tbuckley/cabot-search huggingface dataset:
DELTA: a method for brain-wide measurement of synaptic protein turnover reveals localized plasticity during learning
Authors: Boaz Mohar, Gabriela Michel, Yi-Zhi Wang, Veronica Hernandez, Jonathan B. Grimm, Jin-Yong Park, Ronak Patel, Morgan Clarke, Timothy A. Brown, Cornelius Bergmann, Kamil K. Gebis, Anika P. Wilen, Bian Liu, Richard Johnson, Austin Graves, Tatjana Tchumatchenko, Jeffrey N. Savas, Eugenio F. Fornasiero, Richard L. Huganir, Paul W. Tillberg, Luke D. Lavis, Karel Svoboda, Nelson Spruston
Journal: Nature Neuroscience (2025)

Abstract Synaptic plasticity alters neuronal connections in response to experience, which is thought to underlie learning and memory. However, the loci of learning-related synaptic plasticity, and the degree to which plasticity is localized or distributed, remain largely unknown. Here we describe a new method, DELTA, for mapping brain-wide changes in synaptic protein turnover with single-synapse resolution, based on Janelia Fluor dyes and HaloTag knock-in mice. During associative learning, the turnover of the ionotropic glutamate receptor subunit GluA2, an indicator of synaptic plasticity, was enhanced in several brain regions, most markedly hippocampal area CA1. More broadly distributed increases in the turnover of synaptic proteins were observed in response to environmental enrichment. In CA1, GluA2 stability was regulated in an input-specific manner, with more turnover in layers containing input from CA3 compared to entorhinal cortex. DELTA will facilitate exploration of the molecular and circuit basis of learning and memory and other forms of plasticity at scales ranging from single synapses to the entire brain.
Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations
Authors: Samantha G. Malone, Christal N. Davis, Zachary Piserchia, Michael R. Setzer, Sylvanus Toikumo, Hang Zhou, Emma L. Winterlind, Joel Gelernter, Amy Justice, Lorenzo Leggio, Christopher T. Rentsch, Henry R. Kranzler, Joshua C. Gray
Journal: Nature Human Behaviour (2025)
396P: Patient-derived tumoroid xenograft models for preclinical validation of therapeutics for pleural mesothelioma
Authors: T. Vancsik, C. Rossel Dorca, M. Ronner, F. Schläpfer, L.R. Herrador, R. Werner, S. Arni, M. Mayura, H. Gehart, I. Schmitt-Opitz
Journal: Journal of Thoracic Oncology (2025)
391P: Melatonin as a radioprotective agent: Assessing its efficacy in preventing lung injury induced by radiation therapy
Authors: H.F. Dincbas, E. Demir, K. Yanar, P. Atukeren, S. Ozkan, G. Senturk, M. Ülker, S.A. Ergen, S. Karacam
Journal: Journal of Thoracic Oncology (2025)
Diagnostic delay and less intensive therapy for people with psoriatic arthritis compared with rheumatoid arthritis: a study nested within an English and Welsh audit data set
Authors: Rachel A Charlton, Emer Gates, Laura C Coates, James Galloway, Neil McHugh, Anita McGrogan, Simon Hackett, Melanie Brooke, Charlotte Cavill, William Tillett
Journal: Annals of the Rheumatic Diseases (2025)

This study aimed to compare time to diagnosis among patients with psoriatic arthritis (PsA) with that of patients with rheumatoid arthritis (RA) and compare initial treatment and outcomes. Patients with PsA were identified from the National Early Inflammatory Arthritis Audit between May 2018 and October 31, 2019, and matched to patients with RA (1:1) on age and sex. Patient characteristics and time to diagnosis were compared between PsA and RA groups. Further comparisons were made, restricted to matched pairs of patients with polyarticular PsA, including disease activity, disease impact, and treatment initiation. In total, 2120 patients with PsA were matched to patients with RA, of which 1250 had polyarticular disease. Symptom duration before referral was longer in patients with PsA than that in patients with RA. Patients with PsA had a longer time from general practitioner (GP) presentation to diagnosis (mean, 112 v 89 days; hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .007), including a delay in diagnosis once referrals were received in secondary care (HR, 0.86; 95% CI, 0.80-0.95; P = .002). In patients with polyarticular disease, less disease-modifying antirheumatic drugs (DMARDs) were prescribed at baseline to patients with PsA compared with those to patients with RA (54.0% and 69.0%, respectively; P < .001). Patients with RA had a higher Disease Activity Score in 28 joints at baseline, but by 3 months, the average score was 0.27 (95% CI, 0.13-0.4) higher in patients with PsA. Compared with patients with RA, patients with PsA have a longer duration of symptoms before referral and a longer interval between presentation to the GP and receiving a diagnosis. Most people agreed a treat-to-target strategy but fewer DMARDs were commenced for patients with PsA than those for patients with RA and a lower improvement in disease activity was achieved at 3 months, suggesting undertreatment.
358P: Baseline circulating immunophenotype may predict irAEs onset in NSCLC patients treated with ICIs
Authors: A. Dodi, F. Pecci, G. Mazzaschi, P. Tamarozzi, M. Manini, M. Peroni, S. D’Agnelli, M. Pluchino, M. Verzè, R. Minari, F. Perrone, P. Bordi, A. Leonetti, F. Quaini, M. Tiseo
Journal: Journal of Thoracic Oncology (2025)
361P: Microbiota biomarkers as predictors of immunotherapy response in patients with advanced non-small cell lung cancer
Authors: J. Vicente-Valor, C. Aguado de la Rosa, M. Paz Cabezas, M. Antonanzas Basa, M. Mateos Gonzalez, S. Tesolato, D. Gomez-Garre, M.J. Bernabé, B. Morales, M. Saiz-Pardo, J.R. Jarabo, A.M. Gómez Martınez, P. Iniesta, J.L. Gonzalez-Larriba
Journal: Journal of Thoracic Oncology (2025)
Author Correction: Bioaccumulation of microplastics in decedent human brains
Authors: Alexander J. Nihart, Marcus A. Garcia, Eliane El Hayek, Rui Liu, Marian Olewine, Josiah D. Kingston, Eliseo F. Castillo, Rama R. Gullapalli, Tamara Howard, Barry Bleske, Justin Scott, Jorge Gonzalez-Estrella, Jessica M. Gross, Michael Spilde, Natalie L. Adolphi, Daniel F. Gallego, Heather S. Jarrell, Gabrielle Dvorscak, Maria E. Zuluaga-Ruiz, Andrew B. West, Matthew J. Campen
Journal: Nature Medicine (2025)
Dual‐Mode Radiosensitization of Esophageal Squamous Cell Carcinoma via SOCS6‐Loaded Virus‐Inspired Manganese‐Bismuth Bimetallic Oxide Nanoparticles
Authors: Rui Ma, Zhi Yang, Xia Miao, Jing Hu, Te Zhang, Li‐Tian Ma, Jin‐Yan Lin, Li‐Na Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract Radioresistance poses a significant obstacle to controlling the recurrence of esophageal squamous cell carcinoma (ESCC) during radiotherapy. It is urgent to develop innovative radiosensitization strategies to improve the prognosis of patients with ESCC. Here, a novel dual‐mode radiosensitizer: a virus‐inspired hollow mesoporous manganese‐bismuth bimetallic oxide nanoparticles (vHMMn‐Bi) encapsulating the radiosensitizing plasmids (suppressor of cytokine signaling 6, SOCS6) is developed, designed to significantly amplify ESCC radiotherapy under hypoxic conditions. After intravenous injection, the SOCS6@vHMMn‐Bi nanoparticles can be efficiently delivered to the tumor site and rapidly invade tumor cells by virus‐like surface‐assisted adhesion. Under X‐ray irradiation, the nanoparticles exhibits a unique dual‐mode sensitization effect, encompassing exogenous and endogenous mechanisms, thereby significantly augmenting the ESCC radiotherapeutic effectiveness. First, the Bi 2 O 3 within the shell can enhance the radiosensitivity owing to its robust X‐ray attenuation characteristics. Second, the SOCS6 released from the interior can inhibit both HIF‐1α and JAK2/STAT3 signaling pathways, triggering ROS upregulation and intensifying radiation‐mediated DNA damage inside ESCC cells. Furthermore, the shell employs MnO 2 to catalyze the decomposition of endogenous H 2 O 2 to increase oxygen generation, alleviating hypoxia within the tumor microenvironment. These nanoparticles demonstrates considerable potential as dual‐mode radiosensitizers with no systemic toxicity and low immunogenicity for amplifying radiotherapeutic efficacy in ESCC.
Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer
Authors: Liqun Yu, Keziah Liebenberg, Yichao Shen, Fengshuo Liu, Zhan Xu, Xiaoxin Hao, Ling Wu, Weijie Zhang, Hilda L Chan, Bo Wei, Philip L Lorenzi, Yang Gao, Igor Bado, Luis Becerra-Dominguez, Charlotte Helena Rivas, Sergio Aguirre, Bradley C Pingel, Yi-Hsuan Wu, Yunfeng Ding, Jun Liu, David G Edwards, Livia S Eberlin, Xiang H-F Zhang
Journal: Immunity (2025)
Seasonal average temperature differences and CVD incidence: results from the US-based Nurses’ Health study, Nurses’ Health Study II, and the Health Professional Follow-up study
Authors: Jochem O Klompmaker, Francine Laden, Francesca Dominici, Peter James, Eric Rimm, Charlie Roscoe, Grete Wilt, Antonella Zanobetti, Jaime E Hart
Journal: Environmental Health Perspectives (2025)

Climate change is one of the greatest health threats facing humanity. Multiple studies have documented the impact of short-term temperature exposure on human health. However, long-term temperature exposures are far less studied. We examined whether exposure to higher or lower summer and winter average temperatures compared to long-term average temperatures were associated with cardiovascular disease (CVD) incidence in three US-based cohorts. We followed 276,618 participants from the Nurses' Health Study (NHS, 1991-2018), the NHSII (1994-2017), and the Health Professionals' Follow-Up Study (1991-2015). We used data (1986-2018) from PRISM Spatial Climate Datasets (800 × 800m spatial resolution) to calculate differences between the summer (June-August) and winter (December-February) average temperatures and the previous 5-year summer and winter average temperatures at residential addresses of each participant. CVD incidence was defined as first nonfatal or fatal MI or nonfatal or fatal stroke. Cox proportional hazard models were used to examine associations with between average temperatures and CVD incidence. Hazard ratios (HRs) and 95% confidence intervals (95%CI) were pooled using random effect meta-analysis. We also examined associations in the populations aged <65 and 65+ years. After pooling HRs, we found no association of summer average temperatures higher than the previous 5-year average temperature, with CVD incidence. A winter average temperature lower than the previous 5-year average was associated with CVD incidence (HR = 0.96 per 2.7°C increase, 95%CI: 0.94, 0.98). Among persons aged <65 years, we observed increased CVD risks with higher summer average temperatures (pooled HR = 1.03 per 1.3°C increase, 95%CI: 1.00, 1.07) and lower winter average temperatures (pooled HR = 0.91 per 2.7°C increase, 95%CI: 0.87, 0.94) compared to the previous 5-year average temperature. Exposure to a winter average temperature lower than the previous 5-year average was associated with an increased CVD risk. Exposure to a summer average temperature higher than the previous 5-year average was associated with CVD incidence in the population aged <65 years, but not in the full population. https://doi.org/10.1289/EHP14677.
Kynurenic Acid and Promotion of Activity-Dependent Synapse Elimination in Schizophrenia
Authors: Funda Orhan, Susmita Malwade, Neda Khanlarkhani, Asimenia Gkogka, Angelika Langeder, Oscar Jungholm, Marja Koskuvi, Šárka Lehtonen, Lilly Schwieler, Kent Jardemark, Jari Tiihonen, Jari Koistinaho, Sophie Erhardt, Göran Engberg, Samudyata Samudyata, Carl M. Sellgren
Journal: American Journal of Psychiatry (2025)

Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels in the CNS of individuals with schizophrenia. However, the factors that cause elevated KYNA levels in schizophrenia, and the mechanisms by which KYNA contributes to pathophysiology, remain largely elusive. The authors used patient-derived cellular modeling to test the hypothesis that KYNA can induce microglia-mediated synapse engulfment by reducing neuronal activity. Patient-derived induced pluripotent stem cells were used to generate 2D cultures of neurons and microglia-like cells, as well as forebrain organoids with innately developing microglia, to study how KYNA influences synaptic activity and microglial uptake of synaptic structures. To verify the experimental data in a clinical context, large-scale developmental postmortem brain tissue and genetic datasets were used to study coexpression networks for the KYNA-producing kynurenine aminotransferases (KATs) regarding enrichment for common schizophrenia genetic risk variants and functional annotations. In these patient-derived experimental models, KYNA induced uptake of synaptic structures in microglia, and inhibition of the endogenous KYNA production led to a decrease in the internalization of synapses in microglia. The integrated large-scale transcriptomic and genetic datasets showed that KYNA-producing KATs enriched for genes governing synaptic activity and genetic risk variants for schizophrenia. Together, these results link genetic risk variants for schizophrenia to elevated production of KYNA and excessive and activity-dependent internalization of synaptic material in microglia, while implicating pharmacological inhibition of KATs as a strategy to avoid synapse loss in schizophrenia.
What Do Four Decades of Research Tell Us About the Association Between Childhood Adversity and Psychosis: An Updated and Extended Multi-Level Meta-Analysis
Authors: Lan Zhou, Iris E. C. Sommer, Pengyuan Yang, Lev Sikirin, Jim van Os, Richard P. Bentall, Filippo Varese, Marieke J. H. Begemann
Journal: American Journal of Psychiatry (2025)

Estimating the current association between childhood adversity and the risk of psychosis is crucial for prevention and intervention. We provided an updated synthesis of evidence from the past four decades, expanded the available data by investigating a broad array of adversity subtypes, and explored sex differences and the age of psychosis onset as relevant factors. We searched PubMed, EMBASE, PsycINFO, Web of Science, WANFANG, and CNKI, for case-control, cross-sectional and cohort studies on the association between adversity and psychotic symptoms/illness. Multi-level meta-analysis, prediction intervals calculation, and sensitivity analyses were conducted. The main analysis included 183 study samples (N=349,265), with 119 case-control studies (15,186 cases; 14,879 controls), 51 cross-sectional studies (N=299,659), and 13 cohort studies (N=19,541). Significant associations between adversity and psychosis were observed across all study designs, yielding an overall odds ratio of 2.80 (95% CI=2.18, 3.60). Secondary analyses revealed that exposure to each adversity subtype increased the odds of psychosis, with the highest odds ratio (3.54 [95% CI=3.04, 4.13]) for emotional abuse, and the lowest odds ratio of (1.58 [95% CI=1.48, 1.68]) for parental antipathy. No statistically significant sex differences were observed, although the odds ratio for sexual abuse was higher for women. Onset of psychosis was earlier in adversity-exposed individuals (mean difference=-0.79 years, 95% CI=-1.47 to -0.12). This is the largest meta-analysis to date on the association between childhood adversity and psychosis. The results have broad clinical implications, as they highlight the need for selective prevention of exposure to early adversities and the implementation of trauma-informed therapies in the treatment of psychosis.
An Update on the Use of Neuromodulation Strategies in the Treatment of Schizophrenia
Authors: Nicholas H. Neufeld, Daniel M. Blumberger
Journal: American Journal of Psychiatry (2025)

The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings. While the majority of neuromodulation studies have focused on patients with mood disorders, predominantly depression, there is an unmet need for patients with schizophrenia, who are in dire need of novel therapeutic options. Advances in neuroimaging and approaches for examining individual variability and transdiagnostic symptoms may lead to more effective neuromodulation treatments in this patient population. This overview explores the modern landscape of invasive and noninvasive neuromodulation treatments for patients with schizophrenia. It begins with approaches that involve diffuse stimulation of the cortex and subcortex and then reviews more focal stimulation approaches at the cortical and subcortical levels. The authors also reflect on the relationship between our understanding of the neurobiology of schizophrenia and neuromodulation interventions.
A spatially resolved transcriptome landscape during thyroid cancer progression
Authors: Tian Liao, Yu Zeng, Weibo Xu, Xiao Shi, Cenkai Shen, Yuxin Du, Meng Zhang, Yan Zhang, Ling Li, Peipei Ding, Weiguo Hu, Zhiheng Huang, Man Him Matrix Fung, Qinghai Ji, Yu Wang, Shengli Li, Wenjun Wei
Journal: Cell Reports Medicine (2025)

Tumor microenvironment (TME) remodeling plays a pivotal role in thyroid cancer progression, yet its spatial dynamics remain unclear. In this study, we integrate spatial transcriptomics and single-cell RNA sequencing to map the TME architecture across para-tumor thyroid (PT) tissue, papillary thyroid cancer (PTC), locally advanced PTC (LPTC), and anaplastic thyroid carcinoma (ATC). Our integrative analysis reveals extensive molecular and cellular heterogeneity during thyroid cancer progression, enabling the identification of three distinct thyrocyte meta-clusters, including TG+IYG+ subpopulation in PT, HLA-DRB1+HLA-DRA+ subpopulation in early cancerous stages, and APOE+APOC1+ subpopulation in late-stage progression. We reveal stage-specific tumor leading edge remodeling and establish high-confidence cell-cell interactions, such as COL8A1-ITHB1 in PTC, LAMB2-ITGB4 in LPTC, and SERPINE1-PLAUR in ATC. Notably, both SERPINE1 expression level and SERPINE1+ fibroblast abundance correlate with malignant progression and prognosis. These findings provide a spatially resolved framework of TME remodeling, offering insights for thyroid cancer diagnosis and treatment.
Occupational exposure to disinfectants and risk of incident cardiovascular disease among US nurses: the Nurses' Health Study II
Authors: Yi-Xin Wang, Orianne Dumas, Raphaëlle Varraso, Yang Sun, Janet W. Rich-Edwards, JoAnn E. Manson, Kenneth J. Mukamal, Yu Zhang, Carlos A. Camargo Jr., Carmen Messerlian
Journal: Environmental Health Perspectives (2025)

Exposure to certain chemicals in disinfectants has been associated with vascular dysfunction in toxicological studies, but the association between disinfectant exposure and clinical cardiovascular disease (CVD) remains unclear.
Harnessing artificial intelligence to transform Alzheimer’s disease research
Authors: Sandrine Andrieu, Randall J. Bateman, Erika Bereczki, Niranjan Bose, Anthony J. Brookes, P. Murali Doraiswamy, Miia Kivipelto, Susan Kohlhaas, Lampros Kourtis, Lefkos T. Middleton, Gregory J. Moore, Jeffrey R. Petrella, Neil Postlethwaite, Ricardo Sainz-Fuertes
Journal: Nature Medicine (2025)
Olmesartan Restores <i>LMNA</i> Function in Haploinsufficient Cardiomyocytes
Authors: Eric J. Kort, Nazish Sayed, Chun Liu, Gema Mondéjar-Parreño, Jens Forsberg, Emily Eugster, Sean M. Wu, Joseph C. Wu, Stefan Jovinge
Journal: Circulation (2025)

BACKGROUND: Gene mutations are responsible for a sizeable proportion of cases of heart failure. However, the number of patients with any specific mutation is small. Repositioning of existing US Food and Drug Administration–approved compounds to target specific mutations is a promising approach to efficient identification of new therapies for these patients. METHODS: The National Institutes of Health Library of Integrated Network-Based Cellular Signatures database was interrogated to identify US Food and Drug Administration–approved compounds that demonstrated the ability to reverse the transcriptional effects of LMNA knockdown. Top hits from this screening were validated in vitro with patient-specific induced pluripotent stem cell–derived cardiomyocytes combined with force measurement, gene expression profiling, electrophysiology, and protein expression analysis. RESULTS: Several angiotensin receptor blockers were identified from our in silico screen. Of these, olmesartan significantly elevated the expression of sarcomeric genes and rate and force of contraction and ameliorated arrhythmogenic potential. In addition, olmesartan exhibited the ability to reduce phosphorylation of extracellular signal–regulated kinase 1 in LMNA -mutant induced pluripotent stem cell–derived cardiomyocytes. CONCLUSIONS: In silico screening followed by in vitro validation with induced pluripotent stem cell–derived models can be an efficient approach to identifying repositionable therapies for monogenic cardiomyopathies.