tbuckley/cabot-search huggingface dataset:
Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer’s disease
Authors: Sebastian N. Roemer-Cassiano, Fabian Wagner, Lisa Evangelista, Boris-Stephan Rauchmann, Amir Dehsarvi, Anna Steward, Anna Dewenter, Davina Biel, Zeyu Zhu, Julia Pescoller, Mattes Gross, Robert Perneczky, Maura Malpetti, Michael Ewers, Michael Schöll, Martin Dichgans, Günter U. Höglinger, Matthias Brendel, Sarah Jäkel, Nicolai Franzmeier
Journal: Science Translational Medicine (2025)

In Alzheimer’s disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner. Here, we hypothesized that neuronal hyperactivity and hypersynchronicity, resulting in functional connectivity increases, constitute a crucial mechanism by which Aβ facilitates the spreading of tau pathology. By combining Aβ positron emission tomography (PET), resting-state functional magnetic resonance imaging, and longitudinal tau-PET in 69 cognitively normal amyloid-negative controls and 140 amyloid-positive patients covering the AD spectrum, we confirmed that Aβ induces hyperconnectivity of temporal lobe tau epicenters to posterior brain regions that are vulnerable to tau accumulation in AD. This was replicated in an independent sample of 55 controls and 345 individuals with preclinical AD and low cortical tau-PET uptake, suggesting that the emergence of Aβ-related hyperconnectivity precedes neocortical tau spreading . Last, using longitudinal tau-PET and mediation analysis, we confirmed that these Aβ-related connectivity increases in tau epicenters to typical tau-vulnerable brain regions in AD mediated the effect of Aβ on faster tau accumulation, unveiling increased connectivity as a potential causal link between the two AD hallmark pathologies. Together, these findings suggest that Aβ promotes tau spreading by eliciting neuronal hyperconnectivity and that targeting Aβ-related neuronal hyperconnectivity may attenuate tau spreading in AD.
APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology
Authors: Kristine M. Tran, Nellie E. Kwang, Claire A. Butler, Angela Gomez-Arboledas, Shimako Kawauchi, Cassandra Mar, Donna Chao, Rocio A. Barahona, Celia Da Cunha, Kate I. Tsourmas, Zechuan Shi, Shuling Wang, Sherilyn Collins, Amber Walker, Kai-Xuan Shi, Joshua A. Alcantara, Jonathan Neumann, Duc M. Duong, Nicholas T. Seyfried, Andrea J. Tenner, Frank M. LaFerla, Lindsay A. Hohsfield, Vivek Swarup, Grant R. MacGregor, Kim N. Green
Journal: Molecular Neurodegeneration (2025)
An MDR Salmonella Enteritidis sublineage associated with gastroenteritis outbreaks and invasive disease in China
Authors: Xiaoyi Zheng, Ying Xiang, Xiaoying Li, Xinying Du, Yule Wang, Sai Tian, Jingzhuang Xue, Ying Huang, Hongbo Liu, Qi Wang, Hongbo Liu, Hui Wang, Chao Wang, Mingjuan Yang, Huiqun Jia, Ligui Wang, Xuebin Xu, Lihua Song, Hongbin Song, Shaofu Qiu
Journal: Journal of Infection (2025)

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a commonly reported pathogen which adapts to multiple hosts and causes critical disease burden at a global level. Here, we investigated a recently derived epidemic sublineage with multidrug resistance (MDR), which have caused extended time-period and cross-regional gastroenteritis outbreaks and even invasive nontyphoidal Salmonella disease (iNTS) in China. Whole-genome sequencing and antimicrobial resistance (AMR) testing were applied to 729 Chinese S. Enteritidis isolates in relation to gastroenteritis outbreaks, gastrointestinal-sporadic and iNTS infections, spanning 28 years (1994-2021) in China. Phylogenomic analysis was performed to explore the population structure and evolutionary history of the Chinese isolates within a global context. Molecular investigations of AMR genes, virulence factors, mobile genetic elements and pan-genomes were also performed. The Chinese S. Enteritidis collections exhibited a high level of multidrug resistance (MDR), including high resistance to nalidixic acid (97.67%). Notably, the multidrug resistance rate of iNTS strains has significantly increased over the past decade. Phylogenomic analysis showed that the majority of the Chinese isolates (98.63%) were distributed in the global pandemic lineage L1, while the other lineages were highly continent-specific. Particularly, the Chinese isolates were predominantly distributed in sublineages L1.2 (37.45%) and L1.3 (59.26%), forming two main Chinese clades (MCC1&2). The most recent common ancestor of MCC1&2 dated back to 1944 and 2004, respectively. The lineage L1, especially MCC1&2, harbored the most amount of AMR determinants and virulence genes, which was mainly due to the presence of a hybrid virulence-resistance plasmid and coexistence of different types of AMR plasmids in S. Enteritidis. S. Enteritidis has evolved unique clonal clusters, MCC1&2, with critical MDR in China, which phylogenetically constitute an extension of the globally epidemic lineage and were characterized by distinct genetic traits. These clades have induced extensive outbreaks of gastroenteritis and serious cases of iNTS in China, underscoring the pressing nature and severity of this public health crisis. Implementing the One-Health strategy, longstanding routine surveillance and further genomic epidemiological studies are urgently required to capture epidemics, monitor changes in bacterial populations and determine the consequent risk to global public health.
Committee on Scientific Sessions Program
Journal: Circulation (2013)

The American Heart Association is grateful to members of the Committee on Scientific Sessions Program for their dedication and leadership throughout the year in planning the program. Robert A. Harrington, MD, FACC, FAHA Chair Ken Bloch, MD, FAHA Vice-Chair Representatives: Ben Abella, MD, MPhil, FACEP, FAHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Nancy T. Artinian, PhD, RN, FAHA, FPCNA, FAAN Cardiovascular and Stroke Nursing Kenneth Baker, MD, FAHA High Blood Pressure Research Harold L. Dauerman, MD Clinical Cardiology Lisa de las Fuentes, MD, MS, FASE Member-at-Large Marcelo F. Di Carli, MD Member-at-Large Gerald W Dorn, II, MD, FAHA Basic Cardiovascular Sciences Alan T. Hirsch, MD Peripheral Vascular Disease Mikhail Kosiborod, MD Quality Care and Outcomes Research Angel Leon, MD, FACC Member-at-Large Donald M. Lloyd-Jones, MD, ScM, FACC, FAHA Epidemiology and Prevention Sanjay Misra, MD Cardiovascular Radiology and Intervention Christopher Newton-Cheh, MD, MPH Functional Genomics and Translational Biology Ravi Nistala, MD Kidney in Cardiovascular Disease Paul Poirier, MD, PhD, FRCPC, FACC, FAHA Lifestyle and Cardiometabolic Health Wolfgang A. Radtke, MD, FAHA Cardiovascular Disease in the Young Marc Ruel, MD, MPH, FRCSC, FAHA Cardiovascular Surgery and Anesthesia Jorge Saucedo, MD, FACC, MBA Member-at-Large Gregory S. Shelness, PhD, FAHA Arteriosclerosis, Thrombosis and Vascular Biology Cathy A. Sila, MD Stroke Kevin Sneed, PharmD Member-at-Large American Heart Association Mariell Jessup, MD, FAHA, President Elliott M. Antman, MD, FAHA, President-elect Rose Marie Robertson, MD, FAHA, Chief Science Officer
Comparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations
Authors: Elysa W. Pierro, Matthew A. Cottam, Hanbing An, Brian D. Lehmann, Jennifer A. Pietenpol, Kathryn E. Wellen, Liza Makowski, Jeffrey C. Rathmell, Barbara Fingleton, Alyssa H. Hasty
Journal: Cancer Research (2025)

Abstract Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies. Here, we utilized lean, obese, and weight loss mouse models to examine the impacts of TREM2 deficiency (Trem2+/+ and Trem2-/-) on postmenopausal breast cancer depending on weight history conditions. Trem2 deficiency constrained tumor growth in lean, but not obese or weight loss, mice. Single-cell RNA sequencing, in conjunction with VDJ sequencing of tumor and tumor-adjacent mammary adipose tissue (mATTum-adj) immune cells, revealed differences in the immune landscapes across the different models. Tumors of lean Trem2-/- mice exhibited a shift in clonal CD8+ T cells from an exhausted to an effector memory state, accompanied increased clonality of CD4+ Th1 cells, that was not observed in any other diet-genotype group. Notably, identical T cell clonotypes were identified in the tumor and mATTum-adj of the same mouse. Finally, anti-PD-1 therapy restricted tumor growth in lean and weight loss, but not obese, mice. These findings indicate that weight history could impact the efficacy of TREM2 inhibition in postmenopausal breast cancer. The reported immunological interactions between tumors and the surrounding adipose tissue highlight significant differences under obese and weight loss conditions.
An Atypical Presentation of Cytokine Release Syndrome With Signs of Arthritis During Treatment With Teplizumab in a Pediatric Patient
Authors: Courtney J. Duckworth, Raymond J. Kreienkamp, Evan C. Rieger, Thinh H. Nguyen, Jason L. Gaglia, Belinda S. Lennerz
Journal: Diabetes Care (2025)
Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia
Authors: Vicente Chapaprieta, Alba Maiques-Diaz, Ferran Nadeu, Guillem Clot, Ramon Massoni-Badosa, Pablo Mozas, Judith Mateos-Jaimez, Anna Vidal Crespo, Stella Charalampopoulou, Martí Duran-Ferrer, Romina Royo, Núria Russiñol, Laura Llaó Cid, Juan A. Piñeyroa, Neus Villamor, Holger Heyn, Sophie A. Herbst, Junyan Lu, Dean J. Bryant, Jonathan C. C. Strefford, Sascha Dietrich, Thorsten Zenz, Julio Delgado, Armando López-Guillermo, Elías Campo, Jose Ignacio Martin-Subero
Journal: Blood (2025)
Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma
Authors: Yakinthi Chrisochoidou, Andrea Scarpino, Salomon Morales, Shannon Martin, Sarah Anne Bird, Yigen Li, Brian A Walker, John Caldwell, Yann-Vai Le Bihan, Charlotte Pawlyn
Journal: Blood (2025)

Immunomodulatory drug (IMiD) resistance is a key clinical challenge in myeloma treatment. Previous data suggests almost one third of myeloma patients acquire mutations in the key IMiD effector cereblon by the time they are pomalidomide refractory. Some events, including stop codons/frameshift mutations and copy loss, having clearly explicable effects on cereblon function. Missense mutations have also been reported throughout the length of cereblon but their functional impact has not been systematically studied. This study modelled selected missense mutations and examined their effect on cereblon function also analysing whether any mutations deleterious to IMiD action could be overcome using the novel cereblon binding agents (CELMoDs). Three patterns of response to missense mutations were apparent, mutations that led to complete loss of CRBN function for all agents, those that had no effect on CRBN function and those with agent-dependent effect on CRBN function. The latter group of 4 mutations were profiled in more detail with confirmatory experiments demonstrating an ability of the more potent CELMoDs to lead to neosubstrate degradation and cell death even though IMiDs were not active. Dynamic modelling based on a newly generated crystal structure of the DDB1/CRBN/lenalidomide complex, with greater resolution than those published to date, helped to understand the impact of these mutations. These results have important implications for the interpretation of CRBN sequencing results from patients for future therapy decisions, particularly differentiating those who may, despite relapsing on IMiDs with CRBN mutations, have the potential to still benefit from the use of CELMoD agents.
GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.
Authors: Fatemeh Alikarami, Hongbo M Xie, Simone S Riedel, Haley Goodrow, Declan Raymond Barrett, Leila Mahdavi, Alexandra Lenard, Changya Chen, Taylor Yamauchi, Etienne Danis, Zhendong Cao, Vu Le-Huy Tran, Mabel Minji Jung, Yapeng Li, Hua Huang, Junwei Shi, Kai Tan, David Trent Teachey, Emery H Bresnick, Tobias Neff, Kathrin Maria Bernt
Journal: Blood (2025)

Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance. We find substantial intra- and inter-patient variability in GATA2 expression across AML patient samples. GATA2 expression varies by molecular subtype and has been linked to outcome. In a murine model, KMT2A-MLL3 driven AML originating from a stem cell or immature progenitor cell population have higher Gata2 expression and are more resistant to the standard AML chemotherapy agent doxorubicin. Deletion of Gata2 resulted in more robust induction of p53 following exposure to doxorubicin. ChIP-Seq, RNA-Seq and functional studies revealed that GATA2 regulates the expression of RASSF4, a modulator of the p53 inhibitor MDM2. GATA2 and RASSF4 are anti-correlated in human cell lines and AML patient cell bulk and single cell expression datasets. Knockdown of Rassf4 in Gata2 low cells resulted in doxorubicin or nutlin-3 resistance. Conversely, overexpression of Rassf4 results in sensitization of cells expressing high levels of Gata2. Finally, doxorubicin and nutlin-3 are synergistic in Gata2-high murine AML, as well as AML patient samples. We discovered a previously unappreciated role for GATA2 in dampening p53-mediated apoptosis via transcriptional regulation of RASSF4, a modulator of MDM2. This role for GATA2 directly links the expression of a stemness associated transcription factor to chemotherapy resistance.
Bright Light Therapy for Nonseasonal Depressive Disorders—Reply
Authors: Artur Menegaz de Almeida, Francisco Cezar Aquino Moraes, Francinny Alves Kelly
Journal: JAMA Psychiatry (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
External Validation of the Walter Index for Posthospitalization Mortality Prediction in Older Adults
Authors: Thiago J. Avelino-Silva, Sei J. Lee, Kenneth E. Covinsky, Louise C. Walter, W. James Deardorff, John Boscardin, Flavia Campora, Claudia Szlejf, Claudia K. Suemoto, Alexander K. Smith
Journal: JAMA Network Open (2025)

Importance The Walter Index is a widely used prognostic tool for assessing 12-month mortality risk among hospitalized older adults. Developed in the US in 2001, its accuracy in contemporary non-US contexts is unclear. Objective To evaluate the external validity of the Walter Index in predicting posthospitalization mortality risk in Brazilian older adult inpatients. Design, Setting, and Participants This prognostic study used data from a cohort of adults aged 70 years or older admitted to the geriatric unit of a university hospital in Brazil from January 1, 2009, to February 28, 2020. Participants underwent comprehensive geriatric assessments at admission, were reevaluated at discharge, and were subsequently followed up for 48 months. Data were analyzed from March to July 2024. Main Outcomes and Measures The Walter Index, a score based on 6 risk factors (male sex, dependent activities of daily living at discharge, heart failure, cancer, high creatinine level, and low albumin level), was calculated to assess its predictive accuracy for 12-month mortality as well as 6-, 24-, and 48-month mortality. The study investigated whether incorporating delirium, frailty, or C-reactive protein level enhanced accuracy. Performance was assessed using discrimination, calibration, and clinical utility measures. Results In total, 2780 participants (mean [SD] age, 81 [7] years; 1795 [65%] female) were included, with 89 (3%) lost to follow-up. The 12-month posthospitalization mortality rate was 23% (646 participants). Mortality was 7% (47 of 634) in the lowest-risk group (0-1 point), 17% (111 of 668) for 2 to 3 points, 25% (198 of 803) for 4 to 6 points, and 43% (290 of 675) in the highest-risk group (≥7 points). The index demonstrated an area under the receiver operating characteristic curve (AUC) of 0.714 (95% CI, 0.691-0.736) for predicting 12-month posthospitalization mortality (AUCs were 0.75 and 0.80 in the original derivation and validation cohorts, respectively). Comparable results were observed for mortality at 6 months (AUC, 0.726; 95% CI, 0.700-0.752), 24 months (AUC, 0.711; 95% CI, 0.691-0.730), and 48 months (AUC, 0.719; 95% CI, 0.700-0.738). Adding delirium modestly increased the index’s discrimination (AUC, 0.723; 95% CI, 0.702-0.749); additionally including frailty and C-reactive protein level did not improve discrimination further (AUC, 0.723; 95% CI, 0.701-0.744). Conclusions and Relevance In this prognostic study of hospitalized older adults in Brazil, the Walter Index showed similar discrimination in predicting postdischarge mortality as it did 2 decades ago in the US. These findings highlight the need for continuous validation and potential modification of established prognostic tools to improve their applicability across settings.
Comments on Consensus for Generalized Pustular Psoriasis—Reply
Authors: Siew Eng Choon, Peter van de Kerkhof, Hervé Bachelez
Journal: JAMA Dermatology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Disseminated Pseudovesicles in an Immunocompromised Patient
Authors: William J. Nahm, Michelle C. Juarez, Daniel R. Mazori
Journal: JAMA Dermatology (2025)

A 41-year-old immunocompromised man presented to the intensive care unit with neutropenic fevers, and after a 1-week stay, developed oral ulcers and tender, diffuse, erythematous pseudovesicular papules, many umbilicated, on the face, trunk, and extremities. What is your diagnosis?
Use and Spending on Medical Equipment Among US Cancer Survivors
Authors: Faraz I. Jafri, Vishal R. Patel, Syed M. Qasim Hussaini, Naveen Premnath, Helen M. Parsons, Anne H. Blaes, Arjun Gupta
Journal: JAMA Network Open (2025)

This survey study assesses patterns of use and costs of medical equipment among US cancer survivors.
Age, Sex, and Anatomical Location Patterns in Cutaneous Pyogenic Granuloma Cases
Authors: Umber Dube, Meagan Corliss, Kevin M. Bowling, Jonathan W. Heusel, Carrie C. Coughlin
Journal: JAMA Dermatology (2025)

Cutaneous pyogenic granulomas (PGs) are commonly encountered, benign, vascular tumors, in which epidemiologic factors have been variably reported, in part, due to sample size limitations and a focus on either adult or pediatric patients. To assemble a large dataset of pathologically diagnosed PGs across the continuum of age and investigate patterns of PGs by demographic factors, including age, sex, and anatomical location. This retrospective case series included case reports of patients with pathologically confirmed PGs of cutaneous origin reported between April 1, 2010, to March 31, 2020. The pathology database at a large tertiary academic center in the Midwestern US was queried for case reports that included the term pyogenic granuloma or lobular capillary hemangioma. Individuals were included in the analytic sample if they had a pathologically confirmed diagnosis of a PG. PG cases were excluded if they included PG only as a part of the pathological differential diagnoses; were recurrent; or were of noncutaneous origin. These data were analyzed between March 2022 and March 2023. The main outcomes were sex biases in frequency overall, by anatomical region, and by left-right laterality using exact binomial tests. Additional outcomes included differences in age-by-sex distribution overall and by anatomical region using Kolmogorov-Smirnov tests. Of 1009 unique pathologically confirmed PG records from 987 individuals, 376 individuals (38.1%) were younger than 18 years, of whom 122 (32.4%) were female. A total of 611 individuals were 18 years and older, of whom 364 (59.6%) were female. Overall, PGs between male and female individuals were equally distributed for all anatomical locations except lower extremities, in which females were more frequently affected. The distribution of PGs by age was significantly different between male and female individuals, with this difference primarily associated with the head/neck and trunk but not with upper extremity or lower extremity anatomical locations. Neither left-right laterality bias among upper extremity PGs nor anterior-posterior bias among truncal PGs was observed. In this retrospective case series, an age-by-sex interaction was found in the incidence of PGs, with PGs on the head/neck and trunk being more common in males younger than 20 years and in females 20 to 50 years of age. These findings suggest that trauma may not be a major etiologic factor for PGs. Future studies are necessary to confirm this and to understand the causes of the age-by-sex interaction.