Nevin Manimala

J Comput Biol. 2025 Dec 5. doi: 10.1177/15578666251392595. Online ahead of print.

ABSTRACT

Reconciliations are a mathematical tool to compare the phylogenetic trees of genes to the species that contain them, accounting for events such as gene duplication and loss. Traditional reconciliation methods have predominantly relied on parsimony to infer gene-only evolutionary events and usually make the hypothesis that genes evolve independently. Recently, more advanced models have been developed that account for complex gene interactions stemming from phenomena such as segmental duplications, where multiple genes undergo simultaneous duplication. In this article, we study the NP-hard problem of reconciling gene trees to a species tree with segmental duplications, without the aid of synteny information. We address this problem by proposing a novel probabilistic approach, imposing a Boltzmann distribution over the space of reconciliations. This allows for a Gibbs sampling-like Markov chain Monte Carlo algorithm that uses simulated annealing to effectively find or approximate the most parsimonious reconciliation, as demonstrated through rigorous simulations and re-analysis of empirical datasets. Our findings present a promising new framework for addressing NP-hard reconciliation challenges in phylogenetics, enhancing our understanding of gene evolution and its relationship with species evolution.

PMID:41433090 | DOI:10.1177/15578666251392595

Mol Hum Reprod. 2025 Dec 23:gaaf061. doi: 10.1093/molehr/gaaf061. Online ahead of print.

ABSTRACT

Endometriosis (EM) is a debilitating disease involving the growth of endometrial glands and stroma outside the uterus. To further our understanding of epigenomic dysregulation in EM and search for disease biomarkers, we performed a comprehensive evaluation of DNA methylation in eutopic endometrium (EE) and EM lesions. We undertook deconvolution analysis of DNA methylation data previously generated from endometrial aspirate biopsies obtained from 637 EM cases and 347 controls using microarray-based DNA methylation analysis. We further analyzed DNA methylation in EM lesions and paired EE samples via solution phase hybridization and DNA sequencing. For analysis of microarray data, we used a reference-free approach (BCconf) to recover latent factors and found high correlation with EM status, suggesting EE cell proportions vary between EM cases and controls. Deconvolution revealed that epithelial cells (p-value = 9.1 × 10-3) and fibroblasts (p-value = 0.022) were reduced in EM cases. Deconvolution of the sequencing data identified differences between EM lesions and EE of cases and controls, including vascular endothelial cells (false discovery rate [FDR]-adjusted p-value = 6.1 × 10-3; more abundant in EM lesions), natural killer cells (FDR-adjusted p-value = 0.031; less abundant in EM lesions) and ovarian/endometrial epithelium (FDR-adjusted p-value = 3.2 × 10-3). We detected significant differences in cell type proportion between EE samples of cases and controls. Improved reference data for de convolution to inform more intelligent region targeting approaches will provide further insight into the molecular phenotype of EM and may inform novel approaches for minimally invasive detection.

PMID:41433079 | DOI:10.1093/molehr/gaaf061

JMIR Form Res. 2025 Dec 23;9:e68282. doi: 10.2196/68282.

ABSTRACT

BACKGROUND: The clinical and cost-related consequences of internet-based depression screening, in combination with automated feedback, have been rarely investigated. We aimed to conduct a cost-effectiveness analysis of DISCOVER, a 3-armed, observer-masked, randomized controlled trial that focused on 2 versions of automated feedback interventions after internet-based depression screening.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of automated nontailored and tailored feedback interventions after internet-based depression screening from a societal perspective.

METHODS: Participants were recruited from the general population via traditional and social media. Participants who were undiagnosed but screened positive for depression on an online version of the Patient Health Questionnaire-9 (≥10 points) were randomized to automatically receive no feedback, nontailored feedback, or tailored feedback. The feedback interventions included the depression screening result, a recommendation to seek professional advice, and brief general information about depression. The tailored feedback was additionally framed according to the participants’ symptom profiles, treatment preferences, health insurance plans, and local residency. The time horizon was 6 months. The main outcome was the incremental cost-effectiveness ratio (ICER) from a societal perspective using quality-adjusted life years (QALY) based on the EuroQol-5D-5L. Cost-effectiveness acceptability curves were constructed. Furthermore, several sensitivity analyses and explorative subgroup analyses were conducted.

RESULTS: A total of 1012 participants (no feedback: n=343, 33.9%; nontailored feedback: n=338, 33.4%; and tailored feedback: n=331, 32.7%) were included. Differences in costs and effects were not statistically significant. However, ICER results indicated that both no feedback and tailored feedback exhibited dominance over nontailored feedback. The ICER of tailored feedback compared to no feedback was €109,730 per QALY (a currency exchange rate of €1=US $1.02 was applicable as of December 31, 2022), whereas both costs and QALYs were lower in tailored feedback. The cost-effectiveness probability of tailored feedback compared to no feedback ranged between 41% and 80%. Sensitivity analyses exhibited similar trends.

CONCLUSIONS: Six months postintervention, feedback interventions had no statistically significant effect on costs from a societal perspective or on QALYs. Tailored feedback was associated with moderate cost-effectiveness probabilities compared to no feedback. Explorative subgroup analyses revealed subpopulations for which the interventions might be cost-effective.

PMID:41433057 | DOI:10.2196/68282

JMIR Med Educ. 2025 Dec 23;11:e78857. doi: 10.2196/78857.

ABSTRACT

BACKGROUND: Virtual simulated patients (VSPs) powered by generative artificial intelligence (GAI) offer a promising tool for training clinical interviewing skills; yet, little is known about how different system- and user-level variables shape students’ perceptions of these interactions.

OBJECTIVE: We aim to study psychology students’ perceptions of GAI-driven VSPs and examine how demographic factors, system parameters, and interaction characteristics influence such perceptions.

METHODS: We conducted a total of 1832 recorded interactions involving 156 psychology students with 13 GAI-generated VSPs configured with varying temperature settings (0.1, 0.5, 0.9). For each student, we collected age and sex; for each interview, we recorded interview length (total number of question-answer turns), number of connectivity failures, the specific VSP consulted, and the model temperature. After every interview, students provided a 1-10 global rating and open-ended comments regarding strengths and areas for improvement. At the end of the training sequence, they also reported perceived improvement in diagnostic ability. Statistical analyses assessed the influence of different variables on global ratings: demographics, interaction-level data, and GAI temperature setting. Sentiment analysis was conducted to evaluate the VSPs’ clinical realism.

RESULTS: Statistical analysis showed that female students rated the tool significantly higher (mean rating 9.25/10) than male students (mean rating 8.94/10; Kruskal-Wallis test, H=8.7; P=.003). On the other side, no significant correlation was found between global rating and age (r=0.02, 95% CI -0.03 to 0.06; P=.42), interview length (r=0.04, 95% CI -0.2 to 0.10; P=.18), or frequency of participation (Kruskal-Wallis test, H=4.62; P=.20). A moderate negative correlation emerged between connectivity failures and ratings (r=-0.26, 95% CI -0.41 to -0.10; P=.002). Temperature settings significantly influenced ratings (Kruskal-Wallis test, H=6.93; P=.03; η²=0.02), with higher scores at temperature 0.9 compared with 0.1 (Dunn’s test, P=.04). Concerning learning outcomes, self-perceived improvement in diagnostic ability was reported by 94% (94/100) of students; however, final practical examination scores (mean 6.67, SD 1.42) did not differ significantly from those of the previous cohort without VSP training (mean 6.42, SD 1.56). Sentiment analysis indicated predominantly negative sentiment in GAI responses (median negativity 0.8903, IQR 0.306-0.961), consistent with clinical realism.

CONCLUSIONS: GAI-driven VSPs were well-received by psychology students, with student gender and system-level variables (particularly temperature settings and connection stability) shaping user evaluations. Although participants perceived the training as beneficial for their diagnostic skills, objective examination performance did not significantly differ from the previous cohort. However, lack of randomization limits the generalization of the results obtained, and further experiments are required.

PMID:41433050 | DOI:10.2196/78857

J Int Soc Sports Nutr. 2026 Dec 31;23(1):2605338. doi: 10.1080/15502783.2025.2605338. Epub 2025 Dec 23.

ABSTRACT

BACKGROUND: Protein supplements are a popular category of dietary supplements among fitness enthusiasts and athletes. However, research providing definitive conclusions on the effects of protein on athletic performance and post-exercise recovery remains limited. Key factors, such as protein source, timing, and optimal dosage, require further investigation to clarify their impact.

METHOD: A systematic search across seven databases identified 6,129 studies, which were screened using the Covidence online tool. After independent selection, data extraction, and risk of bias assessment by two reviewers, 75 studies involving 1,206 athletes were included in the meta-analysis. A multilevel meta-analysis synthesized data from the included studies using a Bayesian hierarchical model with the brms package. Publication bias was assessed using a funnel plot generated with the PublicationBias package and by calculating the P value of Egger’s test through the metafor package. Additionally, a moderation analysis with the brms package was conducted to examine the relationship between seven moderators and effect sizes.

RESULTS: The results demonstrated that the effects of protein-carbohydrate supplements showed statistical significance in comparison to the placebo group [μ(SMD): 0.57, 95% CI: 0.2 to 0.93] in enhancing endurance performance. Pure protein supplements demonstrated statistically significant effects compared to the placebo group in both endurance performance [μ(SMD): 0.37, 95% CI: 0.02 to 0.71] and muscle strength [μ(SMD): 0.72, 95% CI: 0.18 to 1.27]. For post-exercise recovery, pure protein supplements also showed statistically significant effects compared to carbohydrate supplements for maintaining glycogen resynthesis [μ(SMD): 0.83, 95% CI: 0.21 to 1.46]. However, the results indicated that all significant effects were observed in randomized controlled trials where the energy intake between the intervention and control groups was not matched.

CONCLUSION: The effects of protein supplementation on athletic performance and post-exercise recovery appear to be limited. Protein supplements showed beneficial effects compared to no supplementation. However, all statistically significant results were derived from studies in which energy intake was not matched between groups. This suggests that the observed benefits may not be attributable to protein per se. An additional intake of 1 g/kg/day of protein from supplements, resulting in a total daily protein intake of approximately 2 g/kg/day, appears to be most effective for enhancing athletic performance.

REGISTRATION: Registered at the International Prospective Register of Systematic Reviews (PROSPERO) (identification code CRD42024608194).

PMID:41433039 | DOI:10.1080/15502783.2025.2605338

JAMA Surg. 2025 Dec 23. doi: 10.1001/jamasurg.2025.5699. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite the recovery advantages of minimally invasive surgical techniques, moderate to severe pain after laparoscopic colorectal surgery is a common barrier to improving postoperative recovery quality.

OBJECTIVE: To evaluate whether intrathecal morphine (ITM) combined with transversus abdominis plane block (TAPB) improves postoperative recovery quality after laparoscopic colorectal surgery.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, double-blind randomized clinical trial was conducted at Sun Yat-sen University Cancer Center between October 15, 2024, and February 15, 2025. Adults scheduled for elective laparoscopic colorectal surgery were randomized 1:1 to ITM or saline placebo. Data were analyzed from March 1, 2025, to March 31, 2025.

INTERVENTIONS: Both groups received liposomal bupivacaine for TAPB as part of standard enhanced recovery after surgery (ERAS) protocol. The intervention group received ITM, 3 µg/kg, while the control group received intrathecal normal saline.

MAIN OUTCOMES AND MEASURES: The primary outcome was the Quality of Recovery 15 (QoR-15) score at 24 hours postoperatively. Secondary outcomes included postoperative pain scores, cumulative opioid consumption (in morphine milligram equivalents [MME]), time to first flatus, time to first ambulation, incidence of adverse effects, and length of hospital stay.

RESULTS: A total of 252 patients were included in the intention-to-treat analysis (mean [SD] age, 58.4 [11.1] years; 112 female patients [44.4%]). At 24 hours postoperatively, the intervention group had significantly higher mean (SE) QoR-15 scores compared to the control group (114.95 [1.04] vs 102.22 [0.76]; mean difference, 12.21; 95% CI, 9.91-14.51; P < .001), indicating better recovery quality. Postoperative mean (SD) morphine consumption was lower in the intervention group compared to the control group (4.4 [6.4] MME vs 10.4 [11.1] MME; mean difference, -6.59; 95% CI, -8.88 to -4.31; P < .001). The intervention group also had a reduced incidence of nausea (23.8% vs 37.3%; adjusted risk difference, -15.06%; 95% CI, -26.60% to -3.52%; P = .01), but a high incidence of pruritus was observed in the intervention group (19.0% vs 3.2%; adjusted risk difference, 15.08%; 95% CI, 7.26%-22.90%; P < .001).

CONCLUSIONS AND RELEVANCE: Per the results of this randomized clinical trial, in laparoscopic colorectal surgery, ITM combined with TAPB can significantly enhance early postoperative recovery and analgesia, albeit with an increased risk of pruritus. This strategy may be a valuable component of multimodal analgesia regimens following laparoscopic colorectal surgery.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06636864.

PMID:41433024 | DOI:10.1001/jamasurg.2025.5699

J Int Soc Sports Nutr. 2025 Sep 30;22(sup1):2586523. doi: 10.1080/15502783.2025.2586523. Epub 2025 Dec 23.

ABSTRACT

BACKGROUND: Creatine (Cr) supplementation is well established for enhancing fat-free mass (FFM) when combined with resistance training (RT). However, the influence of prior training experience on supplementation efficacy remains unknown.

OBJECTIVE: This systematic review and dose-response meta-analysis of controlled trials evaluated the effects of Cr supplementation combined with RT on body composition, with particular emphasis on the differences between trained (experienced) and untrained (novice) individuals.

METHODS: A systematic search of major databases was conducted to identify controlled trials published until March 2025. The effects of Cr supplementation on body mass, body mass index (BMI), FFM, fat mass (FM), and body fat percentage (BFP) were examined using random-effects meta-analysis.

RESULTS: A pooled analysis of 61 trials revealed that Cr supplementation significantly increased FFM (weighted mean difference [WMD]: 1.39 kg; 95% confidence intereval (CI): 1.07,1.70; p < 0.001) and body mass (WMD: 0.89 kg; 95% CI: 0.76,1.01; p < 0.001) without significant effects on FM, BMI, and BFP. Trained individuals exhibited greater, though non-significant, gains in FFM (1.82 vs. 1.23 kg) compared with untrained participants, despite similar increases in total body mass. Dose-response analyses identified significant relationships between Cr dose and changes in body mass and BMI. Furthermore, supplementation duration was associated with changes in BFP and body mass.

CONCLUSION: Both novice and experienced lifters gained FFM with Cr supplementation compared to placebo. The increase in FFM was approximately 0.6 kg (≈50%) greater in experienced participants; however, this between-group difference was not statistically significant.

PMID:41433021 | DOI:10.1080/15502783.2025.2586523

Mol Neurobiol. 2025 Dec 23;63(1):322. doi: 10.1007/s12035-025-05635-5.

ABSTRACT

Neuroinflammation and oxidative stress contribute significantly to cognitive decline, a hallmark of neurodegenerative diseases such as Alzheimer’s disease (AD). Addressing cognitive decline is a critical medical need, and phosphodiesterase-5 inhibitors (PDE5Is) may offer a promising solution. This meta-analysis highlights the anti-inflammatory and antioxidant actions of PDE5Is, which may help counter neuroinflammation and oxidative stress in neurodegenerative diseases including AD. We reviewed over 1,258 studies and considered 34 preclinical rodent studies of inflammation or oxidative stress. Quantitative data on biomarkers such as Tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), IL-6, NF-κB, IL-10, Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH), Malondialdehyde (MDA), Myeloperoxidase (MPO), and caspase-3 was extracted and analyzed using a random-effects model. Study quality was evaluated with a modified CAMARADES checklist, and heterogeneity was assessed using the I² statistic. PDE5Is treatment significantly lowered pro-inflammatory cytokines and oxidative stress markers, while boosting the levels of critical anti-inflammatory and antioxidant molecules. The pooled standardized mean differences (SMDs) indicated treatment efficacy for nearly all biomarkers. Notably, the studies on Alzheimer’s models confirmed similar therapeutic benefits in reducing amyloid burden and enhancing cognitive outcomes. With a strong safety profile and ability to modulate Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nuclear erythroid-related factor 2 (Nrf2) pathways, PDE5Is offer promising neuroprotective potential. Thus, repurposing PDE5Is may develop new disease-modifying therapies for Alzheimer’s, making clinical investigation crucial.

PMID:41433006 | DOI:10.1007/s12035-025-05635-5

JMIR Res Protoc. 2025 Dec 23;14:e74298. doi: 10.2196/74298.

ABSTRACT

BACKGROUND: Older adults are a rapidly growing demographic and often face social isolation and limited access to outdoor activities due to mobility issues, health conditions, and environmental barriers. These limitations can negatively impact their well-being, leading to reduced physical activity, cognitive decline, and emotional distress. Virtual reality (VR) technology offers a promising solution to bridge this gap by enabling access to immersive virtual environments, which may enhance the quality of life for residents in nursing homes.

OBJECTIVE: The aim of this study is to assess whether the use of VR glasses in nursing homes improves the quality of life of older adults by reducing the challenges they face in participating in recreational activities outside their care facilities.

METHODS: This study will adopt a prospective, longitudinal quasi-experimental design conducted in nursing homes within a basic health area of Catalonia, Spain. The intervention period will span 1 year. Participants will use VR glasses to interact with virtual environments, and their quality of life will be measured using the Rivas-Borda Quality of Life Scale, based on other validated scales.

RESULTS: Outcomes will focus on variations in quality-of-life scores before and after the intervention, as determined by the Rivas-Borda Scale. Statistical analysis will include detailed metrics such as sample size, confidence intervals, and P values to evaluate the intervention’s effectiveness.

CONCLUSIONS: This research seeks to confirm that VR technology can be a valuable tool for enhancing the quality of life in older adults residing in nursing homes, addressing issues like social isolation and limited access to outdoor activities in an innovative and engaging way.

PMID:41432992 | DOI:10.2196/74298

Arch Orthop Trauma Surg. 2025 Dec 23;146(1):16. doi: 10.1007/s00402-025-06161-8.

ABSTRACT

INTRODUCTION: Medial unicompartmental knee arthroplasty (UKA) has become an established alternative to total knee arthroplasty (TKA) for isolated medial compartment osteoarthritis, offering faster recovery and better functional outcomes. However, results during the early phase of institutional adoption may vary depending on surgeon experience and procedural standardization. This study aimed to evaluate early clinical outcomes, complication rates, revision profiles, and the learning curve associated with the initial institutional adoption of medial mobile-bearing UKA in a high-volume, multi-surgeon center.

METHODS: This prospective case series included 154 consecutive medial UKAs performed by five surgeons on 152 patients. Pre- and postoperative KOOS and NPRS were recorded up to a 24-month follow-up, with a 100% follow-up rate. The primary endpoint was improvement in pain and function as measured by NPRS and KOOS. Inclusion/exclusion criteria, surgical technique, and rehab protocol were standardized.

RESULTS: Mean NPRS improved significantly from 7.6 ± 1.4 preoperatively to 1.8 ± 1.9 at 24 months (p < 0.001). Total KOOS increased from 31.0 ± 12.5 to 88.0 ± 13.4 (p < 0.001), with all subscales exceeding the minimal clinically important difference. The two-year revision-free survival rate was 94.8% (95% CI 90.5-97.0%). A total of 9 complications (5.8%) occurred, mostly early technical events related to the initial learning curve, including three bearing dislocations.

CONCLUSION: Medial UKA showed excellent early outcomes with a low revision rate and a complication profile consistent with the expected early technical learning phase. These findings support the safe and effective institutional introduction of medial UKA, emphasizing the importance of structured training and standardized protocols for successful early adoption.

PMID:41432963 | DOI:10.1007/s00402-025-06161-8