherence Elastography Measures Mechanical Tension in the Lens and Capsule in situ

SSRN

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SSRN 2025年

作者： Feng, Xu Li, Guo-Yang Jiang, Yuxuan Shortt-Nguyen, Owen Yun, Seok-Hyun Harvard Medical School Wellman Center for Photomedicine Massachusetts General Hospital 50 Blossom St. BostonMA02114 United States Harvard-MIT Division of Health Sciences and Technology CambridgeMA02139 United States

Lens tension is essential for accommodative vision but remains challenging to measure with precision. Here, we present an optical coherence elastography (OCE) technique that quantifies both the tension and elastic modulus of lens tissue and capsule. This method derives mechanical parameters from surface wave dispersion across a critical frequency range of 1-30 kHz. Using isolated lenses from six-month-old pigs, we measured intrinsic anterior capsular tensions of 0-20 kPa and posterior capsular tensions of 40-50 kPa, induced by intra-lenticular pressure at the cortical surface. Young’s modulus (E) was 1.9 MPa for anterior capsules and 1.2 MPa for posterior capsules. Tensions in cortical tissue (E ~10 kPa) were below 1 kPa. Biaxial zonular stretching (~4% strain) increased anterior capsular tension from near zero to 64 kPa. This acousto-optical method holds significant promise for diagnosing and managing accommodative dysfunctions through lens mechanics assessment in clinical settings. © 2025, The Authors. All rights reserved.

关键词： Dispersion (waves)

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SlideCNA: spatial copy number alteration detection from Slide-seq-like spatial transcriptomics data

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Genome Biology 2025年第1期26卷 1-17页

作者： Zhang, Diane Segerstolpe, Åsa Slyper, Michal Waldman, Julia Murray, Evan Strasser, Robert Watter, Jan Cohen, Ofir Ashenberg, Orr Abravanel, Daniel Jané-Valbuena, Judit Mages, Simon Lako, Ana Helvie, Karla Rozenblatt-Rosen, Orit Rodig, Scott Chen, Fei Wagle, Nikhil Regev, Aviv Klughammer, Johanna Broad Institute of MIT and Harvard Cambridge MA United States Massachusetts Institute of Technology Cambridge MA United States Department of Medical Oncology Dana-Farber Cancer Institute Boston MA United States Department of Microbiology Immunology and Genetics Faculty of Health Sciences Ben-Gurion University Beersheba Israel Gene Center and Department of Biochemistry Ludwig-Maximilians-Universität München Munich Germany Department of Pathology Brigham and Women’s Hospital Boston MA United States Klarman Cell Observatory Broad Institute of MIT and Harvard Cambridge MA United States Genentech 1 DNA Way South San Francisco CA United States

Solid tumors are spatially heterogeneous in their genetic, molecular, and cellular composition, but recent spatial profiling studies have mostly charted genetic and RNA variation in tumors separately. To leverage the potential of RNA to identify copy number alterations (CNAs), we develop SlideCNA, a computational tool to extract CNA signals from sparse spatial transcriptomics data with near single cellular resolution. SlideCNA uses expression-aware spatial binning to overcome sparsity limitations while maintaining spatial signal to recover CNA patterns. We test SlideCNA on simulated and real Slide-seq data of (metastatic) breast cancer and demonstrate its potential for spatial subclone detection. © The Author(s) 2025.

关键词： Cancer Clonality Copy number alterations Single-cell RNA-seq Slide-seq Spatial transcriptomics Tumor microenvironment

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Experience influences the refinement of feature selectivity in the mouse primary visual thalamus

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Neuron 2025年第9期113卷 1352-1362.e4页

作者： Sonoda, Takuma Stephany, Céleste-Élise Kelley, Kaleb Kang, Di Wu, Rui Uzgare, Meghna R. Fagiolini, Michela Greenberg, Michael E. Chen, Chinfei Department of Neurology F.M. Kirby Neurobiology Center Boston Children's Hospital Boston 02115 MA United States Department of Neurobiology Harvard Medical School Boston 02115 MA United States Harvard-MIT Health Sciences and Technology Program Harvard Medical School Boston 02115 MA United States

Neurons exhibit selectivity for specific features: a property essential for extracting and encoding relevant information in the environment. This feature selectivity is thought to be modifiable by experience at the level of the cortex. Here, we demonstrate that selective exposure to a feature during development can alter the population representation of that feature in the primary visual thalamus. This thalamic plasticity is not due to changes in corticothalamic inputs and is blocked in mutant mice that exhibit deficits in retinogeniculate refinement, suggesting that plasticity is a direct result of changes in feedforward connectivity. Notably, experience-dependent changes in thalamic feature selectivity also occur in adult animals, although these changes are transient, unlike in juvenile animals, where they are long lasting. These results reveal an unexpected degree of plasticity in the visual thalamus and show that salient environmental features can be encoded in thalamic circuits during a discrete developmental window. © 2025 Elsevier Inc.

关键词： circuit development dLGN experience-dependent plasticity feature selectivity retinogeniculate synaptic plasticity thalamus

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TractCloud-FOV: Deep Learning-based Robust Tractography Parcellation in Diffusion MRI with Incomplete Field of View

arXiv

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arXiv 2025年

作者： Chen, Yuqian Zekelman, Leo Lo, Yui Cetin-Karayumak, Suheyla Xue, Tengfei Rathi, Yogesh Makris, Nikos Zhang, Fan Cai, Weidong O’Donnell, Lauren J. Harvard Medical School Boston United States Brigham and Women’s Hospital Boston United States Harvard University Boston United States The University of Sydney Sydney Australia Massachusetts General Hospital Boston United States University of Electronic Science and Technology of China Chengdu China Harvard-MIT Health Sciences and Technology Cambridge United States

Tractography parcellation classifies streamlines reconstructed from diffusion MRI into anatomically defined fiber tracts for clinical and research applications. However, clinical scans often have incomplete fields of view (FOV) where brain regions are partially imaged, leading to partial or truncated fiber tracts. To address this challenge, we introduce TractCloud-FOV, a deep learning framework that robustly parcellates tractography under conditions of incomplete FOV. We propose a novel training strategy, FOV-Cut Augmentation (FOV-CA), in which we synthetically cut tractograms to simulate a spectrum of real-world inferior FOV cutoff scenarios. This data augmentation approach enriches the training set with realistic truncated streamlines, enabling the model to achieve superior generalization. We evaluate the proposed TractCloud-FOV on both synthetically cut tractography and two real-life datasets with incomplete FOV. TractCloud-FOV significantly outperforms several state-of-the-art methods on all testing datasets in terms of streamline classification accuracy, generalization ability, tract anatomical depiction, and computational efficiency. Overall, TractCloud-FOV achieves efficient and consistent tractography parcellation in diffusion MRI with incomplete FOV. Copyright © 2025, The Authors. All rights reserved.

关键词： Magnetic resonance imaging

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