tbuckley/cabot-search huggingface dataset:
Development and Validation of a Tool to Predict Onset of Mild Cognitive Impairment and Alzheimer Dementia
Authors: Chenyin Chu, Yifei Wang, Yihan Wang, Christopher Fowler, Georgios Zisis, Colin L. Masters, James D. Doecke, Benjamin Goudey, Liang Jin, Yijun Pan, Michael W. Weiner, Paul Aisen, Ronald Petersen, Laurel Beckett, Richard J. Perrin, Arthur W. Toga, Andrew J. Saykin
Journal: JAMA Network Open (2025)

Importance The ability to predict the onset of mild cognitive impairment (MCI) and Alzheimer dementia (AD) could allow older adults and clinicians to make informed decisions about dementia care. Objective To assess whether the age at onset of MCI and AD can be predicted using a statistical modeling approach. Design, Setting, and Participants This prognostic study used data from 2 aging and dementia cohort studies—the Australian Imaging, Biomarker and Lifestyle (AIBL) study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI)—for model development and validation of the Florey Dementia Index (FDI), a tool used to predict the age at onset of MCI and AD in older adults. Data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study were used for a simulated trial. Data were collected from 1665 AIBL participants, 2029 ADNI participants, and 93 A4 participants from October 1, 2004, to March 1, 2023. The data analysis was conducted between January and August 2024. Main Outcomes and Measures Predicted age at onset compared with clinically observed age at onset. Results Among the 1665 AIBL participants (741 [44.5%] female) and 2029 ADNI participants (925 [45.6%] female), the mean (SD) age at first evaluation was 71.8 (7.1) years and 74.5 (6.7) years, respectively. The FDI achieved mean absolute errors of 2.78 (95% CI, 2.63-2.93) years for predicting MCI onset and 1.48 (95% CI, 1.32-1.65) years for predicting AD onset. In the simulated trial with 93 A4 participants (48 [51.6%] female; mean [SD] age at baseline, 73.4 [5.1] years), the FDI achieved mean absolute errors of 1.57 (95% CI, 1.41-1.71) years for predicting MCI onset and 0.70 (95% CI, 0.53-0.88) years for predicting AD onset. Conclusions and Relevance In this prognostic study, the FDI was developed and validated to predict the onset age of MCI and AD. This tool may be useful in organizing health care for older adults with cognitive decline or dementia and in the future may help prioritize patients for the use of disease-modifying monoclonal antibody drugs.
Interstate Telemedicine in the Courtroom
Authors: Charles G. Kels
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
C-Reactive Protein and Response to Adalimumab in Patients With Hidradenitis Suppurativa
Authors: Simon J. Gunter, Martina L. Porter, Alexa B. Kimball
Journal: JAMA Dermatology (2025)

This post hoc analysis of 2 randomized clinical trials examines whether C-reactive protein estimated response to adalimumab in patients with hidradenitis suppurativa.
Corticosteroids for Sepsis, Acute Respiratory Distress Syndrome, or Community-Acquired Pneumonia
Authors: Peggy B. Leung, Andrew M. Davis, Joshua Davis
Journal: JAMA (2025)

This JAMA Clinical Guidelines Synopsis summarizes the 2024 Society of Critical Care Medicine guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia.
Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials
Authors: Michelle Matvey, D. Parker Kelley, Ellen R. Bradley, Winston Chiong, Aoife O’Donovan, Josh Woolley
Journal: JAMA Psychiatry (2025)

There is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful. When participants can tell whether they received active drug or placebo, their responses to clinical assessments, questionnaires, and even their functional imaging and biological data can be influenced by preconceptions about treatment effects. Positive patient expectancies combined with ineffective masking may skew outcomes and inflate effect sizes. This complicates efforts to determine the safety and efficacy of psychedelic drugs. Here, we explore a method to help address this problem: modifying informed consent to obscure information about the study design. We reviewed all contemporary (2000-2024) clinical trials of psychedelic or methylenedioxymethamphetamine (MDMA) therapy and corresponded with the investigators to compile information on the use of modifications to informed consent in these studies. Modifying informed consent to obscure details of the study design has been implemented in several psychedelic clinical trials and may offer a way to strengthen masking. However, this approach poses significant ethical risks. We examine examples of modifications used in the psychedelic literature, discuss the current regulatory landscape, and suggest strategies to mitigate risks associated with modified informed consent. Incorporating modified informed consent in future psychedelic clinical trials may improve interpretability and impact, but this has not been explicitly tested. Modifications to informed consent may not be appropriate in all cases, and risks to participants should be minimized by implementing appropriate guardrails.
Recurrent Chest Pain in a Young Female Patient With Family History of Cancer
Authors: Ushasi Saraswati, Jaideep Singh Bhalla, Allan L. Klein
Journal: JAMA Cardiology (2025)

A female patient presents with chest pain, and echocardiography reveals moderate circumferential pericardial effusion, leading to a diagnosis of acute pericarditis. Initial cardiac magnetic resonance imaging phase-sensitive inversion recovery sequences in the sagittal section depict late gadolinium enhancement on the pericardium and pericardial thickening. What would you do next?
“I wuz here”: Training the Eye in Poetry and Medicine
Authors: Rafael Campo
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Irritability and Social Media Use in US Adults
Authors: Roy H. Perlis, Ata Uslu, Jonathan Schulman, Faith M. Gunning, Mauricio Santillana, Matthew A. Baum, James N. Druckman, Katherine Ognyanova, David Lazer
Journal: JAMA Network Open (2025)

Importance Efforts to understand the complex association between social media use and mental health have focused on depression, with little investigation of other forms of negative affect, such as irritability and anxiety. Objective To characterize the association between self-reported use of individual social media platforms and irritability among US adults. Design, Setting, and Participants This survey study analyzed data from 2 waves of the COVID States Project, a nonprobability web-based survey conducted between November 2, 2023, and January 8, 2024, and applied multiple linear regression models to estimate associations with irritability. Survey respondents were aged 18 years and older. Exposure Self-reported social media use. Main Outcomes and Measures The primary outcome was score on the Brief Irritability Test (range, 5-30), with higher scores indicating greater irritability. Results Across the 2 survey waves, there were 42 597 unique participants, with mean (SD) age 46.0 (17.0) years; 24 919 (58.5%) identified as women, 17 222 (40.4%) as men, and 456 (1.1%) as nonbinary. In the full sample, 1216 (2.9%) identified as Asian American, 5939 (13.9%) as Black, 5322 (12.5%) as Hispanic, 624 (1.5%) as Native American, 515 (1.2%) as Pacific Islander, 28 354 (66.6%) as White, and 627 (1.5%) as other (ie, selecting the other option prompted the opportunity to provide a free-text self-description). In total, 33 325 (78.2%) of the survey respondents reported daily use of at least 1 social media platform, including 6037 (14.2%) using once a day, 16 678 (39.2%) using multiple times a day, and 10 610 (24.9%) using most of the day. Frequent use of social media was associated with significantly greater irritability in univariate regression models (for more than once a day vs never, 1.43 points [95% CI, 1.22-1.63 points]; for most of the day vs never, 3.37 points [95% CI, 3.15-3.60 points]) and adjusted models (for more than once a day, 0.38 points [95% CI, 0.18-0.58 points]; for most of the day, 1.55 points [95% CI, 1.32-1.78 points]). These associations persisted after incorporating measures of political engagement. Conclusions and Relevance In this survey study of 42 597 US adults, irritability represented another correlate of social media use that merits further characterization, in light of known associations with depression and suicidality.
Uptake of Maternal RSV Vaccination and Infant Nirsevimab Among Infants Born October 2023 to March 2024
Authors: Karen B. Jacobson, Andrew J. Watson, Maqdooda Merchant, Bruce Fireman, Ousseny Zerbo, Nicola P. Klein
Journal: JAMA Network Open (2025)

This cohort study examines uptake of maternal respiratory syncytial virus (RSV) vaccination and infant receipt of nirsevimab during the early period of availability for these medications.
Smooth, Firm, Skin-Colored Papules on the Nasal Dorsum
Authors: Seneca D. Hutson, Mary E. Lohman, Emma F. Johnson
Journal: JAMA Dermatology (2025)

A healthy 19-year-old man with Fitzpatrick skin type V presented with a 2-year history of smooth, firm, skin-colored papules on the nasal dorsum and bilateral alae. What is your diagnosis?
The protein kinase C modulator bryostatin-1 therapeutically targets microglia to attenuate neuroinflammation and promote remyelination
Authors: Payam Gharibani, Efrat Abramson, Shruthi Shanmukha, Matthew D. Smith, Wesley H. Godfrey, Judy J. Lee, Jingwen Hu, Maryna Baydyuk, Marie-France Dorion, Xiaojing Deng, Yu Guo, Andrew J. Calle, Soonmyung A. Hwang, Jeffrey K. Huang, Peter A. Calabresi, Michael D. Kornberg, Paul M. Kim
Journal: Science Translational Medicine (2025)

In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining the balance among demyelination, neurodegeneration, and myelin repair. Phagocytic and regenerative functions of these CNS innate immune cells support remyelination, whereas chronic and maladaptive inflammatory activation promotes lesion expansion and disability, particularly in the progressive forms of MS. No currently approved drugs convincingly target microglia and macrophages within the CNS, contributing to the lack of therapies aimed at promoting remyelination and slowing disease progression for individuals with MS. Here, we found that the protein kinase C (PKC)–modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound with an established human safety profile, shifts the transcriptional programs of microglia and CNS-associated macrophages from a proinflammatory phenotype to a regenerative phenotype in vitro and in vivo. Treatment of microglia with bryo-1 stimulated scavenger pathways, phagocytosis, and secretion of factors that prevented the activation of neuroinflammatory reactive astrocytes while also promoting neuroaxonal health and oligodendrocyte differentiation. In line with these findings, systemic treatment of mice with bryo-1 augmented remyelination after a focal demyelinating injury. Our results demonstrate the potential of bryo-1 and possibly a wider class of PKC modulators as myelin-regenerative and supportive agents in MS and other neurologic diseases.
Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance
Authors: Ana Martins, Fanni Judák, Zoltán Farkas, Petra Szili, Gábor Grézal, Bálint Csörgő, Márton Simon Czikkely, Elvin Maharramov, Lejla Daruka, Réka Spohn, Dávid Balogh, Andreea Daraba, Szilvia Juhász, Máté Vágvölgyi, Attila Hunyadi, Yihui Cao, Zhenquan Sun, Xuechen Li, Balázs Papp, Csaba Pál
Journal: Science Translational Medicine (2025)

Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in Staphylococcus aureus . Cross-resistance was detected between such candidates and antibiotics currently in clinical use, including vancomycin, daptomycin, and the promising antibiotic candidate teixobactin. These patterns were driven by overlapping molecular mechanisms through mutations in regulatory systems. In particular, teixobactin-resistant bacteria displayed clinically relevant multidrug resistance and retained their virulence in an invertebrate infection model, raising concerns. More generally, we demonstrate that putative resistance mutations against candidate antibiotics are already present in natural bacterial populations. Therefore, antibiotic resistance in nature may evolve readily from the selection of preexisting genetic variants. Our work highlights the importance of predicting future evolution of resistance to antibiotic candidates at an early stage of drug development.
High-frequency epidural electrical stimulation reduces spasticity and facilitates walking recovery in patients with spinal cord injury
Authors: Simone Romeni, Elena Losanno, Daniele Emedoli, Luigi Albano, Filippo Agnesi, Carlo Mandelli, Lina Raffaella Barzaghi, Edoardo Pompeo, Cinzia Mura, Federica Alemanno, Andrea Tettamanti, Paola Castellazzi, Chiara Ciucci, Veronica Fossati, Laura Toni, Heike Caravati, Andrea Bandini, Ubaldo Del Carro, Federica Agosta, Massimo Filippi, Sandro Iannaccone, Pietro Mortini, Silvestro Micera
Journal: Science Translational Medicine (2025)

Spinal cord injury (SCI) causes severe motor and sensory deficits, and there are currently no approved treatments for recovery. Nearly 70% of patients with SCI experience pathological muscle cocontraction and spasticity, accompanied by clinical signs such as patellar hyperreflexia and ankle clonus. The integration of epidural electrical stimulation (EES) of the spinal cord with rehabilitation has substantial potential to improve recovery of motor functions; however, abnormal muscle cocontraction and spasticity may limit the benefit of these interventions and hinder the effectiveness of EES in promoting functional movements. High-frequency excitation block introduced in peripheral nerve stimulation could reduce abnormal activity and lead to more physiological activation patterns. Here, we evaluated the application of high-frequency EES (HF-EES) in alleviating undesired muscular cocontraction and spasticity in two patients with motor incomplete SCI implanted with a commercial 32-channel EES paddle commonly used for pain therapy. To design custom HF-EES protocols, we first mapped the muscles targeted by different EES configurations. Our results showed that HF-EES substantially reduced patellar reflex in one participant and eliminated both patellar reflex and ankle clonus in the other participant. By combining HF-EES and low-frequency EES (LF-EES) to enhance functional movements with intensive rehabilitation, we observed notable improvements in lower limb kinematics, muscle strength, and clinical lower limb motor assessments over the trial period. This study suggests that HF-EES could be an important supplementary tool in SCI treatment, emphasizing the importance of personalized rehabilitation approaches and advanced tools to optimize EES treatments and offering hope for individuals with SCI-related motor deficits.
Targeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis in <i>RUNX1</i> -familial platelet disorder
Authors: Mona Mohammadhosseini, Trevor Enright, Adam Duvall, Alex Chitsazan, Hsin-Yun Lin, Aysegul Ors, Brett A. Davis, Olga Nikolova, Erica Bresciani, Jamie Diemer, Kathleen Craft, Ana Catarina Menezes, Matthew Merguerian, Shawn Chong, Katherine R. Calvo, Natalie T. Deuitch, Shira Glushakow-Smith, Kira Gritsman, Lucy A. Godley, Marshall S. Horwitz, Sioban Keel, Lucio H. Castilla, Emek Demir, Hisham Mohammed, Paul Liu, Anupriya Agarwal
Journal: Science Translational Medicine (2025)

Familial platelet disorder (FPD) is associated with germline RUNX1 mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing (n = 10) combined with functional analysis of samples from patients with RUNX1-FPD (n > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways. Bone marrow from patients with RUNX1-FPD contained an elevated cytokine milieu, exerting chronic inflammatory stress on HSPCs. RUNX1-FPD HSPCs were myeloid biased, had increased self-renewal, and were resistant to inflammation-mediated exhaustion. The bone marrow from patients with RUNX1-FPD showed high transcript and protein expression of CD74 at the preleukemic stage compared with that of healthy controls, which remained high upon patient transformation into leukemia. Further, CD74-mediated signaling was exaggerated in RUNX1-FPD HSPCs compared with healthy controls, leading to the activation of mTOR and JAK/STAT pathways with increased cytokine production. Genetic and pharmacological targeting of CD74 with ISO-1 and its downstream targets JAK1/2 and mTOR reversed RUNX1-FPD differentiation defects in vitro and in vivo and reduced inflammation. Our results highlight that inflammation is an early event in RUNX1-FPD pathogenesis, and CD74 signaling is one of the drivers of this inflammation. The repurposing of JAK1/2i (ruxolitinib) and mTORi (sirolimus) and promoting the advancement of CD74 inhibitors in clinical settings as an early intervention strategy would be beneficial to improve the phenotype of patients with RUNX1-FPD and prevent myeloid progression.
Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models
Authors: A. Scott McCall, Sergey Gutor, Hari Tanjore, Ankita Burman, Taylor Sherrill, Micah Chapman, Carla L. Calvi, David Han, Jane Camarata, Raphael P. Hunt, David Nichols, Nicholas E. Banovich, William E. Lawson, Jason J. Gokey, Jonathan A. Kropski, Timothy S. Blackwell
Journal: Science Translational Medicine (2025)

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which repetitive epithelial injury and incomplete alveolar repair result in accumulation of profibrotic intermediate/transitional “aberrant” epithelial cell states. The mechanisms leading to the emergence and persistence of aberrant epithelial populations in the distal lung remain incompletely understood. By interrogating single-cell RNA sequencing (scRNA-seq) data from patients with IPF and a mouse model of repeated lung epithelial injury, we identified persistent activation of hypoxia-inducible factor (HIF) signaling in these aberrant epithelial cells. Using mouse genetic lineage-tracing strategies together with scRNA-seq, we found that these disease-emergent aberrant epithelial cells predominantly arose from airway-derived ( Scgb1a1-CreER –traced) progenitors and exhibited transcriptional programs of Hif2a activation. In mice treated with repetitive intratracheal bleomycin, deletion of Epas1 (Hif2a) but not Hif1a , from airway-derived progenitors, or administration of the small-molecule HIF2 inhibitor PT-2385, using both prevention and rescue approaches, attenuated experimental lung fibrosis, reduced the appearance of aberrant epithelial cells, and promoted alveolar repair. In mouse alveolar organoids, genetic or pharmacologic inhibition of Hif2 promoted alveolar differentiation of airway-derived epithelial progenitors. In addition, treatment of human distal lung organoids with PT-2385 increased colony-forming efficiency, enhanced protein and transcriptional markers of alveolar type 2 epithelial cell maturation, and prevented the emergence of aberrant epithelial cells. Together, these studies showed that HIF2 activation drives the emergence of aberrant epithelial populations after repetitive injury and that targeted HIF2 inhibition may represent an effective therapeutic strategy to promote functional alveolar repair in IPF and other interstitial lung diseases.