White matter hyperintensities (WMHs) are common in both Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), yet their spatial tissue characteristics and microstructural differences remain poorly understood.

We analyzed 351 participants: 184 amyloid beta (Aβ)-positive AD and mild cognitive impairment (MCI), 139 Aβ-negative cognitively normal controls (CN), and 28 probable CAA. Multimodal magnetic resonance imaging metrics were used to estimate spatial gradient parameters for periventricular WMHs (pWMH) and deep WMHs (dWMH).

CAA demonstrated distinctive free-water fraction (FWF), fractional anisotropy (FA), mean diffusivity (MD), and plasma volume within pWMH, as well as spatial gradient parameters of pWMH. These pWMH spatial gradient parameters produced area under the curve (AUC) values of 0.71 (FWF), 0.72 (MD), and 0.79 (FA) when distinguishing CAA from AD/MCI. We retested a subset of the cohort after 1 to 2 years (AUCs: FWF = 0.89, MD = 0.79, FA = 0.85).

Spatial gradient parameters reflect disease-specific microstructural and vascular changes, providing insights into CAA and AD pathology.

Food allergies (FA) arise from a complex interplay between an individual's genetic predisposition and environmental factors and their prevalence is increasing. Genome-wide association studies (GWAS) to date have been hindered by small sample sizes and varying FA definitions.

Identify novel food allergy risk loci by conducting a GWAS meta-analysis in children and adults using a multi-phenotype approach to ensure the trade-off between sufficient sample size and valid FA definitions.

Analyses were conducted separately in children and adults based on the following FA phenotypes: self-report, doctors-diagnosis, food-specific sensitization, and doctors-diagnosis plus food-specific sensitization. GWAS from up to 16 cohorts of European ancestry including 229,426 adults and 14,234 children were meta-analyzed. Models were adjusted for sex, age, principal components, and if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases.

37 SNPs met suggestive significance (p-value < 1x10^-6), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctors-diagnosed FA plus food-specific sensitization phenotype (stable after additional hay fever adjustment) and rs8022829 (AKAP6-NPAS3) which was significant only in the hay fever-adjusted model in adults. However, neither variant was validated. Further, we identified three SNPs previously reported for FA and atopic diseases.

This study identified 37 SNPs suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on its shared genetic architecture with allergies.

Evidence for gut-kidney interactions in early kidney disease is limited, particularly in community-dwelling adults with largely preserved kidney function. Here, we quantified links between gut microbiota and estimated glomerular filtration rate (eGFR) in two population-based Swedish cohorts.

Deep shotgun metagenomics profiled fecal samples from 9788 adults in the Swedish CArdioPulmonary BioImage Study (SCAPIS) discovery cohort (mean age 58 ± 4 years; 52 % women) and 2080 adults in the Malmö Offspring Study (MOS) replication cohort (mean age 40 ± 14 years; 52 % women). Linear regression related the relative abundance of 494 metagenome-assembled species to the creatinine-based eGFR (by CKD-EPI equation), adjusting for demographics, albuminuria, cardiovascular risk factors and technical variables. Species passing false discovery rate under 0.05 in SCAPIS were tested in MOS for significant concordant direction. Functional enrichment linked eGFR-associated species to gut metabolic modules and plasma metabolites; partial Spearman correlations assessed metabolite/species/eGFR relationships.

The alpha diversity showed a modest inverse association with eGFR across both cohorts. We identified 44 bacterial species consistently associated with eGFR in both cohorts, collectively explaining 7% of its variance. Enrichment analysis highlighted histidine and carnitine metabolism among the top three pathways involved. Their key products, trimethylamine N-oxide and imidazole propionate, were inversely related to eGFR, and a metabolite panel accounted for 51% of eGFR variation, underscoring metabolite-mediated microbial effects. Sensitivity analyses upheld these findings.

Gut microbial diversity and 44 reproducible species are independently linked to kidney function in community dwelling adults. Enrichment of histidine and carnitine pathways, and their circulating metabolites implicates microbial metabolism as a contributor to eGFR variability, suggesting tractable targets for early kidney protection.

Preeclampsia is a pregnancy-related disorder characterized by systemic endothelial dysfunction and angiogenic imbalance, most notably elevated levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF). While preeclampsia has been associated with long-term cardiovascular and cognitive risks, the specific role of angiogenic imbalance in predicting postpartum memory impairment remains unclear. Identifying biomarkers that can anticipate future neurocognitive outcomes may offer opportunities for early intervention and monitoring.

To evaluate whether preeclampsia and angiogenic imbalance during pregnancy, defined by an sFlt-1/PlGF ratio ≥38, are associated with subjective memory impairment 3 to 6 years postpartum.

Cross-sectional study at a tertiary hospital in Barcelona, Spain. Individuals were prospectively recruited during pregnancy and re-evaluated 3 to 6 years postpartum. Preeclampsia was defined per ACOG criteria. Angiogenic imbalance during pregnancy was defined as sFlt-1/PlGF ≥38 (determined between 28 and 40 weeks of gestation). Subjective memory performance was assessed using the validated Memory Failures of Everyday Life (MFE-30) questionnaire. Memory impairment was defined as a total MFE-30 score ≥36. Logistic and linear regression models were used to examine associations, adjusting for relevant confounders.

A total of 266 individuals were re-evaluated between August 2023 and February 2025. 81 of them (30.45%) had a documented history of PE. Participants with an elevated sFlt-1/PlGF ratio during pregnancy showed a higher prevalence of memory impairment (30.0% vs. 16.2%, p = 0.03). In multivariable analysis, angiogenic imbalance remained significantly associated with increased odds of memory impairment (odds ratio = 2.18, 95% CI [1.02-4.65], p = 0.04). In contrast, preeclampsia diagnosis alone was not significantly associated with memory outcomes (odds ratio = 1.35, 95% CI [0.70 to 2.60], p = 0.37).

An elevated sFlt-1/PlGF ratio during pregnancy is associated with increased risk of subjective memory impairment 3 to 6 years postpartum. These findings highlight the potential utility of angiogenic biomarkers as early indicators of long-term cognitive vulnerability, supporting the need for longitudinal follow-up and targeted preventive strategies in women exposed to angiogenic imbalance during pregnancy.

Asciminib represents a significant advancement in the treatment of chronic myeloid leukemia, establishing a novel therapeutic paradigm by specifically targeting the ABL1 myristoyl pocket, a mechanism distinct from that of conventional adenosine triphosphate-competitive inhibitors. Such a selective inhibitor offers an alternative treatment strategy for patients with chronic myeloid leukemia who have developed resistance to previous tyrosine kinase inhibitor therapies. Although asciminib demonstrates a superior safety profile, primarily characterized by a reduction in cardiovascular adverse events associated with prior tyrosine kinase inhibitors, its clinical significance extends further. The effectiveness of asciminib, combined with its capacity to overcome resistance through combination strategies with adenosine triphosphate-binding site tyrosine kinase inhibitors, establishes it as a focal point in emerging chronic myeloid leukemia treatment approaches. It remains essential to continue research and clinical trials to enhance the therapeutic efficacy of asciminib and manage its associated side effects.

Myocardial ischemia-reperfusion injury (MIRI) involves tissue damage following restoration of blood flow. Stearoyl-CoA desaturase 1 (SCD1), associated with metabolic disorders, may contribute to MIRI. This study investigated the mechanism of SCD1 in MIRI. A rat ischemia/reperfusion (I/R) model was established by ligating the left anterior descending coronary artery. The hypoxia/reoxygenation (H/R) model was used to simulate in vitro I/R. 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry were performed for histopathological analysis of rat heart tissues. The ferroptosis indicators were detected using commercial kits and Western blot. Lactylation and ubiquitination of SCD1 were detected by Western blot. I/R increased tissue damage and SCD1 expression. In addition, SCD1 inhibition attenuated ferroptosis in H/R cells and I/R hearts. H/R induced ferroptosis via promoting lactylation modification in H9c2 cells. Mechanistically, lactylation of SCD1 at K208 stabilized its protein stability and activated Wnt/β-Catenin signaling to promote ferroptosis in H9c2 cells. In vivo, SCD1 silencing inhibited the MIRI. SCD1 lactylation drove ferroptosis in MIRI by regulating Wnt/β-Catenin signaling, offering potential therapeutic insights.

As a metabolite of vitamin A, retinoic acid (RA) is bound to nuclear receptors (RAR/RXR) to produce effects and regulate gene expression, showing antioxidant, anti-inflammatory, and anti-apoptotic activities [1]. Oxidative stress, induced by both endogenous and exogenous factors, results in the excessive accumulation of reactive oxygen species (ROS) in specific areas, which can damage cellular components and lead to neurodegenerative diseases, cancer, cardiovascular diseases, and photoaging. RA modulates oxidative stress through various molecular mechanisms, including interaction with the Nuclear factor erythroid 2-related factor 2- Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathway and epigenetic regulation of antioxidant enzymes [2]. Research suggests that RA has considerable benefits in treating a range of diseases, including neurodegenerative diseases, skin aging, obesity, and metabolic syndrome. This review aims to provide an overview of the molecular mechanisms by which RA regulates oxidative stress and evaluate its therapeutic potential in these diseases, offering insights for future applications of RA in the prevention and treatment of these conditions.

Recently expanded WHO guidelines on differentiated service delivery (DSD) include expanded eligibility for adolescents and youth living with HIV (AYLHIV). We evaluated implementation of a stepped care program that included DSD for stable AYLHIV and intensified services, including mental health counseling, for AYLHIV with greater needs.

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to guide evaluation of the Data-informed Stepped Care (DiSC) study, a cluster randomized controlled trial implemented from April 2022 to August 2023 in 24 HIV care facilities in Kenya. We used a mixed methods convergent parallel design to evaluate performance indicators across RE-AIM dimensions. Surveys were analyzed using descriptive statistics and qualitative data using directed content analysis.

Of 3,945 AYLHIV ages 10-24 years old attending care at intervention facilities, 933 AYLHIV were screened and 895 were enrolled, representing an enrollment rate of 96% and 23% reach of the intervention. Distribution by age groups were 10-14 years: 29%; 15-19 years: 48%; 20-24 years: 24%. Perceived effectiveness, including improved retention and viral suppression among AYLHIV, motivated continued implementation throughout the study duration. Providers also identified opportunities to improve AYLHIV outcomes by highlighting the importance of integrating mental health into HIV care programs. Prior to implementation, 49 health providers were trained to deliver the DiSC intervention, representing adoption by 25% of the total facility workforce, including 95% of clinical officers and 56% of nurses. Implementation was facilitated by provider-identified, fidelity-consistent adaptations to optimize contextual fit of the intervention. Key determinants influencing implementation were provider collective efficacy, compatibility with clinic workflows, leadership engagement, and alignment with changing national guidelines. Post-trial, providers supported continued use of the DiSC intervention (maintenance), citing leadership support, training, and material and human resources as key influencers on future sustainment.

Applying RE-AIM to evaluate performance indicators of a stepped care program for AYLHIV identified high adoption and perceived effectiveness, and key influences on implementation and maintenance. Providers were motivated to adopt and sustain use of the DiSC intervention because of perceived positive impact on health system efficiencies and AYLHIV outcomes.

ClinicalTrials.gov, NCT05007717. Registered 13 July 2021.

Achieving high-quality passive data in smartphone-based digital phenotyping studies remains a significant challenge in real-world settings where technical barriers and inconsistent user engagement limit continuous data collection. In response to the field's overreliance on imputation methods and model-based approaches, we present LINC, a framework of best practices that supports the collection of high-quality passive data in digital phenotyping research. LINC, which stands for Launch, Interact, Notify, and Correct, systematizes operational procedures across four domains: (a) device and app configuration, (b) participant engagement with the app, (c) real-time data monitoring, and (d) troubleshooting disruptions in passive data collection. Each component is accompanied by practical resources designed to facilitate implementation without requiring specialized technical expertise. To demonstrate feasibility, we applied the LINC framework to a large observational study (n = 373) examining social media use and youth mental health over a two-to three-week period. Our study, following this systematized approach, achieved a median GPS-based passive data quality of 0.92 (IQR: 0.59-0.98), with 75% of participants surpassing 0.59 and 25% exceeding 0.98. These results compare favorably to published benchmarks and demonstrate that it is feasible to achieve high-quality passive data in digital phenotyping research.

Adolescent sleep is linked to indices of health and well-being, including academic performance, physical health, mood, and safety. However, biological, psychological, and social changes make it difficult for adolescents to obtain enough quality sleep. As a result, the percentage of adolescents who achieve optimal sleep has steadily diminished for decades. Reversing this trajectory requires a multipronged approach and involvement from numerous stakeholders, including adolescents themselves. To support this need, the National Sleep Foundation sponsored a multidisciplinary Adolescent Sleep Health Conference to identify recommendations to improve adolescent sleep health in the United States and beyond.

The 2022 Adolescent Sleep Health Conference convened 22 experts (educators, administrators, parents, advocates, researchers, clinicians, and an adolescent representative) to discuss evidence related to adolescent sleep health and its intersections with health, education, athletics, transportation, and the workforce. Final recommendations reflect those generated during the Conference and additional post hoc recommendations informed by extant literature.

Factors influencing adolescent sleep are present at individual, social, and societal levels. Societal factors such as school start times, entering the workforce, driving, and clock changes are linked to adolescent sleep. Improving adolescent sleep health involves integrating developmental science, family, and educational contexts into sleep health recommendations, implementing healthy school start times and adopting permanent standard time, increasing awareness of the impact on work and driving, and prioritizing sleep health equity.

Policy changes and prioritization across settings can increase the opportunity and likelihood of healthy sleep. Adolescents must be included as contributors to improving sleep health.