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Abstract INTRODUCTION Multicomponent non‐pharmacological interventions, such as the HABIT Healthy Action to Benefit Independence & Thinking® program, have shown promise for improving emotional well‐being, functioning, and self‐efficacy in both people with mild cognitive impairment (pwMCI) and their care partners. However, limited research has examined whether outcomes differ based on type of care partner who co‐enrolls with the pwMCI. METHODS We analyzed data from 875 pwMCI−care partner dyads who completed the HABIT program. Multivariate linear mixed‐effects regression models evaluated changes from baseline in outcomes by care partner type (spouse vs. non‐spouse) at post‐intervention, 6‐months, and 12‐ months. RESULTS At post‐intervention, pwMCI with spousal care partners demonstrated significant improvements across all outcomes from baseline, whereas those with non‐spousal partners improved in five out of seven outcomes. Across subsequent follow‐ups, pwMCI with spousal care partners showed sustained mean reductions in anxiety (post‐intervention: −2.0; 12‐month: −0.9) and increased compliance (post‐intervention: 5.7; 12‐month: 0.9). Everyday functioning in memory (post‐intervention: −0.9; 12‐months: 1.8) and executive functioning (post‐intervention: −0.7; 12‐months: 4.8) improved at post‐intervention but declined thereafter. Spousal care partners reported reduced anxiety (−1.2) and depression (−1.3) at post‐intervention, but by 12‐months they experienced increased burden, anxiety, and depression relative to baseline. Non‐spousal pwMCI–care partner dyads did not show significant change at 6 or 12‐months. DISCUSSION The HABIT intervention may have more favorable outcomes for pwMCI and care partners in spousal compared to non‐spousal dyads. These findings highlight the potential impact of care partner characteristics on both immediate and long‐term response to behavioral interventions for MCI. Highlights At post‐intervention, people with mild cognitive impairment (pwMCI) with spousal care partners showed significant improvements across all outcomes, while those with non‐spousal partners improved in five of seven outcomes. Gains attenuated over time for both spousal and non‐spousal dyads Spousal care partners reported reduced anxiety and depression at post‐intervention, but by 12 months they experienced increased burden, anxiety, and depression relative to baseline. Non‐spousal pwMCI–care partner dyads did not show significant change at 6 or 12 months.

Abstract Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework’s utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.

Background Breast cancer-related lymphedema (BCRL) is a common and life-long adverse event affecting ~20% of breast cancer survivors. As existing non-pharmacologic management is burdensome, expensive, and variably effective, this systematic scoping review aims to identify pharmacologic and herbal agents for prevention and treatment for BCRL. Methods PubMED, Embase, Web of Science Core collection, and the Cumulative Index to Nursing and Allied Health Literature were searched for studies published in English between 1993 and 2025 that investigated the preventative or therapeutic effect of pharmacologic or herbal agents on BCRL among adult stage I-III breast cancer patients. Studies describing interventions with systemically absorbed anti-inflammatories, anti-thrombotics, anti-coagulants, and blood product components were included. Systematic reviews, protocols for ongoing clinical trials, preclinical and non-human studies, editorials, and studies not exclusive to BCRL were excluded. Three reviewers screened and extracted data between June and August 2025. The primary outcomes of interest were reduction in BCRL incidence or severity. Results Of the 217 articles screened, 37 were included in the final review. After full text review, 13 were excluded for repetitive data, non-English language, or irrelevant outcomes. The 24 studies included in the analysis investigated anti-diabetic, herbal, anti-inflammatory, anti-hypertensive, immunomodulatory, and microbiome modifying agents, and venoactive flavinoid derivates. Three studies explored the role of pharmacologic/herbal agents in BCRL prevention. While thiazolidinediones, anti-hypertensives, and non-steroidal anti-inflammatory drugs (NSAIDs) had no effect on BCRL incidence, glucagon-like peptide-1 receptor agonists (GLP-1 RA) were associated with BCRL prevention. In the 21 studies that assessed the effect of pharmacologic/herbal agents in BCRL treatment, NSAIDs/steroids, anti-hypertensives, microbiome/synbiotic supplements, and doxycycline showed no benefit and data for flavonoid-derived venoactive agents and herbal products were inconsistent. Immune-modulating therapies were associated with improved BCRL signs/symptoms in three studies. Conclusion This systematic scoping review found limited evidence suggesting that GLP-1 RAs may reduce the risk of BCRL and that immunomodulatory agents may improve signs/symptoms of BCRL. Rigorous prospective trials using standardized limb volume/edema, quality-of-life (QoL), and symptom measures and longer follow-up are needed to inform clinical practice aimed at preventing and treating BCRL. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251055134.

Objectives: To determine the frequency with which emergency medical services (EMS) clinicians recognize patients enrolled in hospice and describe their prehospital management. Methods: Observational cohort study of patients enrolled in hospice who were transported by EMS within a health system between May 5, 2018, and June 4, 2023. Two physicians reviewed each encounter to determine whether interventions were comfort-focused (hospice philosophy) or life-sustaining care. Interrater reliability was 100% (k = 1.0). Descriptive statistics are provided. Results: EMS clinicians identified hospice enrollment in 51% ( n = 46) of 88 encounters. Most patients (90%, n = 79) received comfort-focused care. Life-sustaining care was provided to four patients identified as hospice-enrolled and included cardiopulmonary resuscitation, an advanced airway, and vasopressors ( n = 1, 25%); spinal immobilization ( n = 2, 50%), and naloxone ( n = 1, 25%). Conclusion: Most patients received care consistent with the philosophy of hospice. However, EMS clinicians may have only identified half of patients enrolled in hospice. This demonstrates an opportunity to improve recognition of patients’ care preferences, starting in the out-of-hospital setting.

PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.