Nevin Manimala

Int J Gynaecol Obstet. 2026 Jan 12. doi: 10.1002/ijgo.70721. Online ahead of print.

ABSTRACT

OBJECTIVE: The randomized trial of azithromycin to reduce maternal and neonatal sepsis (the A-PLUS Trial) found substantial reduction in maternal sepsis among women receiving azithromycin and substantial non-study antibiotic use. This secondary analysis explored the effect modification of non-study antibiotics on azithromycin versus placebo on maternal and newborn infection among A-PLUS participants.

METHODS: Women ≥28 weeks gestation in labor and planning a vaginal delivery at a study hospital in seven low- and middle-income countries (Bangladesh, India [two sites], Pakistan, Guatemala, Kenya, Democratic Republic of Congo, and Zambia) were eligible for inclusion. Non-study antibiotic use was collected prospectively. We estimated the interaction of non-study antibiotics with azithromycin versus placebo on maternal and newborn sepsis.

RESULTS: A total of 29 287 participants were randomized (14 590 to azithromycin; 14 688 to placebo). Maternal infection was reduced among the azithromycin group compared to placebo among those who did not receive non-study antibiotics, with estimated relative risk (RR) 0.58 (95% confidence interval [CI] 0.48, 0.70), and among those who received non-study antibiotics, with RR 0.80 (95% CI 0.70, 0.91). Similar results were observed for maternal sepsis. Neonatal infection was not significantly reduced in any group. These results were similar when stratified by African and Asian region but not statistically significant.

CONCLUSION: Our results suggest a benefit of azithromycin in reducing maternal infection or sepsis across all groups, with a larger reduction in risk among participants who had not received other antibiotics. Given the concerns of inappropriate use of antibiotics, further research is warranted to determine the most effective strategies of reducing risk of infection.

PMID:41524099 | DOI:10.1002/ijgo.70721

Rev Cardiovasc Med. 2025 Dec 19;26(12):39373. doi: 10.31083/RCM39373. eCollection 2025 Dec.

ABSTRACT

BACKGROUND: Mitral commissural prolapse or flail, characterized by intricate and diverse anatomical features, poses a significant challenge in mitral transcatheter edge-to-edge repair (M-TEER). Previous studies have largely focused on central mitral regurgitation with favorable valve anatomy or a general broad spectrum of complex mitral regurgitation. However, no established approach is currently available for M-TEER in commissural degenerative mitral regurgitation (DMR).

METHODS: Therefore, this study aimed to evaluate the efficacy and safety of a novel morphology classification-guided M-TEER strategy for treating commissural DMR using the MitraClip system. This prospective, multicenter, single-arm, objective performance criteria study involved 12 experienced centers in Asia, primarily located in China. Patients with symptomatic moderate-to-severe (3+) and severe (4+) native DMR and commissural involvement were stratified into three morphological categories based on an echocardiographic core laboratory analysis, and tailored M-TEER strategies were proposed. The primary endpoint is the proportion of patients achieving a mitral regurgitation (MR) grade of ≤1+ without repeat mitral intervention at one-year follow-up. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed over one year.

RESULTS: Based on statistical power calculations, a total of 148 patients are required to achieve adequate power to test the primary efficacy hypothesis, accounting for an estimated 10% attrition rate at 12 months.

CONCLUSIONS: The morphology classification system enhances M-TEER for commissural DMR by addressing the unique challenges of this approach, enabling tailored interventions that optimize procedural success and patient outcomes.

CLINICAL TRIAL REGISTRATION: ChiCTR2400090258, https://www.chictr.org.cn/showproj.html?proj=239191.

PMID:41524053 | PMC:PMC12781021 | DOI:10.31083/RCM39373

NAR Genom Bioinform. 2026 Jan 10;8(1):lqaf206. doi: 10.1093/nargab/lqaf206. eCollection 2026 Mar.

ABSTRACT

Omics Notebook Interactive (OmNI) is an R-based, open-source, and modular framework engineered for streamlined multi-omics data integration and analysis across diverse data types, incorporating interactive visualizations at each processing step. OmNI performs differential expression analysis utilizing customizable linear models, accommodating various covariates and complex experimental designs. For cross-omic layer integration, OmNI employs a modified S-score statistic, ensuring sensitive detection of differential features. The framework also integrates network and metabolomics data, offering detailed insights into regulatory mechanisms through comprehensive enrichment analysis using multiple pathway databases. Outputs include interactive HTML reports, CSV/TSV files, and Cytoscape-compatible objects. OmNI is readily deployable in both local and high-performance computing environments, enabling scalable data processing. Acknowledging the public health concerns of opioids, we performed TMT18-based deep proteome and phosphoproteome analysis of brains from genetically diverse collaborative cross diversity outbred (CC/DO) founder mouse strains exposed to fentanyl to demonstrate OmNI’s capabilities. The integrative S-score uniquely identified differential signaling and interaction hubs conserved across all strains and revealed strain-specific molecular neuro-responses to fentanyl. OmNI is freely available for download at https://github.com/gracerhpotter/OmNI and is also accessible via a web interface at https://emili-laboratory.shinyapps.io/omni/.

PMID:41524030 | PMC:PMC12789801 | DOI:10.1093/nargab/lqaf206

Int J Ophthalmol. 2026 Jan 18;19(1):63-68. doi: 10.18240/ijo.2026.01.08. eCollection 2026.

ABSTRACT

AIM: To evaluate long-term visual field (VF) prediction using K-means clustering in patients with primary open angle glaucoma (POAG).

METHODS: Patients who underwent 24-2 VF tests ≥10 were included in this study. Using 52 total deviation values (TDVs) from the first 10 VF tests of the training dataset, VF points were clustered into several regions using the hierarchical ordered partitioning and collapsing hybrid (HOPACH) and K-means clustering. Based on the clustering results, a linear regression analysis was applied to each clustered region of the testing dataset to predict the TDVs of the 10^th VF test. Three to nine VF tests were used to predict the 10^th VF test, and the prediction errors (root mean square error, RMSE) of each clustering method and pointwise linear regression (PLR) were compared.

RESULTS: The training group consisted of 228 patients (mean age, 54.20±14.38y; 123 males and 105 females), and the testing group included 81 patients (mean age, 54.88±15.22y; 43 males and 38 females). All subjects were diagnosed with POAG. Fifty-two VF points were clustered into 11 and nine regions using HOPACH and K-means clustering, respectively. K-means clustering had a lower prediction error than PLR when n=1:3 and 1:4 (both P≤0.003). The prediction errors of K-means clustering were lower than those of HOPACH in all sections (n=1:4 to 1:9; all P≤0.011), except for n=1:3 (P=0.680). PLR outperformed K-means clustering only when n=1:8 and 1:9 (both P≤0.020).

CONCLUSION: K-means clustering can predict long-term VF test results more accurately in patients with POAG with limited VF data.

PMID:41524021 | PMC:PMC12782057 | DOI:10.18240/ijo.2026.01.08

Int J Ophthalmol. 2026 Jan 18;19(1):140-148. doi: 10.18240/ijo.2026.01.18. eCollection 2026.

ABSTRACT

AIM: To explore the causal relationship between several possible behavioral factors and high myopia (HM) using multivariable Mendelian randomization (MVMR) approach and to find the mediators among them with mediation analysis.

METHODS: The causal effects of several behavioral factors, including screen time, education time, time spent outdoors, and physical activity, on the risk of HM using univariable Mendelian randomization (MR) and MVMR analyses were first assessed. Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.

RESULTS: MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM. Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM. Additionally, MR analyses identified 13 serum metabolites significantly associated with HM, of which 12 were lipids and one was an amino acid derivative. Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM, with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC (p-16:0; 30.83%).

CONCLUSION: This study suggests that in addition to outdoor time, moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity. These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.

PMID:41524010 | PMC:PMC12782062 | DOI:10.18240/ijo.2026.01.18

Int J Ophthalmol. 2026 Jan 18;19(1):90-96. doi: 10.18240/ijo.2026.01.12. eCollection 2026.

ABSTRACT

AIM: To evaluate the efficacy of the total computer vision syndrome questionnaire (CVS-Q) score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.

METHODS: A total of 141 healthy computer users underwent comprehensive clinical visual function assessments, including evaluations of refractive errors, accommodation (amplitude of accommodation, positive relative accommodation, negative relative accommodation, accommodative accuracy, and accommodative facility), and vergence (phoria, positive and negative fusional vergence, near point of convergence, and vergence facility). Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.

RESULTS: The cohort included 54 males (38.3%) with a mean age of 23.9±0.58y and 87 age-matched females (61.7%) with a mean age of 23.9±0.53y. The multiple regression model was statistically significant [R²=0.60, F=13.28, degrees of freedom (DF=17 122, P<0.001]. This indicates that 60% of the variance in total CVS-Q scores (reflecting reported symptoms) could be explained by four clinical measurements: amplitude of accommodation, positive relative accommodation, exophoria at distance and near, and positive fusional vergence at near.

CONCLUSION: The total CVS-Q score is a valid and reliable tool for predicting the presence of various non-strabismic binocular vision anomalies and refractive errors in symptomatic computer users.

PMID:41524008 | PMC:PMC12782083 | DOI:10.18240/ijo.2026.01.12

Int J Ophthalmol. 2026 Jan 18;19(1):132-139. doi: 10.18240/ijo.2026.01.17. eCollection 2026.

ABSTRACT

AIM: To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey (NHANES) database combined with Mendelian randomization (MR).

METHODS: Initially, 20 497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included. By exclusion criteria, 8460 subjects were screened with 1676 myopia samples and 6784 control samples. Subsequently, baseline characteristics, association analyses, risk stratification analyses, and receive operating characteristic curve (ROC) were used to investigate the associations between covariates and myopia. Then, the causal relationship was explored in depth by MR analysis, and was estimated the reliability by sensitivity analyses and directionality tests.

RESULTS: Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates (excluding gender; P<0.05). The results in all three models indicated that asthma was strongly associated with myopia and the effect on myopia was not significantly confounded by other covariates [model 3: odd ratio (OR)=1.31; 95%CI=1.07-1.62; P=0.0133]. The risk stratification analysis again verified that asthma remained strongly associated with myopia and was a risk factor for myopia (P<0.05, OR>1). ROC proved that the model was accurate in its prediction [area under curve (AUC)=0.7]. Subsequently, the causal relationship between them was statistically significant (P<0.05) according to the inverse variance weighted (IVW) method in MR. Scatterplot showed that asthma and myopia had significant positive causality and were not affected by confounders. Forest plot displayed an increasing risk of myopia on asthma (OR>1). The funnel plot demonstrated compliance with Mendel’s second law. Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.

CONCLUSION: A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis, which is important implications for public health policy development and clinical practice.

PMID:41524007 | PMC:PMC12782071 | DOI:10.18240/ijo.2026.01.17

Int J Ophthalmol. 2026 Jan 18;19(1):77-82. doi: 10.18240/ijo.2026.01.10. eCollection 2026.

ABSTRACT

AIM: To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion (CRVO) with macular edema (ME).

METHODS: Optical coherence tomography angiology (OCTA) parameters, including optic disc vessel density (VD; including whole-disc VD, intra-disc VD, and peripapillary VD), superficial/deep capillary plexus (SCP/DCP) VD, and central macular thickness (CMT) were analyzed. Additional assessments included best-corrected visual acuity (BCVA) via Early Treatment Diabetic Retinopathy Study (ETDRS) chart and hemorheological profiling. CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months. Pre- and post-treatment parameters were statistically compared.

RESULTS: The study comprised 60 CRVO-ME patients (28 males; 32 females), aged 50-78y (mean 63.3±7.6y) and 60 age-/sex-matched healthy controls. As compared with participants exhibiting normal funduscopic findings, CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity (LSR-WBV), high-shear-rate whole blood viscosity (HSR-WBV), and aggregation index (AI, all P<0.05). In CRVO-affected eyes, vertical cup-to-disc (C/D) ratio and optic cup volume were significantly smaller, whereas retinal nerve fiber layer (RNFL) thickness was significantly greater, compared to both unaffected contralateral eyes and normal control eyes (all P<0.05). Following treatment, VD of the entire optic disc (P<0.05), intra-disc VD (P<0.05), and peripapillary VD (P<0.05) all increased significantly relative to baseline. CMT decreased significantly (P<0.05), whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions (P>0.05). At baseline, BCVA of CRVO eyes correlated with whole-disc VD (r=-0.276, P=0.033), intra-disc VD (r=-0.342, P=0.009), and peripapillary VD (r=-0.335, P=0.007), with intra-disc VD demonstrating the strongest association. Besides, BCVA improvement, after the treatment, correlated positively with whole-disc VD (r=0.342, P=0.008) and intra-disc VD (r=0.396, P=0.002).

CONCLUSION: Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion, suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO. Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula. CRVO patients shows higher hemorheological parameters than those with normal fundi. Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence, potentially acting as susceptibility factors.

PMID:41524002 | PMC:PMC12782078 | DOI:10.18240/ijo.2026.01.10

Alpha Psychiatry. 2025 Dec 22;26(6):49341. doi: 10.31083/AP49341. eCollection 2025 Dec.

ABSTRACT

OBJECTIVE: This study compared addiction severity, psychotic symptoms, suicide risk, and craving in patients with heroin use disorder, with and without methamphetamine use. We also investigated the reasons for methamphetamine use in these patients, and assessed 3-month clinical follow-up and treatment compliance.

METHODS: This cross-sectional study included 166 inpatients diagnosed with heroin use disorder (DSM-5). Patients were divided into two groups: heroin use only (H), and heroin use + methamphetamine use (H+M). Clinical assessments included the Addiction Profile Index-Clinical Form (API-C), Brief Psychiatric Rating Scale (BPRS), and Suicide Probability Scale (SPS). Statistical analyses were conducted with Statistical Package for the Social Sciences (SPSS) and included descriptive statistics, Kolmogorov-Smirnov test, Chi-square test, Mann-Whitney U test, and logistic regression. Three-month follow-up results and treatment compliance were compared between the two groups.

RESULTS: The H and H+M groups included 80 and 86 participants, respectively. The H+M group had higher BPRS total scores, API-C subscale scores (craving, risky behaviors, excitement-seeking, impulsiveness, depression), addiction severity, additional substance use, anxiety, depressive symptoms, suicidal ideation, and 3-month lapse rate. Craving and excitement-seeking were independent predictors of methamphetamine use.

CONCLUSION: The H+M group showed more severe addiction, novelty-seeking personal characteristics, and suicidal ideation compared to the H group. Craving scores were higher in the H+M group and should not be overlooked, along with a greater risk of early lapse. Our study found that craving, risky behaviors, depressive and psychotic symptoms, and suicidal thoughts are the most critical issues to be addressed in the treatment and follow-up of the H+M patient group.

PMID:41523975 | PMC:PMC12781224 | DOI:10.31083/AP49341

Alpha Psychiatry. 2025 Dec 22;26(6):49352. doi: 10.31083/AP49352. eCollection 2025 Dec.

ABSTRACT

OBJECTIVE: To explore the molecular mechanisms underlying clozapine-induced metabolic syndrome (MetS) in schizophrenia patients, providing scientific evidence for clinicians to prevent and manage metabolic syndrome during the treatment of psychiatric disorders.

METHODS: Ten schizophrenia patients with MetS and ten matched controls were recruited from Shanghai Mental Health Center according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for schizophrenia and the 2016 Chinese Adult Dyslipidemia Prevention and Treatment Guidelines for MetS. Peripheral blood RNA sequencing was performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to pinpoint hub genes. Mendelian randomization (MR) was conducted to validate causal relationship between serum brain-derived neurotrophic factor (BDNF) levels and MetS components.

RESULTS: A total of 1019 DEGs were identified, grouped into eight mRNA modules through WGCNA. Key hub genes included RP11-611O2.6, acid phosphatase-like 2 (ACPL2), T cell receptor alpha variable 12-2 (TRAV12-2), matrix metallopeptidase 8 (MMP8), piggyBac transposable element derived 4 pseudogene 1 (PGBD4P1), transmembrane protein 261 (TMEM261), and BDNF, with BDNF and MMP8 further validated by PPI network analysis. MR analysis confirmed a causal association between BDNF levels and MetS risk, reinforcing its role in metabolic dysregulation. Gene Ontology (GO) annotation and pathway enrichment analysis highlighted immune response, morphological changes, and metabolic processes as key biological processes, with pathways such as biological oxidation and defensins significantly enriched.

CONCLUSION: Significant differences in gene expression are observed between schizophrenia patients with and without MetS. Individual variability in clozapine-induced MetS may be linked to DEGs.

PMID:41523972 | PMC:PMC12781211 | DOI:10.31083/AP49352