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PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗

PubMed2026

Novel environmental contaminant 6PPD-quinone promotes malignant phenotypes in colorectal cancer cells and identifies candidate response-associated genes.

6PPD-quinone (6PPDQ), an oxidative transformation product of the widely used tire antioxidant 6PPD, is a ubiquitous environmental contaminant with bioaccumulation potential and widespread human exposure. Recent epidemiological evidence indicates a positive association between urinary 6PPDQ levels and colorectal cancer (CRC) risk; however, its biological effects on CRC-related phenotypes and associated molecular responses remain unclear. We integrated bioinformatics analysis, prognostic modeling, molecular docking and dynamics simulations, and in vitro experiments to investigate cellular and molecular responses to 6PPDQ in CRC models. Predicted 6PPDQ targets were intersected with CRC prognosis-related genes from The Cancer Genome Atlas, followed by functional enrichment and LASSO regression to construct a prognostic risk model, with 1-, 3-, and 5-year AUC values of 0.727, 0.754, and 0.778, respectively. Molecular docking and 100-ns molecular dynamics simulations suggested interactions between 6PPDQ and candidate proteins, including CPT2, SHC2, SRMS, and STK35. Functional assays showed that 6PPDQ exposure altered proliferation, wound-closure capacity, and invasion in Caco-2 and HCT116 cells across the nanomolar concentration range, with non-monotonic and cell-line-dependent responses. In contrast, NCM460 cells showed no increase in EdU incorporation at 10 or 100 nM, whereas reduced proliferation at higher concentrations was accompanied by increased LDH release. 6PPDQ also altered the expression of several prognosis-associated candidate genes. These findings identify cellular phenotypes and candidate molecular responses associated with 6PPDQ exposure under the tested in vitro conditions, but do not establish their causal roles or in vivo relevance. Further mechanistic and in vivo studies are required.

Humans↗

PubMed2026

The association between prenatal PM2.5 constituent exposure and gestational diabetes mellitus: Exploratory analysis of the potential modifying role of thyroid hormones.

The associations of PM2.5 constituents with blood glucose and GDM remain unclear, and the interplay between PM2.5 exposure and thyroid hormone levels in relation to GDM has not been well characterized. This retrospective cohort study included 1314 pregnant women with data collected through multiple methods. A generalized linear model analyzed PM2.5-glucose links, logistic regression assessed pollutant-GDM associations, and stratified analyses explored these relationships at different thyroid hormone levels. In the study population, first-trimester exposure to SO42- and BC correlated positively with FBG, as did PM2.5 and its components in the second trimester. First-trimester SO4²⁻ exposure (OR=1.26, 95% CI: 1.06, 1.51) and second-trimester exposures to PM2.5 (OR=1.67, 95% CI: 1.19, 2.35), NO3⁻ (OR=1.34, 95% CI: 1.06, 1.68), and NH4⁺ (OR=1.33, 95% CI: 1.06, 1.65) were associated with increased GDM risk. Stratified analyses showed that second-trimester BC and OM were positively correlated with FBG in the high-TSH and low-FT4 strata, respectively. In addition, first-trimester exposure to SO42- (high TSH: OR = 1.42, 95% CI: 1.10, 1.84; low FT4: OR = 1.35, 95% CI: 1.05, 1.74) and to PM2.5 (high TSH: OR = 1.93, 95% CI: 1.14, 3.27; low FT4: OR = 1.82, 95% CI: 1.46, 2.25) in the second trimester were associated with higher odds of GDM. These findings show that PM2.5 exposure was associated with glucose dysregulation and GDM in pregnant women differently by trimester and component. Across the separate TSH- and FT4-stratified analyses, women in the high-TSH and low-FT4 strata, respectively, appeared to show greater susceptibility to air pollution-related GDM. These subgroup findings should therefore be interpreted as exploratory and require validation in future studies.

Effect modification↗

PubMed2026

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples ≥ 10 to ≥ 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

PubMed2026

Age-related macular degeneration associated with glucagon-like peptide-1 receptor agonist use: a systematic review.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively. RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low. CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.

Humans↗

PubMed2026

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4⁺ regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogotá, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (∼2.4-fold decrease in median expression; p = 0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p = 0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p = 0.035) and Amerindian ancestry (p = 0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent↗

PubMed2026

Prevalence and Factors Associated with Receiving a Prescription for a Direct Oral Anticoagulant Among Patients with Atrial Fibrillation on Hospice Admission.

Atrial fibrillation (AF) is prevalent in hospice care, but anticoagulation decisions in this population are not well understood. In this cross-sectional study, we described the prevalence and characteristics associated with direct oral anticoagulant (DOAC) prescription on hospice admission. We used electronic health data from adult decedents with AF in a large, for-profit hospice chain in the United States between January 1, 2017 and December 31, 2019. We used multivariable logistic regression with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Among 13,233 decedents, mean (standard deviation [SD]) age was 84.2 (9.9) years, 53.6% were female, 65.1% were White, and 56.1% were referred to hospice from a hospital. Mean (SD) CHA2DS2-VASc score were 3.8 (1.4) for males and 4.8 (1.3) for females, and mean (SD) HAS-BLED score was 2.2 (1.0). Overall, 8% of patients received a DOAC prescription on hospice admission. Characteristics associated with receiving a DOAC prescription included PPS scores of ≥ 20% (compared to scores < 20%), and receiving hospice care at home, nursing home, assisted living facility, or residential care home (compared to inpatient hospice). Further studies about the risks and benefits of DOAC use are needed to optimize decision-making in this population.

DOAC↗

PubMed2026

Association between prenatal exposure to tetrachloroethylene and adverse birth outcomes: Systematic review and meta-analysis.

BACKGROUND: Tetrachloroethylene (PCE) is a ubiquitous chlorinated solvent with documented placental transfer. Despite widespread environmental and occupational exposure, no prior systematic review has synthesized evidence on prenatal PCE exposure and adverse birth outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, PsycINFO, EMBASE, and CINAHL were searched from inception to July 13, 2026. Eligible studies reported associations between prenatal PCE exposure (drinking water or inhalation) and adverse birth outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) criteria. Random-effects meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs), with Knapp-Hartung adjustments and Paule-Mandel τ2 estimation. RESULTS: Twenty one studies (1987-2023) met inclusion criteria. Prenatal PCE exposure was associated with spontaneous abortion (8 studies; RR = 1.28, 95% CI 1.00-1.63; I2 = 64.2%). Analyses of stillbirth, central nervous system defects, oral clefts, neural tube defects, preterm birth, low birthweight, and small-for-gestational-age (SGA) yielded positive but statistically non-significant pooled estimates. The certainty of evidence ranged from very low to low across outcomes (GRADE). CONCLUSIONS: Prenatal PCE exposure may be associated with spontaneous abortion, particularly at higher exposure levels, and with SGA. Findings support ongoing regulatory efforts to limit PCE in occupational and environmental settings, particularly for pregnant individuals. Future prospective studies with biological monitoring and confounder-adjusted designs are needed.

Tetrachloroethylene↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

Contrasting redox-related physiological responses associated with HaGATA23 and HaGATA36 during Orobanche cumana parasitism in sunflower (Helianthus annuus L.).

Helianthus annuus is an economically important Asteraceae species used for seed oil production and ornamental purposes, but its production is seriously affected by the root-parasitic plant Orobanche cumana. GATA transcription factors are zinc-finger DNA-binding regulators involved in plant development and stress adaptation. However, the molecular characteristics of GATA transcription factors in Helianthus annuus and their contribution to Helianthus annuus -Orobanche cumana interaction remain poorly understood. Here, 36 HaGATA members were retrieved from the Helianthus annuus genome and classified into four phylogenetic clades. Chromosomal placement, collinearity, gene structure, motif composition, and promoter elements varied among the 36 HaGATA members, indicating evolutionary conservation coupled with functional diversification. Expression analysis and RT-qPCR analyses revealed differential expression patterns among HaGATA genes under O. cumana stress, with HaGATA23 markedly downregulated and HaGATA36 strongly upregulated. Overexpression of HaGATA23 was associated with increased malondialdehyde (MDA) accumulation and unfavorable changes in antioxidant enzyme activities, whereas its silencing showed the opposite physiological tendency. In contrast, overexpression of HaGATA36 reduced malondialdehyde accumulation, increased peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, while its silencing showed the reverse tendency. These results indicate that HaGATA23 and HaGATA36 are candidate genes associated with contrasting redox-related physiological responses during O. cumana stress. This work provides evidence that GATA transcription factors are associated with redox-related physiological responses in sunflower under O. cumana treatment and identifies HaGATA23 and HaGATA36 as functionally divergent candidate genes for further validation.

Helianthus↗

PubMed2026

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2026

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC↗

PubMed2026

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans↗

PubMed2026

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (≥15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans↗

PubMed2026

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines↗

PubMed2026

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72 h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR = 5.12; 95% CI: 2.57-12.24; p < 0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity < 0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p = 0.045) and significantly improved risk reclassification (cNRI = 0.4778, p < 0.001; IDI = 0.0240, p = 0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗

PubMed2026

Blood pressure management after endovascular thrombectomy in acute ischemic stroke: association with symptomatic intracranial hemorrhage and functional outcome at 3 months.

BACKGROUND: No clear consensus exists on ideal systolic blood pressure (SBP) targets after endovascular thrombectomy (EVT) following an acute ischemic stroke (AIS). This study investigated the association between SBP parameters within the first 24 h after EVT and 3-month functional outcomes and the risk of symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively collected and prospectively followed clinical, and radiological data for patients undergoing EVT for AIS from 2016 to 2024, including 2-hourly BP measurements during the first 24 h and SBP variability assessed by standard deviation (SD) and coefficient of variation (CV). Outcomes included 3-month functional status and sICH, and their associations with post-EVT BP metrics were analyzed. RESULTS: A total of 268 post EVT patients were included with a median age of 61 years (IQR, 51-69). Mean SBP was 129.67 ± 17.17 mm Hg, with SBP variability (SD 12.6 ± 5.4 mm Hg; CV 9.6 ± 3.8 %), while good functional outcome and sICH occurred in 39.7 % and 4.9 % of patients, respectively. Multivariate regression showed that higher admission NIHSS (>15) [0.90 (95 %CI, [0.86, 0.95], p = 0.000)], recanalization status [1.88 (95 %CI, [1.43, 2.48], p = 0.00)], and SBP-CV ≥ 10 [0.44 (95 %CI, [0.2, 0.94], p = 0.036)] was independently associated with poor 3-month functional outcome, while higher admission NIHSS (>15) [0.87 (95 %CI, [0.77,0.98], p = 0.02)] and diabetes [0.12 (95 %CI, [0.03, 0.54], p = 0.006)] predicted increased risk of sICH. CONCLUSIONS: The study showed that reduced BP variability during the first 24 h post-EVT was associated with better 3-month functional outcomes. A clear association between SBP and sICH risk was not demonstrated.

Humans↗