Category: Nevin Manimala

Equine Vet J. 2025 Dec 5. doi: 10.1111/evj.70126. Online ahead of print.

ABSTRACT

BACKGROUND: The widespread assumption that there is minimal potential for pathogen transmission between British racehorse and sport horse populations remains unverified by empirical evidence.

OBJECTIVES: To characterise spatiotemporal patterns of horse attendance at racing and other sport events in Great Britain in 2018.

STUDY DESIGN: Spatiotemporal analysis.

METHODS: Publicly available data from British Horseracing Authority, British Dressage, British Eventing, Endurance GB, and British Showjumping events in Great Britain during 2018 were analysed. Horse attendance was summarised by discipline, month, and season. Venue density was mapped with kernel density estimation. Sport venues within 5 km of racecourses with horse attendance within 24 h of racing were identified and Kulldorff’s spatial scan statistic was used to detect significant time-space clustering of venue use.

RESULTS: Excluding showjumpers, 49,012 horses competed in 8314 events across 598 venues during 2018, generating over 400,000 horse-venue attendances. Most horses (97.2%; n = 47,635/49,012) competed in a single discipline. Venue attendances peaked in summer and were concentrated in southeast England. There were five significant space-time clusters of venue-events within 5 km and 24 h of each other involving 5 racecourses and 8 sport venues. The most likely cluster was in the southeast of England, between January and July, with a relative risk of 62.54.

MAIN LIMITATIONS: Inconsistent horse identification precluded horse-level analysis of showjumping data.

CONCLUSIONS: Racehorse and sport horse populations competing in Great Britain are largely separate, but limited opportunities for local or indirect pathogen spread do exist during peak seasons in areas with high venue density.

PMID:41351275 | DOI:10.1111/evj.70126

HGG Adv. 2025 Dec 4:100552. doi: 10.1016/j.xhgg.2025.100552. Online ahead of print.

ABSTRACT

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study (EWAS) meta-analysis in AA participants from the Jackson Heart Study (JHS, n=1604) and the Multi-Ethnic Study of Atherosclerosis (MESA, n=179) with Illumina EPIC (850k) array data. Linear regression models with methylation as the outcome and continuous BMI as the predictor were stratified by study and sex and meta-analyzed. We identified 208 methylation sites (CpGs, p< 8.72×10^-8) significantly associated with BMI; 151 not been previously reported in literature. Replication was performed in a separate sample of AA participants with 450k array data, which lacks many CpGs present in the 850k array. Replication testing was possible for only 29 of the 151 CpGs; 19 were statistically significant (p<1.72×10^-3). Sex-specific results showed 4 female-only and 3 male-only BMI-CpGs not identified in the sex-combined results. Differentially methylated region (DMR) analysis resulted in 66 DMRs, including several regions near genes previously implicated for obesity (e.g., SOCS3 and TGFB1). Further analyses showed enrichment of genes and traits related to the immune system and inflammation-related pathways (e.g., the IL-6/JAK/STAT pathway).

PMID:41351263 | DOI:10.1016/j.xhgg.2025.100552

Stat Med. 2025 Dec;44(28-30):e70334. doi: 10.1002/sim.70334.

ABSTRACT

With the rapid advancements in wearable device technologies, there is a growing interest in learning useful digital biomarkers from wearable device data as objective, low-cost, real-time alternatives to use in healthcare settings. They have the potential to facilitate disease progression monitoring, medication tailoring, and supplementing clinical trial endpoints. For example, triaxial accelerometer sensor data is promising for monitoring symptoms of movement-related diseases, such as tremors in Parkinson’s disease (PD). However, existing methods for accelerometer studies based on hidden Markov models (HMM) often analyze each individual’s activity data separately, leading to inefficiency and limited generalizability. This paper proposes a joint nonparametric Bayesian method that extends the hierarchical Dirichlet process autoregressive HMM (HDP-AR-HMM) to incorporate subject-specific transition parameters. This approach allows for simultaneous estimation across multiple subjects and repeated measurements, accounts for between-subject variability, and provides consistent hidden state estimation without pre-specifying the number of states. We validate our method on simulated data and show that it can achieve higher accuracy in detecting the true hidden states compared to alternative methods. We apply the method to a free-living study, the Biomarker & Endpoint Assessment to Track Parkinson’s disease (BEAT-PD) DREAM Challenge CIS-PD study, to demonstrate its utility in monitoring disease symptoms in PD patients.

PMID:41351259 | DOI:10.1002/sim.70334

J Obstet Gynaecol Res. 2025 Dec;51(12):e70164. doi: 10.1111/jog.70164.

ABSTRACT

AIM: Previous studies reported inconsistent results on the effects of maternal smoking and drinking on pre-eclampsia (PE). Furthermore, some studies indicated that the development of PE may also be attributable to unhealthy behaviors from men. Hence, this study aimed to evaluate the association between smoking and drinking by couples and PE in the Asian population.

METHODS: A prospective cohort study including 34 104 couples was conducted. Multivariate logistic regression models were used to estimate the odds ratios (ORs) of couples’ smoking and drinking behaviors and their interaction. The assignment score method was used to explore the cumulative effect of adverse behavioral exposures to alcohol and tobacco on PE.

RESULTS: Seven hundred eighty-eight-pregnant women (2.31%) were diagnosed with PE. Maternal active smoking 3 months before pregnancy (OR: 2.010, 95% CI: 1.136-3.555), periconceptional active smoking (OR: 1.560, 95% CI: 1.027-2.368), drinking 3 months before pregnancy (OR: 2.101, 95% CI: 1.397-3.158), and periconceptional drinking (OR: 1.829, 95% CI: 1.318-2.539) were positively associated with PE. Spousal smoking was also a risk factor (OR: 1.174, 95% CI: 1.009-1.366). Additionally, there was an antagonistic effect between maternal active smoking and drinking during the periconceptional period. Moreover, with the increase of bad behaviors of couples, the risk of PE also increased to a certain extent.

CONCLUSIONS: Maternal active smoking and drinking as well as spousal smoking were risk enhancers of PE in the Asian population. We encourage both couples to actively quit smoking and drinking from the beginning of pregnancy preparation.

PMID:41351256 | DOI:10.1111/jog.70164

Clin Pharmacol Ther. 2025 Dec 5. doi: 10.1002/cpt.70158. Online ahead of print.

ABSTRACT

The European Medicines Regulatory Network plays a critical role in safeguarding public health through the assessment and supervision of human medicines. However, rapid scientific and technological advancements have exposed capability deficits across the network, threatening timely and effective regulatory decision-making. To identify the most critical learning needs within the European Medicines Regulatory Network-specifically those related to capability gaps-the EU4Health Joint Action, IncreaseNET, conducted a learning needs analysis. This study presents a learning needs analysis conducted via two complementary approaches: stakeholder collaboration with European Medicines Agency expert committees and a network-wide survey of National Competent Authorities. The analysis identified six priority subject areas requiring urgent capability development: Advanced Therapy Medicinal Products, Biologically Active Substances, Clinical Trials, Modeling and Simulation, Pharmacokinetics, and Statistics. Additional training needs-such as Environmental Risk Assessment and Radiopharmaceuticals-were highlighted through the National Competent Authority survey. Key barriers to capability development include uneven distribution of expertise, limited time for training due to high workloads, and recruitment challenges. The study also revealed methodological variation in how learning needs analyses are conducted across the European Medicines Regulatory Network, underscoring the need for a standardized yet context-sensitive framework. IncreaseNET will pilot innovative training development strategies, including the use of pedagogical specialists, formalized training processes, and targeted expert recruitment initiatives. These efforts aim to build a more agile, capable, and resilient regulatory workforce across Europe.

PMID:41351255 | DOI:10.1002/cpt.70158

Clin Spine Surg. 2025 Oct 31. doi: 10.1097/BSD.0000000000001960. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: To compare the treatment outcomes of lateral lumbar interbody fusion (LLIF) combined with lateral plate fixation (LLIF+LP) and LLIF stand-alone (LLIF-SA).

BACKGROUND: Biomechanical studies suggest that LLIF+LP provides greater biomechanical strength than LLIF-SA. However, limited clinical research has shown no significant differences in fusion and cage subsidence rates between the 2 techniques at follow-up periods longer than 1 year. This study observed the occurrence of a unique fusion pattern, EVB, during the early postoperative period.

MATERIALS AND METHODS: The study included 57 patients in the LLIF-SA group (88 levels) and 68 patients in the LLIF+LP group (110 levels). The outcomes assessed included patient-reported outcomes, cage subsidence rates, fusion rates, lateral cage migration (LCM), and the incidence of EVB at various postoperative time points.

RESULTS: At 6 months postoperatively, the incidence of EVB significantly differed between the 2 groups: 44.9% in the LLIF+LP group and 27.7% in the LLIF-SA group (P<0.05). However, no significant differences were observed at 3 months and 12 months postoperatively (P>0.05). At the end of the follow-up period, the overall fusion rate was comparable between the groups: 98.1% for LLIF+LP and 97.6% for LLIF-SA (P>0.05). No statistically significant difference was found in overall cage subsidence rates, but a significant difference was observed in severe subsidence rates: 27.3% in the LLIF-SA group versus 15.5% in the LLIF+LP group (P<0.05). The LCM rates were 6% in the LLIF-SA group and 0% in the LLIF+LP group (P<0.05).

CONCLUSIONS: Both surgeries yielded satisfactory treatment outcomes. The addition of a lateral plate reduced severe subsidence and lateral migration rates of the cage. While lateral plate fixation did not significantly affect long-term fusion rates, it showed superior fusion advantages in the early postoperative period (6 mo).

PMID:41351240 | DOI:10.1097/BSD.0000000000001960

J Cachexia Sarcopenia Muscle. 2025 Dec;16(6):e70145. doi: 10.1002/jcsm.70145.

ABSTRACT

BACKGROUND: Being underweight is an underrecognized risk factor for mortality among individuals with type 2 diabetes (T2D). This study aimed to evaluate the associations of underweight status with mortality among individuals with T2D.

METHODS: This nationwide, retrospective, population-based cohort study used data from the Korean National Health Insurance Service. We included 1 788 996 adults with T2D who underwent baseline screening between 1 January 2015 and 31 December 2016, with follow-up through December 31, 2022. Underweight was defined as body mass index (BMI) < 18.5 kg/m² and further categorized as mild (17.0-18.4 kg/m²), moderate (16.0-16.9 kg/m²), and severe (< 160 kg/m²). The primary outcome was all-cause mortality analysed using multivariable Cox proportional hazards regression.

RESULTS: During a median follow-up of 6.96 years, 176 056 deaths occurred. Compared with the non-underweight group (BMI ≥ 18.5 kg/m²), all-cause mortality increased stepwise across underweight categories, with adjusted hazard ratios (aHRs) of 2.037 (95% CI, 1.982-2.094) for mild underweight, 2.719 (2.587-2.857) for moderate underweight, and 3.876 (3.646-4.119) for severe underweight. Cause-specific mortality showed similar gradients. For diabetes-related mortality, the aHRs were 2.265 (2.073-2.474), 3.306 (2.845-3.843) and 5.136 (4.300-6.134) across mild, moderate and severe underweight, respectively; for cardiovascular mortality, 1.881 (1.721-2.055), 2.087 (1.751-2.487) and 2.825 (2.267-3.519); and for cerebrovascular mortality, 2.100 (1.881-2.344), 2.300 (1.846-2.866) and 3.501 (2.702-4.537). Notably, the severe underweight group (BMI < 16.0 kg/m²) showed significantly higher all-cause mortality than the severe obesity group (BMI ≥ 35.0 kg/m²) when compared to the BMI 25.0-29.9 kg/m² reference group (aHR [95% CI]: 5.168 [4.857-5.499] vs. 1.504 [1.418-1.595]).

CONCLUSIONS: Among individuals with T2D, underweight status was associated with substantially elevated mortality risks, with severe underweight exhibiting greater risk than severe obesity.

PMID:41351230 | DOI:10.1002/jcsm.70145

Mol Brain. 2025 Dec 5;18(1):90. doi: 10.1186/s13041-025-01258-y.

ABSTRACT

The glymphatic system plays a key role in brain waste clearance, but its genetic regulation remains poorly understood. Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index is a non-invasive imaging biomarker to asses glymphatic system activity. We integrated mean DTI-ALPS genome-wide association study (GWAS) data from 31,021 individuals of European ancestry with GTEx v8 multi-tissue eQTL data to perform transcriptome-wide association studies (TWAS) using Unified Test for Molecular Signature (UTMOST) and Functional Summary-based Imputation (FUSION). Gene-level associations were further validated by Multi-marker Analysis of Genomic Annotation (MAGMA). Causal inference was conducted using cis-Mendelian randomization (cis-MR) and summary-data-based Mendelian randomization (SMR), while colocalization was applied to provide evidence of strong associations between two traits within a single genetic region, thereby ensuring the stability of the MR conclusions. TWAS identified 17 candidate genes (AGBL5-IT1, CENPA, CGREF1, DNAJC5G, EMILIN1, GCAT, KHK, MAPRE3, OTOF, PLCL1, PREB, RBM43, RFTN2, SERPIND1, SNAP29, TRIOBP, and UCN), among which six protein-coding genes (TRIOBP, MAPRE3, EMILIN1, KHK, GCAT, and CGREF1) were further validated by MAGMA. Cis-MR provided evidence for the causal effects of these six genes, while colocalization supported that the MR conclusions were stable for four of them (TRIOBP, MAPRE3, EMILIN1, and GCAT). Finally, SMR identified three genes (TRIOBP, GCAT, and MAPRE3) that showed consistent and robust associations with DTI-ALPS across multiple tissues. These findings provide statistical evidence for genetic regulation of glymphatic function.

PMID:41351017 | DOI:10.1186/s13041-025-01258-y

Eur J Med Res. 2025 Dec 5. doi: 10.1186/s40001-025-03597-x. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults. While cyclophosphamide and cyclosporine are established treatments, rituximab has emerged as a promising alternative. This meta-analysis aims to compare the efficacy of rituximab versus cyclophosphamide and cyclosporine in patients with IMN.

METHODS: A meta-analysis was conducted in accordance with PRISMA guidelines. Databases including PubMed, EMBASE, Cochrane and Web of Science were searched for randomized controlled trials and observational studies comparing rituximab to cyclophosphamide or cyclosporine in adults with biopsy-confirmed IMN. The primary outcome was treatment efficacy (complete or partial remission). Risk of bias was assessed using the Cochrane RoB 2.0 tool. A random-effects model was used for pooling risk ratios. P < 0.05 was considered statistically significant. R software (4.5.0) was used to perform statistical analysis.

RESULTS: A total of eight studies comprising 936 patients were included in the meta-analysis. Rituximab was compared with cyclophosphamide or cyclosporine in idiopathic membranous nephropathy. The overall pooled analysis showed no significant difference in efficacy between treatment groups (RR = 1.117, 95% CI 0.882-1.414, P = 0.3595). Sensitivity analysis confirmed the robustness of the results. Subgroup analysis revealed that rituximab was more effective than cyclosporine in Asian populations, but less effective than cyclophosphamide in patients with severe renal dysfunction. No significant difference in severe adverse events (RR = 0.984, 95% CI 0.744-1.302, P > 0.05) was found between treatments.

CONCLUSION: Rituximab is comparable in efficacy to cyclophosphamide and cyclosporine for IMN treatment, with no significant difference in remission rates or severe adverse events. Treatment should be individualized.

PMID:41351015 | DOI:10.1186/s40001-025-03597-x

BMC Oral Health. 2025 Dec 6. doi: 10.1186/s12903-025-07463-4. Online ahead of print.

ABSTRACT

OBJECTIVES: Panoramic radiographs of twin and non-twin pediatric patients were analyzed to determine the prevalence of developmental dental anomalies. The concordance between monozygotic (MZ) and dizygotic (DZ) twin pairs was assessed to investigate the relative contributions of genetic and environmental factors to these anomalies.

MATERIALS AND METHODS: Panoramic radiographs from 419 pairs of twins and 838 non-twin patients, aged 7 to 13 years, who attended the clinic between 2017 and 2023, were examined for developmental dental anomalies. These anomalies were classified by number, size, shape, and positional anomalies. Categorical data were analyzed using the chi-square test, and the concordance of anomalies within twin pairs was evaluated using pairwise concordance and tetrachoric correlation analyses.

RESULTS: Developmental dental anomalies were observed in 33.2% of the twin group, 23.3% of the control group, 31.4% of the MZ twin group, and 33.8% of the DZ twin group. A statistically significant difference was identified in the prevalence of number anomalies between the twin and control groups (p = 0.025), whereas no significant differences were found for size, shape, and positional anomalies between these groups (p > 0.05). Analysis of MZ twin pairs revealed statistically significant concordance and tetrachoric correlation for anomalies such as hypodontia, dens invaginatus, taurodontism, impacted teeth, and infraoccluded primary molars.

CONCLUSION: The findings of our study indicate that genetic factors play a more significant role in the etiology of hypodontia, taurodontism, impacted teeth, and infraoccluded primary molars.

CLINICAL RELEVANCE: These findings present novel targets for future research aimed at elucidating the genetic and environmental determinants underlying developmental dental anomalies.

PMID:41351006 | DOI:10.1186/s12903-025-07463-4