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PubMed2026

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans↗

PubMed2026

Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation.

BACKGROUND: Multiple sclerosis (MS) is a severe neuroinflammatory disease causing substantial long-term disability. Strong epidemiologic evidence links Epstein-Barr virus (EBV) exposure with MS risk, but genetic evidence for immune target prioritization in EBV-related phenotypes remains limited. METHODS: We integrated single-cell cis-eQTL data from 14 immune cell types with GWASs of an EBV-related clinical phenotype and MS using a single-cell Mendelian randomization framework with colocalization analyses. Candidate eGenes were evaluated in independent cohorts. For multi-SNP instruments, we performed heterogeneity, pleiotropy, MR-Egger, weighted median, mode-based, and MR-PRESSO sensitivity analyses. We also conducted phenome-wide association analyses and queried DrugBank to annotate candidate compounds targeting prioritized genes. RESULTS: We prioritized 43 immune-cell-specific candidate eGenes with convergent genetic support, including 6 for the EBV-related phenotype and 37 for MS. SERPINB1 in NK cells was associated with increased risk of the EBV-related phenotype, whereas HLA-G was associated with decreased risk. For MS, APOM and MSH5 showed protective associations, while AHI1 showed cell-type-dependent, bidirectional associations across immune lineages. Colocalization and independent cohort evaluation supported these findings. Among FDR-significant multi-SNP associations, MR-Egger intercept tests did not indicate directional pleiotropy, although a small subset showed heterogeneity or MR-PRESSO signals. Phenome-wide analyses identified no significant adverse phenotypic associations among evaluable genes at the prespecified threshold. DrugBank annotation nominated sodium nitroprusside, fasudil, artenimol, and choline as hypothesis-generating compounds for experimental follow-up. CONCLUSIONS: This study provides a single-cell genetic framework for prioritizing immune-cell-specific candidate targets for EBV-related phenotypes and MS, and nominates genetically supported targets and pharmacologic hypotheses for experimental investigation.

Humans↗

PubMed2026

Barriers to physical activity in patients with systemic lupus erythematosus in the UK.

INTRODUCTION: Physical activity (PA) may play an important role as a non-pharmacological addition to the management of SLE for disease control and reduction of cardiovascular risk factors. Those with SLE have been reported to engage in PA less than the general population. OBJECTIVE: To describe PA patterns and patient-reported barriers to PA for people with SLE in the UK. METHODS: An online survey was conducted of adults aged ≥ 18 years. Participants were recruited from posters in outpatient clinics, newsletters and Lupus UK social media platforms. Survey questions included demographic information, perception of disease activity, the International Physical Activity Questionnaire (IPAQ) and specific leisure time questions. RESULTS: Two hundred sixty-eight patients participated, with a median (IQR) age of 51 (39-59) years and SLE disease duration of 10 (4-20) years were included. SLE-diagnosis was collected by self-report. In those with complete IPAQ data, 178/228 (79.1%) were in a moderate/high activity group. Participants in this group were more likely to be in employment and had lower levels of fatigue and pain. Fatigue was the most reported barrier to PA, irrespective of activity levels. Participants in the low PA group were more likely to have SLE-specific barriers such as higher disease activity and higher pain scores. CONCLUSIONS: Perceptions and preferences in relation to PA differ greatly between individuals with SLE. The most common self-reported barrier to PA was fatigue. Exploration of individual perceptions of PA should form part of consultations, to address perceived barriers. Key Points • Some patients with self-reported SLE can meet WHO physical activity targets, especially those who remain in work. • Fatigue is the most frequently reported barrier to physical activity for patients, irrespective of their activity levels. • People are less likely to engage in PA if they believe it will negatively affect their SLE.

Humans↗

PubMed2026

Social Isolation and Loneliness Among Older Asian Immigrants Through the Lens of Sense of Coherence: Systematic Review of Qualitative Studies.

AIM: To explore the meaning older Asian immigrants attribute to social isolation and loneliness, their management strategies, utilisation of resources and impact on health. DESIGN: Systematic review of qualitative studies. DATA SOURCES: AgeLine, CINAHL, MEDLINE, ProQuest, PsycINFO, Scopus, and Web of Science databases were searched in September 2024. METHODS: Inclusion criteria: participants were Asian immigrants to Western countries aged 65 and over, community-living and experiencing social isolation and loneliness. Antonovsky's Sense of Coherence was used to frame the thematic analysis. RESULTS: Ten papers were included and analysed deductively using elements of the sense of coherence framework: • Comprehensibility: Social isolation and loneliness are viewed as multifaceted, influenced by cultural and environmental dislocation, language barriers, intergenerational conflicts, deteriorating health and mobility, and socioeconomic challenges. • Manageability: included engaging in culture-specific community programs, family and ethnic community support and living within ethnic enclaves mitigated isolation and loneliness. • Meaningfulness: Strong family ties, active community involvement, spirituality, volunteerism, and cultural practices fostered resilience. However, accepting the changing values of their new world, living independently, and carving their own niche provided meaning to their transformed reality. CONCLUSION: Older Asian immigrants experience social isolation and loneliness through a cultural lens, shaped by migration experiences, language barriers, and shifting family dynamics. Cultural roots, family ties, spirituality, community, acceptance, and independence enhance sense of coherence. Recognising the dynamic interplay between cultural identity, resilience, and adaptation is key to understanding their lived experience. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This review informs culturally sensitive interventions, guiding healthcare, community services, and policy to support social participation, mitigate loneliness through ethno-specific activities, and improve the quality of life for aging immigrant populations in Western countries. REPORTING METHOD: The review was undertaken and reported using the PRISMA guidelines. PATIENT OR PUBLIC INVOLVEMENT: None. PROTOCOL REGISTRATION: PROSPERO (CRD42023425752).

Humans↗

PubMed2026

Intramuscular Fat Infiltration and Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intramuscular fat infiltration (IMFI) is considered to be closely associated with knee osteoarthritis (KOA); however, its overall association, muscle-specific involvement, and clinical relevance remain unclear. OBJECTIVE: To quantify the association between IMFI and KOA, identify affected muscle groups, and evaluate prognostic value. METHODS: We searched PubMed, Web of Science, Scopus, and Embase up to December 2025 for observational studies. Two reviewers independently screened, extracted data, and assessed bias (NOS/JBI). Pooled standardized mean differences (SMDs) were calculated using random-effects models, with subgroup and sensitivity analyses. RESULTS: Seventeen studies were included. IMFI was significantly higher in KOA patients than controls (SMD = 0.63, 95% CI 0.41-0.85, I2 = 84.7%). Anatomically, the anterior thigh muscles (rectus femoris, vastus lateralis, vastus medialis) demonstrated a significant pooled effect (SMD = 0.96, 95% CI 0.66-1.25, I2 = 3.2%) and showed the strongest pooled association, whereas posterior, medial, and composite measures did not demonstrate significant associations. At the individual muscle level, a single study reported a notable association for the semimembranosus (SMD = 1.25, 95% CI 0.57-1.93); however, this finding is based on limited evidence and requires confirmation in future studies. Subgroup by imaging modality: CT demonstrated a significant association (SMD = 0.59, 95% CI 0.28-0.90), while MRI and ultrasound did not show significant associations. Elevated IMFI was also associated with reduced muscle strength, higher KOA incidence, structural progression, and increased knee replacement risk. CONCLUSION: A moderate positive association exists between IMFI and KOA, with notable muscle-specific heterogeneity. Anterior thigh muscles show the strongest pooled association, whereas individual muscle findings require further confirmation. These findings suggest that IMFI may represent a promising potential marker warranting further prospective investigation for risk stratification, though causality and its role in modifying disease progression remain to be established.

Humans↗

PubMed2026

Microbial allies in a cotton pest: A descriptive account of associated microbiota dynamics in Dysdercus cingulatus across development.

BACKGROUND: Hemipteran insects harbour several symbiotic partners, mainly bacteria, which play pivotal roles for hosts like dietary provision, support overall physiology, xenobiotic degradation and manipulate/regulate behaviour. Most of these symbionts usually reside and operate from the digestive tracts of the animals. Cotton is one of the major cash crops in India and Dysdercus cingulatus (D. cingulatus) though a secondary pest, is causing significant destruction of cotton bolls, poor lint quality and reduce oil content of seeds. Premature opening of cotton bolls often leads to bacterial and fungal infections, thus resulting in extensive economic loss worldwide. D. cingulatus is a hemimetabolous insect that comprises of developmental stages like egg, nymph (5 instar stages), and adult. The present work explored the ontogeny specific diversity in the associated microbiota and predicted their probable functional inputs in D. cingulatus. RESULTS: The data obtained using 16S rRNA gene sequencing (NovaSeq 6000) revealed presence of members of Proteobacteria (65.83%), Firmicutes (24%), Actinobacteria (10%) phyla throughout the ontogeny of D. cingulatus. Highest alpha diversity of these symbiotic bacteria was recorded in the third instar nymphs in contrast to rest of the developmental stages. Among all the observed genera, Stenotrophomonas, Hungatella and Glutamicibacter were predominant from egg to adult stages. MicFunPred, a tool used for predicting the probable functional inputs of these symbionts, hinted at their probable stage specific contribution in crucial biochemical pathways such as polyketide biosynthesis, ascorbate/aldarate metabolism, pentose phosphate and glyoxylate cycles, steroid hormone and peptidoglycan biosynthesis, and glycolysis/pyruvate metabolism. CONCLUSIONS: The primary investigations on the ontogenetic composition and diversity of associated microbiota, suggest dynamic shifts in D. cingulatus, concurrent with their probable functions/roles in the host development and metabolism. To the best of our knowledge, this is the first report on symbiotic microbiota variation across the developmental stages of D. cingulatus that provides preliminary descriptive observations that may guide future functional and experimental investigations into microbiota-based pest management.

Animals↗

PubMed2026

Repetitive transcranial magnetic stimulation in functional motor disorders: A systematic review of effects and targets.

OBJECTIVE: To evaluate the effectiveness, safety, and potential mechanistic implications of repetitive transcranial magnetic stimulation (rTMS) in adults with functional motor disorders (FMD), focusing on possible phenotype-specific responses and stimulation protocols. METHODS: Seven databases were searched from inception to July 2026. Randomised and non-randomised interventional studies were included. Risk of bias and evidence certainty were assessed using PEDro, RoB 2, JBI tools, and GRADE. Because of substantial clinical and methodological heterogeneity, findings were synthesised qualitatively. RESULTS: Fourteen studies were included. The primary motor cortex was targeted in 11 studies. Functional tremor showed the most consistent evidence with inhibitory stimulation: one small sham-controlled trial found a significant group-by-time effect on tremor severity (p = 0.007), while an uncontrolled prospective series reported 40 % reduction in postural tremor amplitude (p = 0.05). Evidence for functional weakness was conflicting: excitatory M1 stimulation increased objective strength by 25 % versus 10 % with sham (p = 0.004), whereas the largest inhibitory sham-controlled trial found no benefit (p = 0.80). No severe adverse events were reported, but safety reporting was incomplete. GRADE certainty was moderate for tremor and very low for all other outcomes. CONCLUSIONS: Current evidence is insufficient to establish the efficacy of rTMS in FMD or to recommend phenotype-specific protocols. Preliminary findings support further investigation of inhibitory stimulation for functional tremor, whereas evidence for excitatory stimulation in functional weakness remains uncertain. SIGNIFICANCE: The possible interaction between phenotype and stimulation direction is hypothesis-generating. rTMS should currently be considered an experimental, context-sensitive adjunct within multidisciplinary care, pending adequately powered phenotype-stratified sham-controlled trials. Prospero Registration Number: CRD420251250969.

Humans↗

PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals↗

PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

PubMed2026

Prenatal exposure to particulate matter (PM) and autism spectrum disorder (ASD) among children: a systematic review and meta-analysis.

The global surge in Autism Spectrum Disorder (ASD) cases, coupled with evidence linking prenatal Particulate Matter (PM) exposure to developmental disruption, demands a comprehensive review to design targeted health interventions. This systematic review and meta-analysis aim to evaluate the strength and consistency of evidence linking prenatal PM exposure to ASD across studies, quantifying this relation to identify actionable environmental risk thresholds. This study employed PRISMA protocols to systematically extract and evaluate evidence from PubMed, Web of Science, Scopus, and ScienceDirect (2010-2024), and screened 4,013 articles to identify qualified case-control and cohort studies (n=29). Data synthesis employed random-effects modeling, accompanied by comprehensive assessment through I2 statistics, Q-tests, funnel plots, Duval and Tweedie's trim-and-fill analysis, and Egger's regression, to ensure validity. A meta-analysis of 16 case-control studies revealed a 34 % increased risk of ASD associated with prenatal PM exposure (pooled OR=1.34; 95 % CI: 1.13-1.54), despite substantial between-study heterogeneity (I2=94.02 %, p<0.001). Publication bias was not significant (Egger's test p value=0.114). Critical trimester-specific analysis uncovered that third-trimester exposure significantly increased ASD risk (OR=1.17; 95 % CI: 1.01-1.34), while first-trimester (OR=1.02; 95 % CI: 0.92-1.11; I2=49.18 %, p<0.10) and second-trimester exposures (OR=1.13; 95 % CI: 0.88-1.38; I2=92.59 %, p<0.001) showed non-significant associations. This review identified prenatal and early life exposure to PM as a risk factor for ASD, indicating a trimester-specific vulnerability. It highlighted the necessity of focused air quality interventions and targeted guidance to reduce prenatal PM exposure to alleviate ASD risk during the critical-window.

Child↗

PubMed2026

A child and young person focused systematic review of scrotal ultrasound with Mitigants to identify missed torsion.

BACKGROUND: Diagnostic accuracy of ultrasound for adults is stated as excellent. Paediatric and adult acute scrotal diseases are different. Findings in adults may not apply in children. The authors have seen overconfidence and interpretation with adult disease in mind in children with scrotal pain and have seen testicular loss as a result. OBJECTIVES: To interrogate the literature methodologically to report diagnostic accuracy of ultrasound (US) for the acute scrotum specifically in CYP with a follow-up methodology which allows identification of missed torsion. STUDY DESIGN: We performed systematic review and meta-analysis of studies reporting true diagnostic accuracy of ultrasound for testicular torsion (TT). PubMed, MEDLINE, Scopus, and Web of Science databases were searched from platform start until September 2023 using MeSH terms with protocol as detailed on PROSPERO. Multiple author search was undertaken. Two authors extracted data for included studies. Study quality was reported through QUADAS-2 methodology. Surgical findings or 12 months follow up in non-operative cases would be the gold standard to identify late atrophy due to missed torsion. Studies with methodology to identify missed torsion outwith the initial consult were included for meta-analysis. RESULTS: A total of 6790 cases were reported from the 38 papers identified. Studies were often flawed with poor definition of outcomes and short follow-up duration. Meta-analysis of the 10 high-quality studies revealed pooled sensitivity and specificity of 0.93 and 0.99. Doppler US by trained individuals demonstrated excellent diagnostic accuracy. Nonetheless, on extrapolation of the data, especially where flow was preserved, 5.6% of torsions were missed. DISCUSSION/CONCLUSION: Our review confirms a high diagnostic accuracy of US for TT in CYP. However, a 5.6% missed torsion rate was found if flow alone was considered diagnostic. The authors suggest US should be used as an adjunct in ambiguous cases, ensuring that clinically obvious torsion goes to theatre immediately and is not delayed by ultrasound. TRIAL REGISTRATION: PROSPERO: CRD42023412619.

Humans↗

PubMed2026

Advanced/Novel Stenting for Pediatric Dynamic Airway Collapse.

Pediatric dynamic airway collapse is a complex condition that can impact all levels of the pediatric airway. These conditions can pose life threatening risk to pediatric patients and carry lasting impacts. While traditionally, tracheostomy has been used to address all levels of dynamic collapse, recent advances have allowed for more individualized, anatomy-specific stenting and splinting strategies for treatment. This article covers pathophysiology and the latest evidence on strategies to address nasopharyngeal, oropharyngeal, proximal trachea, and tracheobronchial dynamic collapse.

Humans↗

PubMed2025

The impact of the COVID-19 pandemic on osteoporotic fractures: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. METHODS: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. RESULTS: Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p < 0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p = 0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p = 0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p = 0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p = 0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p = 0.17). CONCLUSION: During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.

Humans↗

PubMed2026

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals↗

PubMed2026

Evolution of Precision Oncology, Personalized Medicine, and Molecular Tumor Boards.

With multiple molecular targeted therapies available for patients with cancer that correspond to a specific genetic alteration, the selection of the best treatment is essential to ensure therapeutic efficacy. Molecular tumor boards (MTBs) play a key role in this process to deliver personalized medicine to patients with cancer in a multidisciplinary manner. Historically, personalized medicine has been offered to patients with advanced cancer, but the incorporation of molecular targeted therapies and immunotherapy into the perioperative setting requires clinicians to understand the role of the MTB. Evidence is accumulating to support feasibility and survival benefit in patients treated with matched therapy.

Humans↗

PubMed2026

Electrocardiographic correlates of pacing induced cardiomyopathy and response to cardiac resynchronization therapy.

BACKGROUND: Chronic right ventricular (RV) pacing (RVP) causes pacing-induced cardiomyopathy (PICM) in only a small number of patients. We evaluated ECG correlates of (i) PICM and (ii) response to cardiac resynchronization therapy (CRT) upgrade. METHODS: We conducted a retrospective case-control study by including all CRT upgrades for PICM (LVEF <50%) at our center between 2014 and 2018. Controls were patients with ≥5 ECGs all demonstrating RVP over ≥2 years and all echocardiographic LVEF ≥50%. Root-summed-squared (3D) ECG was obtained from reconstructed vectorcardiographic X-Y-Z leads. Predictors of PICM and CRT response were assessed as area under ROC curve (AUC) for pre-CRT and Δ (post-CRT - pre-CRT) ECG intervals and QRS voltage-time-integrals (VTI). RESULTS: We included 104 patients with CRT upgrade for PICM (age 73.7 ± 10.5 years, female 29.1%, QRS duration 167.8 ± 25.2 ms, LVEF 28.8 ± 8.0%, ΔLVEF 13.8 ± 10.3%) and 178 controls without PICM (age 73.2 ± 14.9 years, female 52.8%, QRS duration 144.0 ± 20.9 ms, LVEF 56.7 ± 5.2%). PICM was best identified by VTIQRS-3D (AUC 0.851; VTIQRS-3D ≥ 80 μVs sensitivity 87.5%, specificity 63.5%), VTIQRS-Y (0.846), and QRS duration (0.775). CRT response (LVEF increase ≥10% at 3-12 months) occurred in 73/104 (70.2%) patients. Lack of CRT response was best predicted by longer pre-CRT QRS duration (AUC 0.640; QRS duration ≥180 ms sensitivity 45.2%, specificity 83.6%), and less ΔVTIQRS-3D (0.609) and ΔVTIQRS-X (0.608). CONCLUSION: In patients with chronic RVP, VTIQRS-3D ≥ 80 μVs can be used as a screening test for echocardiographic confirmation of PICM. RV-paced QRS duration >180 ms, on the other hand, identifies those who may not respond to CRT upgrade.

Humans↗

PubMed2026

Human iPSC-EV-loaded nanofiber stent coatings accelerate vascular repair by enhancing EGFR/HIF-1α signaling and suppressing ROCK1-mediated remodeling.

Arterial disease management is shifting from antiproliferative drug-eluting stents toward approaches that restore endothelial function and modulate smooth muscle cell (SMC) behavior. Stem cell-derived extracellular vesicles (EVs) carry miRNAs that promote endothelial proliferation and migration while restraining aberrant SMC growth and inflammation. Here, human induced pluripotent stem cell (iPSC)-derived EVs were collected by ultracentrifugation and incorporated into 50:50 poly (lactic-co-glycolic acid) (PLGA 503) core-shell nanofibrous membranes, which were fabricated as stent coatings for sustained release to overcome rapid clearance and poor tissue retention. EVs derived from three independent iPSC lines all enhanced tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic and serum-starved conditions and revealed a trend toward reduced platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cell (SMC) migration. The fabricated core-shell nanofibers enabled sustained EV release, maintaining therapeutic efficacy for 28 days. Small RNA sequencing (NGS) analysis demonstrated that EVs from these independent iPSC lines shared miR-148a-3p and members of the miR-92 family, which collectively accounted for more than 75% of the reads within the 25 top-expressed miRNA set. In vitro, iPSC-EVs enhanced HUVEC proliferation and survival signaling by downregulating the negative regulators ERRFI1 and VHL, which are specific targets of miR-148a-3p and the miR-92 family, thereby activating the EGFR and HIF-1α axes and driving downstream ERK1/2 and VEGF expression under hypoxic and serum starvation stress conditions. Concurrently, iPSC-EVs prevented PDGF-BB-induced SMC phenotypic switching by downregulating ROCK1, a target of miR-148a-3p, thereby inhibiting downstream AKT and ERK signaling and preserving contractile markers while suppressing the synthetic phenotype. In vivo, the iPSC-EV-functionalized scaffolds significantly accelerated re-endothelialization and inhibited neointimal hyperplasia, evidenced by the upregulation of angiogenic factors (VEGF, CD31) and the concurrent suppression of pathological remodeling markers (α-SMA, MMPs) and inflammatory cytokines (IL-6, TGF-β1). Therefore, iPSC-EVs enriched with specific miRNAs and delivered via PLGA 503 core-shell nanofibers promote endothelial repair while suppressing SMC overgrowth, providing a promising strategy for vascular healing.

Core-shell nanofibers↗

PubMed2026

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS × RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans↗