Nevin Manimala

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Jun;41(6):531-535.

ABSTRACT

Objective To investigate the causal relationship between serum total bile acid (TBA) levels and gastric cancer (GC) using regression discontinuity design (RDD). Methods A total of 1244 GC patients and 1333 healthy controls were included in the study. Demographic characteristics, gallbladder disease history, tumor markers, and serum TBA levels were collected from both groups. Logistic regression was used to construct a risk prediction model to estimate the risk of GC. RDD was employed with serum TBA as the grouping variable and the individual risk of developing GC as the outcome variable. Results The predictive factors in the GC risk prediction model included age, sex, body mass index(BMI), serum TBA, carcinoembryoniv antigen(CEA), alpha fetoprotein(AFP), carbohydrate antigen 199(CA199), and CA125. Serum TBA was identified as an independent risk factor for GC (OR=1.054, 95% CI: 1.030 to 1.079). RDD analysis indicated that when serum TBA levels reached 8 μmol/L, the probability of developing GC increased sharply by 23.7%. The breakpoint remained statistically significant following validity and robustness assessments. Conclusion The study demonstrates a positive causal relationship between serum TBA levels and GC, when the serum TBA level reaches 8 μmol/L, the risk of an individual developing GC increases sharply.

PMID:40525341

J Prim Care Community Health. 2025 Jan-Dec;16:21501319251346102. doi: 10.1177/21501319251346102. Epub 2025 Jun 17.

ABSTRACT

Adverse childhood experiences (ACEs) can have lasting effects into adulthood. This study examines the relationship between ACEs and the frequency of substance use among high school students in the United States. Data were drawn from the 2023 Youth Risk Behavior Survey, a nationally representative survey of high school students. A cumulative ACE score was calculated based on 8 self-reported lifetime experiences. Multinomial logistic regression models were used to analyze the association between cumulative ACEs and substance use (alcohol, binge drinking, cannabis, and e-cigarettes). A significant positive association was found between cumulative ACEs and substance use. Higher ACE scores were associated with greater odds of substance use across all categories. Specifically, cumulative ACEs were associated with more frequent alcohol use (OR = 1.89, 95% CI = 1.48, 2.43), binge drinking (OR = 1.69, 95% CI = 1.40, 2.05), cannabis use (OR = 1.81, 95% CI = 1.65, 1.99), and e-cigarette use (OR = 1.89, 95% CI = 1.78, 2.00). Similar results were observed for occasional alcohol use (OR = 1.47, 95% CI = 1.31-1.66), binge drinking (OR = 1.53, 95% CI = 1.36-1.72), cannabis use (OR = 1.26, 95% CI = 1.01-1.57), and e-cigarette use (OR = 1.60, 95% CI = 1.32-1.94). This study highlights the significant associations between ACEs and substance use behaviors among adolescents. Addressing ACEs through comprehensive strategies, such as fostering supportive relationships, may be beneficial and promote healthier development.

PMID:40525333 | DOI:10.1177/21501319251346102

J Prim Care Community Health. 2025 Jan-Dec;16:21501319251346702. doi: 10.1177/21501319251346702. Epub 2025 Jun 17.

ABSTRACT

BACKGROUND: Effective hypertension management requires long-term lifestyle and medication adherence facilitated by regular physician. Higher continuity of care (CoC) is postulated to lead to better outcomes.

OBJECTIVES: This study compares health outcomes of patients with hypertension receiving CoC from single family physicians over 5-year period with those treated by multiple physicians.

METHODS: Retrospective cohort study was conducted using electronic medical records from multi-ethnic Asian adults with hypertension and other non-communicable diseases. Patients managed in Family Physician Clinic (FPC) across 7 Singapore public primary care polyclinics from 2015 to 2019 were propensity scores matched with those treated by multiple physicians in General Clinic (GC) of the same polyclinics. CoC Index (COCI), health outcomes including blood pressure (BP), LDL-Cholesterol (LDL-C), cardiovascular complications and preventive measures were compared until 2021.

RESULTS: Analysis of 6520 patients (mean age 64.8 years, 56% female, 76% Chinese) showed FPC cohort had higher COCI (mean = 0.432 vs 0.073; P < .001). This was associated with further reduction in diastolic BP of 0.13 mmHg (P < .001) and LDL-C levels of 0.01 mmol/L (P = .001) per year faster than in GC, with higher proportion of patients meeting LDL-C targets (74.1% vs 68.0%; P < .001) in 2021. FPC cohort also showed greater influenza (OR = 2.88; P < .001) and pneumococcal (OR = 1.34; P < .001) vaccinations uptake. Subgroup analysis of patients with diabetes indicated better diabetic foot screening completion (OR = 1.34; P < .001). No significant improvement was found in systolic BP or cardiovascular complications.

CONCLUSION: Higher CoC in FPC led to clinically relevant improvement in LDL-C and vaccination, but not BP or cardiovascular complication rates.

PMID:40525332 | DOI:10.1177/21501319251346702

Head Neck. 2025 Jun 17. doi: 10.1002/hed.28215. Online ahead of print.

ABSTRACT

BACKGROUND: Time/resource constraints might preclude a randomized controlled trial. Single-arm oncology trials with historical controls are an alternative. With causal inference, treatment effect estimates can be computed in the absence of randomization.

METHODS: From a single-arm trial of 39 head and neck squamous cell carcinoma patients treated with adjuvant nivolumab, we compare 2-year disease-free survival (DFS) to untreated historical controls. We resort to the potential outcomes framework known as Rubin’s causal model (RCM). For time-to-event outcomes, RCM relies upon survival analysis regression with baseline covariates. We contrast the average treatment effect (ATE) estimated by three survival methods: Cox proportional hazards (CPH) versus machine learning alternatives, random survival forests (RSF), and Bayesian Additive Regression Trees (BART).

RESULTS: The ATE in favor of nivolumab: CPH 0.202 (0.098-0.306); RSF 0.159 (0.070-0.248); and BART 0.268 (0.126-0.406).

CONCLUSIONS: The uncertainty is considerable, yet all three methods show nivolumab is superior to control.

PMID:40525328 | DOI:10.1002/hed.28215

Eur J Ophthalmol. 2025 Jun 17:11206721251349867. doi: 10.1177/11206721251349867. Online ahead of print.

ABSTRACT

BackgroundMitochondrial genes regulate lipid metabolism and both are associated with the pathology of glaucoma. Here, we studied the genetic association of mitochondrial genes involved in lipid metabolic pathways with glaucoma and its ocular quantitative traits (QTs).MethodsPolymerase chain reaction based direct sequencing followed by MITOMAP analysis was performed for NADH (MT-ND1, MT-ND2, MT-ND5 and MT-ND6); Adenosine triphosphate (ATP) synthase (MT-ATPase6) and Cytochrome B subunit (MT-CYB) genes in Primary Open angle glaucoma (POAG), closed angle glaucoma (PACG) patients (N = 50 in each group) and unrelated healthy controls (N = 150). The effect of variations on protein stability was analyzed in Dynamut2 and I-Mutant2.0 server. Linear regression analysis was performed for the association of mtDNA variations with QTs.ResultsWe observed 57% of unique segregating sites in patients, that were comparatively higher in MT-ND6 gene. Six common mtSNPs were statistically significant and further associated with VCDR [(m.13469T > A (MT-ND5), m.8860A > G (MT-ATPase6), m.15326A > G (MT-CYB)]. Insilico analysis showed that the disease associated variations in MT-ND5 and MT-ND6 genes decreased protein stability and loss of hydrophobic interaction. Gene expression analysis showed a higher connectivity for MT-ND5 gene with SORT1 and TMBIM6 gene.ConclusionOur results showed a significantly higher mutation rate in MT–ND6, MT-CYB and NT-ND5 genes in patients and also suggested a possible association between the mtSNPs and QTs. Lack of functional studies and insufficient lipid profile data to validate the study results limits the study findings and are to be addressed further in an increased sample size.

PMID:40525318 | DOI:10.1177/11206721251349867

Brain Behav. 2025 Jun;15(6):e70635. doi: 10.1002/brb3.70635.

ABSTRACT

AIM: This study aims to determine the effects of Emotional Freedom Techniques (EFT) on sexual dysfunction and self-care in women diagnosed with multiple sclerosis (MS).

METHOD: This study was conducted using a pretest-posttest experimental design, including follow-up assessments to evaluate the sustainability of the intervention effects. The sample consisted of 16 women aged between 19 and 49 years who were diagnosed with MS and presented to the neurology clinic of a university hospital in Türkiye between October 2023 and September 2024. Data collection instruments included the Personal Information Form (PIF), Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and Self-Care Management Process in Chronic Illness (SCMP-G). Repeated measures analysis of variance (ANOVA) was employed to analyze changes in sexuality and self-care over time. Statistical significance was set at p < 0.05.

RESULTS: Participants received two EFT sessions per month, each lasting 60 min, together with affirmation sessions conducted at least twice a week for 10-15 min. The mean scores of all subdimensions of the MSISQ-19 reached the lowest levels by the seventh week following EFT intervention, with significant differences between time points (p < 0.05). Even though an improvement was observed in the social protection dimension of self-care, the mean scores for the self-protection subdimension decreased.

CONCLUSION: The application of EFT demonstrated positive effects on sexual functioning and self-care levels in women with MS. Therefore, EFT can be integrated into the holistic care processes of patients with MS.

PMID:40525294 | DOI:10.1002/brb3.70635

Am J Hum Biol. 2025 Jun;37(6):e70083. doi: 10.1002/ajhb.70083.

ABSTRACT

INTRODUCTION: Metabolic syndrome (MS) is a group of related physio-biochemical factors that greatly increase the risk of cardiovascular diseases, stroke, and overall mortality. The physio-biochemical factors associated with MS have been previously found to have a genetic basis. Recently, the Fat Mass and Obesity-Associated (FTO) gene has been found to have a significant role in obesity.

OBJECTIVE: To determine the association of FTO gene rs9939609 polymorphism with MS in two rural communities of Assam, Northeast India, having different ancestry.

METHODS: A cross-sectional study was conducted among unrelated adult male and female individuals of the Mising and Ahom communities of Dhemaji district, Assam. Genotyping for the FTO gene’s rs9939609 polymorphism was performed on a subset of participants. Individuals with MS were cases, while controls were randomly chosen from those without MS. Participants were categorized into AA and TA/TT groups. The chi-square test was utilized to assess whether there is any significant difference in the distributions of various categorical variables across the FTO rs9939609 gene variants (AA and TT/TA). Logistic regression was conducted to assess the relationship between the FTO rs9939609 SNP and the risk of MS. All statistical analyses were performed using IBM SPSS Statistics 26.

RESULTS: Individuals with the AA genotype were found to have significantly higher odds of developing MS than those with TA or TT genotypes, after adjusting for all sociodemographic, behavioral, physiological, biochemical, anthropometric, and body composition measures.

CONCLUSION: The present study indicated that variations within the FTO locus (specifically rs9939609) were associated with MS and its components among the Mising and Ahom communities.

PMID:40525286 | DOI:10.1002/ajhb.70083

J Prim Care Community Health. 2025 Jan-Dec;16:21501319251346096. doi: 10.1177/21501319251346096. Epub 2025 Jun 17.

ABSTRACT

OBJECTIVES: Endometrial cancer incidence and mortality disproportionately affect Black patients, and delayed diagnosis is a contributor. Providers in multiple settings share the task of endometrial cancer diagnosis. The purpose of this study is to elicit physician perspectives on national guidelines for the diagnosis of endometrial cancer (EC), understanding of racial disparities in EC, and to explore physician receptivity to a risk-based, endometrial biopsy (EMB)-first approach of peri/postmenopausal bleeding.

METHODS: We performed semi-structured interviews with 12 U.S. physicians across multiple specialties. Interview structure was developed and refined using an iterative process. We used inductive reasoning to employ exploratory content analysis.

RESULTS: We interviewed OB/Gyn (n = 4), family medicine (n = 3), internal medicine n = 3), and emergency medicine (n = 2) physicians in all regions of the U.S. Slightly over half (58%) performed EMB. Most (58%) were uncertain about guidelines for diagnosis. Nearly half (42%) reported lack of knowledge regarding racial disparities in EC diagnosis and cancer outcomes. OB/Gyn physicians were skeptical of guideline efficacy in high-risk patients, including patients identifying as Black. Most (75%) physicians supported a risk-based, biopsy-first approach to diagnosis of EC.

CONCLUSIONS: Physicians caring for patients at risk for EC lack knowledge of current guidelines and of racial disparities in endometrial cancer diagnosis and outcomes. A multi-pronged approach, incorporating changes to national guidelines and targeted provider education, is necessary to eliminate inequities in diagnosis of EC.

PMID:40525285 | DOI:10.1177/21501319251346096

J Exp Biol. 2025 Jun 15;228(12):jeb250243. doi: 10.1242/jeb.250243. Epub 2025 Jun 17.

ABSTRACT

Many invertebrates voluntarily lose (autotomize) limbs during antagonistic encounters, and some regenerate functional replacements. Because limb loss can have severe consequences on individual fitness, it is likely subject to significant selective pressures, making this an excellent phenomenon with which to investigate biomechanical robustness. Spiders frequently autotomize one or more legs. We investigated the time course of locomotor recovery after leg loss and regeneration in juvenile tarantulas (Arachnida: Araneae) naive to autotomy. We recorded high-speed video of spiders running with all legs intact, then immediately after, and again 1 day after they had autotomized two legs. The legs were allowed to regenerate, and the same sequence of experiments was repeated. Video tracking analysis revealed that the spiders resumed their pre-autotomy speed and stride frequency after leg regeneration and in ≤1 day after both autotomies; path tortuosity was unaffected by these treatments. Autotomized spiders widened the spread of their remaining legs for stability and to compensate for missing functional space. To analyze how their gaits changed in response to leg loss, we applied unsupervised machine learning for the first time to measured kinematic data in combination with gait space metrics. Spiders were found to robustly adopt new gait patterns immediately after losing legs, with no evidence of learning. This novel clustering approach both demonstrated concordance with hypothesized gaits and revealed transitions between and variations within these patterns. More generally, clustering in gait space enables the identification of patterns of leg motions in large datasets that correspond to either known gaits or undiscovered behaviors.

PMID:40525284 | DOI:10.1242/jeb.250243

CPT Pharmacometrics Syst Pharmacol. 2025 Jun 17. doi: 10.1002/psp4.70052. Online ahead of print.

ABSTRACT

Furmonertinib demonstrated potent efficacy as a newly developed tyrosine kinase inhibitor for the treatment of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. In vitro research showed that furmonertinib is metabolized to its active metabolite AST5902 via the cytochrome P450 (CYP) enzyme CYP3A4. Furmonertinib is a strong CYP3A4 inducer, while the metabolite is a weaker CYP3A4 inducer. In clinical studies, nonlinear pharmacokinetics were observed during chronic dosing. The apparent clearance showed time- and dose-dependent increases. In this evaluation, a combination of in vitro data using radiolabeled compounds, clinical pharmacokinetic data, and drug-drug interaction (DDI) data of furmonertinib in oncology patients and/or in healthy subjects was used to develop a physiologically based pharmacokinetic (PBPK) model. The model was built in PK-Sim Version 11 using a total of 44 concentration-time profiles of furmonertinib and its metabolite AST5902. Suitability of the predictive model performance was demonstrated by both goodness-of-fit plots and statistical evaluation. The model predicted the observed monotherapy concentration profiles of furmonertinib well, with 32/32 predicted AUC_last (area under the curve until the last concentration measurement) values and 32/32 maximum plasma concentration (C_max) ratios being within twofold of the respective observed values. In addition, 8/8 predicted DDI AUC_last and C_max ratios with furmonertinib as a victim of CYP3A4 inhibition or induction were within twofold of their respective observed values. Potential applications of the final model include the prediction of DDIs for chronic administration of CYP3A4 perpetrators along with furmonertinib, considering auto-induction of furmonertinib and its metabolite AST5902.

PMID:40525261 | DOI:10.1002/psp4.70052