Validation of the MOG-AR score: a retrospective multicenter study.
Recently, a simple score (the MOG-AR Score), including onset age, sex, onset attack phenotype, use of immunosuppressive therapy, and duration of oral glucocorticoids treatment, has been proposed to identify patients at high relapse risk since onset.11
The aim of this study was to provide the first validation of the MOG-AR Score in a national multicenter cohort and to assess other factors associated with a relapsing disease.
New in JNeurosci from Kosteletou-Kassotaki et al: A white matter tract connecting the inferior colliculus to the basolateral amygdala via the MGB of the thalamus is linked to better hearing ability and higher self-reported fearfulness in people.
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Rapid and efficient fear processing is essential for survival. In vision, this function is supported by a well-characterized subcortical pathway consisting of direct projections from the pulvinar of the thalamus to the amygdala in the human brain. In contrast, the existence of an analogous shortcut for fear in audition has been demonstrated in non-human animals, but remains unconfirmed in humans. To address this question, we used probabilistic streamline tractography and fixel-based analysis on diffusion-weighted images from Human Connectome Project participants of either sex, to reconstruct candidate auditory subcortical pathways and examine their associations with affective and auditory behavioral measures. Our findings revealed a robust white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body (MGB) of the thalamus. Remarkably, higher fiber density in this tract was associated with better hearing ability in noise and increased self-reported fearfulness, supporting its role in auditory and affective function. Conversely, a control analysis of the core thalamocortical pathway from ventral MGB to primary auditory cortex (PAC), representing the main route for auditory processing, was associated with auditory ability but not with affective measures. These findings provide previously unreported evidence for an auditory colliculo-geniculo-amygdala “low road” in humans, aligning with evolutionarily conserved pathways for fear described in non-human species.
Significance Statement Rapid fear processing is crucial for survival. While a visual subcortical “low road” for fear is well characterized in humans, the existence of an analogous human auditory shortcut remains undetermined. Using diffusion magnetic resonance imaging tractography, we provide evidence for a white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body of the thalamus, which is associated with hearing ability and self-reported fearfulness. Our findings provide novel evidence for an auditory colliculo-geniculo-amygdala direct route in humans, revealing an evolutionarily conserved pathway for fear previously described in non-human species.
Among patients with chronic stroke and severe contralesional impairment, targeted ipsilesional arm training supported significant and sustained improvements in ipsilesional motor performance vs best practice therapy.
Importance Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis.
Objective To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits.
Design, Setting, and Participants This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex.
Characterizing molecular aging features is crucial for understanding systemic and local factors contributing to the aging process. Here Costa, Chen et al. performed RNA sequencing on 13 tissues across six ages in male and female African turquoise killifish. This sex-balanced killifish aging atlas provides a comprehensive resource for studying aging dynamics across tissues in the killifish—a powerful, short-lived vertebrate model of aging.
Despite overall improvements, women with STEMI in China still face longer pre-hospital delays than men, especially in rural areas. The gap is driven mostly by delayed EMS calls. Cardiology.
HealthEquity STEMI
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Defined as reduced caloric intake or selective limitation of specific nutrients without malnutrition, is one of the most robust interventions known to extend lifespan and healthspan across species. Studies from yeast to mammals demonstrate that DR elicits conserved genetic, transcriptional, and epigenetic programs that promote cellular maintenance and stress resistance. At the molecular level, DR engages evolutionarily conserved nutrient-sensing pathways, including insulin/IGF-1 signaling (IIS), the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and NAD+-dependent sirtuins, which converge on key transcription factors (TFs) and transcriptional coactivators (TCs) to coordinate metabolic and longevity-associated gene expression. Downstream, these pathways enhance autophagy and proteostasis, remodel mitochondrial function and redox balance, reshape immune and inflammatory networks, and induce epigenetic and transcriptional reprogramming. Recent work further highlights amino acid–specific sensing mechanisms, endocrine mediators such as fibroblast growth factor 21 (FGF21), the gut microbiome, circadian regulators, and nuclear pore–associated transcriptional plasticity as integral components of DR responses. Importantly, the physiological outcomes of DR are context dependent and influenced by genetic background, sex, age at intervention, and the type and duration of restriction. In this review, we summarize current knowledge on the genetic and molecular architecture underlying DR-induced longevity and health benefits across species, discuss implications for aging-related diseases, and outline future directions toward precision nutrition and safe translational strategies.
Aging is characterized by a progressive decline in physiological integrity, reduced stress resilience, and increased susceptibility to chronic diseases (Lopez-Otin et al., 2023). Among numerous genetic, pharmacological, and lifestyle interventions examined over the past decades, dietary restriction (DR) remains the most robust and evolutionarily conserved strategy for extending lifespan and improving healthspan. Originally described in rodents nearly a century ago, the beneficial effects of reduced nutrient intake have since been validated in a wide range of organisms, including yeast, nematodes, flies, and mammals (Wu et al., 2022). While often used interchangeably, it is critical to distinguish between different nutritional interventions to avoid conceptual overlap. Caloric restriction (CR) typically refers to a chronic reduction in total calorie intake (usually 20%–40%) without malnutrition.
Among adults treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss, efficacy was greater in women than men, but similar across age, race, ethnicity, baseline body mass index, and hemoglobin A1c.
These findings indicate that GLP1RA therapy for weight loss is broadly effective across key patient characteristics, supporting inclusive clinical decision-making. GLP-1 RAs include semaglutide, liraglutide, exenatide, lixisenatide, and dulaglutide.
Question How heterogeneous are the treatment effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on weight loss, by age, sex, race and ethnicity, baseline body mass index, and baseline hemoglobin A1c?
Findings In this systematic review and meta-analysis of 41 articles representing 64 randomized clinical trials, the efficacy of GLP-1 RAs was greater among women than men but did not otherwise differ by age, race and ethnicity, baseline body mass index, or baseline hemoglobin A1c.
Meaning Except for the difference by sex, the efficacy of GLP-1 RAs for weight loss appears to be consistent across many important subpopulations of patients who may be eligible for treatment.
About one-third of adolescents and young adults, with or without Cancer, reported at least one social risk such as financial hardship or food insecurity, highlighting the need for routine screening.
This cross-sectional study used data from KPNW, an integrated health care system serving more than 620 000 members in northwest Oregon and southwest Washington, representing approximately 16% of the region’s population. The KPNW Institutional Review Board deemed the study exempt from review and informed consent under category 4 of the Common Rule, meaning that this research was determined to be low risk as it involves the use of secondary data. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies.
Members of KPNW are demographically similar to the surrounding community, with a broad age distribution (approximately 23% aged 18–35 years and 40% aged 36–64 years), a nearly equal sex distribution (52% female), and a racial and ethnic composition comparable to that of the regional population. Approximately 18% of members live below 200% of the federal poverty level, and approximately 80% receive coverage through employer-sponsored plans, contributing to high annual retention rates (approximately 88%). In early 2020, KPNW implemented a social risk screening tool via the EPIC-based (Epic Systems Corp) HealthConnect system. Full details of the screening process have been previously described.22,23
We included KPNW members aged 15 to 40 years who received care at KPNW; completed the social determinants of health screener between January 1, 2022, and December 31, 2024 (the first screening was defined as the index date); and had at least 6 months of follow-up data (eFigure 1 in Supplement 1).
Researchers have identified a new type of blood-based biomarker test for Alzheimer’s disease that measures structural changes in proteins, providing more information on the underlying biology of the disease than standard blood tests. The findings, published in Nature Aging, also provide new insights into how Alzheimer’s disease biology may differ between males and females.
“This work introduces a fundamentally new, blood-based approach to detecting and staging Alzheimer’s disease,” said Dr. Richard Hodes, director of NIH’s National Institute on Aging (NIA). “By revealing protein structural changes associated with genetic risk, symptom severity, and sex differences—features not captured by existing biomarkers—this research could enable earlier diagnosis and more effective clinical trials.”
