Nevin Manimala

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

J Oncol Pharm Pract. 2025 Jun 17:10781552251341569. doi: 10.1177/10781552251341569. Online ahead of print.

ABSTRACT

PurposeThe 10-item Medication Adherence Rating Scale (MARS-10) is a validated, self-report tool used to assess adherence to chronic illnesses due to its applicability. However, its psychometric properties have not been evaluated among cancer patients receiving chemotherapy. This study aimed to determine the psychometric properties of the modified MARS-10 in this population.MethodsA cross-sectional analytic study was conducted on adults receiving cancer chemotherapy from April to May 2022. Confirmatory factor analysis was used to validate the scale. The internal consistency was determined using composite reliability. Convergent and discriminant validity of the constructs were measured by the average variance extracted and the Heterotrait-Monotrait correlation ratio, respectively. Statistical significance was declared as p-value < 0.05.ResultsThree hundred (n = 300) adults receiving cancer chemotherapy were enrolled in the study. There was a significant difference between the higher and lower adherence scores, t (299) = 95.84, p < 0.001. The four constructs explained 66.6% of the total variance. The composite reliability of constructs one (0.79), two (0.66), three (0.66), and four (0.66) was in the acceptable to good range. The extracted mean-variance was more than 0.50, and the Heterotrait-Monotrait correlation ratio ranged from 0.31-0.83 for all constructs.ConclusionThis study has established the internal psychometric properties of the modified 10-item Medication Adherence Rating Scale. Therefore, this modified scale is a valuable tool for researchers and has important implications for oncology health promotion, and policymakers where direct adherence measurement to cancer chemotherapy is challenging.

PMID:40525251 | DOI:10.1177/10781552251341569

Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251350630. doi: 10.1177/15330338251350630. Epub 2025 Jun 17.

ABSTRACT

PurposeTo comprehensively evaluate the efficacy and safety of combining poly (ADP-ribose) polymerase (PARP) inhibitors with chemotherapy in patients with advanced breast cancer.MethodsA systematic literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) evaluating PARP inhibitor-chemotherapy combinations. Studies reporting progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety outcomes were included. Data extraction and quality assessment were performed independently by two reviewers, and a meta-analysis was conducted using random-effects models.ResultsOf 970 studies retrieved, four RCTs involving 1064 patients met the inclusion criteria. PARP inhibitors combined with chemotherapy significantly improved PFS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.84, P < .0001) and showed a trend towards improved OS (HR 0.93, 95% CI 0.79-1.09, P = .36), though this was not statistically significant. There was no significant improvement in ORR (RR 1.08, 95% CI 0.98-1.20, P = .13). Regarding safety, no significant difference was observed in all grades or grade 3-4 adverse events (AEs) overall, but the combination therapy was associated with an increased risk of anemia, nausea, and diarrhea (RRs ranging from 1.14 to 1.29, all P < .01).ConclusionPARP inhibitor combined with chemotherapy is an effective option for the treatment of patients with advanced breast cancer, but its potential increased risks of specific AEs need to be weighed. Clinicians should make individualized treatment plans according to the specific conditions of patients, comprehensive consideration of efficacy and safety.

PMID:40525248 | DOI:10.1177/15330338251350630

J Tradit Chin Med. 2025 Jun;45(3):693-701. doi: 10.19852/j.cnki.jtcm.2025.03.020.

ABSTRACT

OBJECTIVE: To find more influencing factors Qi-deficiency constitution of Traditional Chinese Medicine (TCM) using dynamic and comprehensive information.

METHODS: Because grey relational analysis (GRA) is good at processing incomplete information and has no special requirements for sample size and distribution. We acquired 2122 pieces of valid Qi-deficiency constitution dynamic data after preprocessing, and used GRA combing with χ ² test and multivariate logistic regression analysis to discover and sort the influencing factors of Qi-deficiency constitution.

RESULTS: For the calculation results of GRA, there were 10 (62.5%) aspects whose grey correlation degrees were greater than 0.6. The results of χ ² test showed that all the above 10 aspects were statistically significant with Qi-deficiency constitution. The analysis results of multivariate logistic regression analysis showed the following factors were positively correlated with Qi-deficiency constitution: premature birth, sleeping late and getting up early, sleeping late and getting up late, irregular sleeping, sleeping 6.0-6.9 h per day, artificial feeding, female, age at 18-19, and father’s age at 18-19 years old when a baby at birth. The following factors were negatively correlated with Qi-deficiency constitution: sleeping 8.0-8.9 h per day and ≥ 9.0 h per day, and age at 30-39 and 40-49 years old.

CONCLUSIONS: It is necessary to pay attention to these innate and acquired information of individuals which may lead to Qi-deficiency constitution. And our research also provides a novel methodological thinking for analyzing the influential factors of TCM constitution.

PMID:40524309 | DOI:10.19852/j.cnki.jtcm.2025.03.020