Search Results (184)

Background/Objectives: Artificial intelligence (AI) offers a promising approach for detecting and classifying symptom severity in patients with Parkinson’s disease (PD). The objective was to provide an overview of AI methods performance used for this classification through a systematic review and meta-analysis conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Methods: The Google Scholar, IEEE Xplore, PubMed/MedLine, and ScienceDirect databases were searched for the period 2015–2025. The studies included were original, peer-reviewed studies written in English that addressed an AI method based on machine learning (ML) or deep learning (DL) for the classification of PD patients. The dataset used had to be “Gait in Parkinson’s Disease,” in which the severity of disease symptoms was assessed using the Hoehn and Yahr (H&Y) scale. Studies had to report at least one of the five performance metrics: accuracy, sensitivity, specificity, precision, and F1 score. Two reviewers independently selected articles, assessed the risk of bias using PROBAST (Prediction Model Study Risk of Bias Assessment Tool), and extracted data. The logit-transformed values were pooled separately by performance metrics and by severity level using a random-effects model. Cochran’s Q test, the I² statistic, and inter-study variability (τ²), computed using the generalized inverse variance method with the restricted maximum likelihood model, were used to assess heterogeneity. Forest plots with 95% confidence intervals were used to present the results. Possible causes of heterogeneity were explored using a subgroup analysis (ML vs. DL) and a sensitivity analysis. Finally, publication bias (Egger’s test) and the certainty of the evidence (using GRADE—Grading of Recommendations Assessment, Development, and Evaluation) were assessed to verify the generalizability of the results. Results: Among the 257 unique records, 12 studies were included. The methods demonstrated very high overall performance (>92%): accuracy (96.4%, 95% CI: 95.9–96.9%), specificity (97.7%, 95% CI: 97.3–98.1%), sensitivity (94.0%, 95% CI: 92.7–95.2%), precision (93.4%, 95% CI: 92.0–94.6%), F1 score (92.1%, 95% CI: 90.6–93.4%). Accuracy, specificity, and precision were high for all H&Y levels. However, the more advanced the symptoms, the lower the sensitivity (97.3% for H&Y0 vs. 92.1% for H&Y3). ML models achieved the best results for classifying healthy patients (H&Y0: 95.7% to 98.2%), while DL approaches performed better for classifying higher severity levels (>92%). Heterogeneity and inter-study variability were moderate (I²: 40–50% and τ²: 0.3–0.4) for precision and F1 score, and high (I² > 90% and τ² > 0.6) for accuracy, specificity, and sensitivity. The GRADE analysis revealed low-quality evidence for precision and F1 score and very-low quality for accuracy, specificity, and sensitivity. Conclusions: Thus, AI-based wearable gait assessment devices show great promise in terms of aiding clinical decision-making and treatment personalization. However, further research using a rigorous methodology (PROBAST) is needed to ensure the generalizability of the results and the clinical viability of the proposed solutions. Full article

Strict minimum message length (SMML) is an information-theoretic coding principle that represents a continuous statistical model by a finite set of assertions and a partition of the sample space. We show that the SMML objective decomposes into assertion entropy and conditional cross-entropy, balancing the cost of identifying an assertion against the cost of encoding data under the assigned model. For any fixed partition, the optimal codepoint for each cell is the model distribution that minimises Kullback–Leibler (KL) divergence from the data distribution restricted to that cell. Using the local Fisher–Rao geometry of regular parametric models, we show that, under a high-resolution LAN-scale regime, SMML partitions are asymptotically the pullback, through the maximum-likelihood estimator, of weighted Fisher–Rao Voronoi tessellations in parameter space, with assertion probabilities appearing as additive weights. For regular canonical exponential families, SMML codepoints satisfy a moment-matching condition and admit an interpretation as KL/Bregman centroids, while exact SMML cells are pullbacks of convex polyhedra in sufficient-statistic space. Together, these results show that SMML induces a natural information-geometric quantisation linking entropy-based coding, KL projection, and divergence-based Voronoi geometry. Full article

Background: Selenium (Sel) supplementation has been proposed as an antioxidant adjunct in Graves’ orbitopathy (GO), with early randomized evidence suggesting benefits in quality of life (QoL), ocular involvement, and disease progression in mild GO. However, subsequent trials across populations with different Sel status and disease severity have yielded inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) reassessed the efficacy of Sel supplementation in GO. Methods: PubMed, Scopus, and the Cochrane Library were searched from inception to 1 May 2026 for RCTs, comparing Sel supplementation with placebo or no Sel supplementation in patients with GO (PROSPERO “CRD420261395074”). Heterogeneity was assessed using I² statistics and Cochran’s Q test. Risk ratios (RRs) were calculated using the Mantel–Haenszel method, and mean differences (MDs) using the Inverse-Variance method. Random-effects models with restricted maximum-likelihood estimation were applied. Results: Five RCTs including 303 patients were analyzed, of whom 165 (56%) received Sel. Sel supplementation was associated with a significant reduction in clinical activity score (MD −1.05; 95% CI −1.61 to −0.48; I² = 52%; p < 0.01). No significant differences were observed in palpebral aperture (MD −0.12; 95% CI −1.22 to 0.98; I² = 58%; p = 0.83), although this anatomical parameter should be interpreted cautiously because it may be influenced by thyroid functional status and hyperthyroidism-related Müller muscle hyperfunction. No significant differences were observed in QoL improvement (RR 1.72; 95% CI 0.43 to 6.92; I² = 86%; p = 0.24) or visual function (MD 6.31; 95% CI −1.40 to 14.03; I² = 45%; p = 0.11). Conclusions: Sel supplementation may improve clinical activity score in patients with Graves’ orbitopathy, but this finding should be interpreted cautiously given the small number of trials, limited sample size, and clinically relevant heterogeneity. Current evidence does not show consistent benefits for palpebral aperture, quality of life, or visual function. Larger RCTs stratified by baseline Sel status and disease severity are needed before firm conclusions can be drawn. Full article

The Gompertz distribution is a well-known lifetime model in survival and reliability analysis, but its hazard rate is restricted to monotone increasing behavior, which limits its applicability to more complex data structures. In this study, we investigate the New Extended Gompertz (NEG) distribution, which is obtained by applying the existing NE-X generator framework to the classical Gompertz baseline distribution. Thus, the NEG model is a special case within an already established generator family rather than an entirely new family of distributions. The main contribution of this paper is not the introduction of a new generator, but rather a comprehensive and systematic investigation of this particular Gompertz-based extension, including its statistical properties, estimation procedures, and practical applications. The proposed model introduces an additional shape parameter that provides increased flexibility in modeling skewness, tail behavior, and hazard-rate structures, allowing for increasing, decreasing, bathtub-shaped, and unimodal hazard patterns under different parameter configurations. Several mathematical properties of the NEG distribution are derived, including explicit expressions for the density, distribution, survival, and hazard-rate functions, as well as moments, entropy measures, and series representations. Parameter estimation is performed using both maximum likelihood and Bayesian approaches, with numerical optimization and Metropolis–Hastings MCMC procedures employed due to the absence of closed-form estimators. The finite-sample behavior of the estimators is investigated through extensive Monte Carlo simulation studies under three different parameter settings. The practical usefulness of the NEG distribution is illustrated using two real datasets on carbon-fiber tensile strength. Comparative results with several competing Gompertz-type models indicate that the NEG distribution provides competitive performance. However, all comparisons should be interpreted within the context of the considered datasets and parameter settings, rather than as claims of universal superiority. The findings suggest that the NEG distribution offers a flexible and practical extension of the Gompertz model for lifetime data analysis. Full article

Background/Objectives: Although current research suggests beneficial effects of dietary supplements on female infertility, existing evidence is often inconsistent and of limited certainty. This systematic review and meta-analysis aimed to investigate the effect of dietary supplements on female infertility in terms of endometrial thickness, pregnancy, live birth, and miscarriage compared to placebo (primary objective) and compared to placebo or a no-treatment comparator (secondary objective). Methods: PubMed, Embase, and CENTRAL were searched up to March 2025. Randomized controlled trials assessing the effect of dietary supplements compared to placebo or a no-treatment comparator among infertile women were included. Screening, data extraction, risk of bias, and certainty of evidence assessments were conducted by two independent reviewers. Data was synthesized quantitatively using random effects restricted maximum likelihood models. Results: Twenty placebo-controlled and 20 no-treatment comparator studies were included. Most studies had some concerns in risk of bias. Primary analyses showed an improvement in endometrial thickness following N-acetyl-cysteine supplementation compared to placebo, while no effect was found for supplements on pregnancy-related outcomes. Certainty of evidence of primary analyses was low. Secondary analyses indicated positive differences in endometrial thickness and pregnancy-related outcomes following supplementation with different supplements compared to placebo and no treatment. Conclusions: This review found no high-certainty evidence that dietary supplements improve female infertility outcomes when compared with placebo. Secondary analyses combining placebo and no-treatment comparator studies generated hypotheses for myo-inositol, N-acetyl-cysteine, vitamin D, vitamin E, and ≥3 substance dietary supplements, but these are at higher risk of bias and require confirmation in adequately powered placebo-controlled trials with live birth as the primary outcome. Full article

Introduction: The declining efficacy of standard triple therapy for Helicobacter pylori (H. pylori) eradication, largely driven by increasing antibiotic resistance, has highlighted the need for alternative treatment strategies. Vonoprazan–amoxicillin dual therapy (VDT) has emerged as a promising regimen due to the potent and sustained acid suppression provided by vonoprazan. This meta-analysis aims to compare the efficacy and safety of VDT versus clarithromycin-based standard triple therapy (STT) for H. pylori eradication in adults. Methods: A systematic search of PubMed, Scopus, and the Cochrane Library was conducted from inception to 15 March 2026 for randomized controlled trials (RCTs) comparing VDT (vonoprazan plus amoxicillin) with STT (proton pump inhibitor, amoxicillin, and clarithromycin) for H. pylori eradication (PROSPERO “CRD420261357715”). Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method within a restricted maximum-likelihood random-effects model. Results: Five RCTs were included with 1363 patients (VDT: 680, STT: 683). VDT demonstrated a significantly higher H. pylori eradication rate compared with STT (RR 1.17; 95% CI [1.07; 1.27]; p = 0.007; I² = 11%). Conclusions: This meta-analysis suggests that VDT may be associated with higher H. pylori eradication rates than clarithromycin-based STT. Further large, well-designed RCTs are needed before firm first-line recommendations can be made. Full article

Background/Objectives: Evidence for herbal ergogenic aids remains uncertain, and ashwagandha trials span heterogeneous performance domains. This review evaluated oral Withania somnifera supplementation on exercise performance and explored participant-, outcome-, formulation-, and supplementation-related moderators. Methods: PubMed, Web of Science, Cochrane Library, Embase, and SPORTDiscus-EBSCO were searched from inception to 1 April 2026. Eligible randomized controlled trials compared oral ashwagandha with placebo or control conditions and reported objective exercise-performance outcomes. Dependent effects were synthesized using restricted-maximum-likelihood three-level random-effects models; 95% prediction intervals, GRADE certainty ratings, subgroup analyses, and dose/duration meta-regressions were reported. Results: Thirteen trials involving 599 participants contributed 79 effect sizes. Samples were mainly young adults or athletes; reported ages included one 18–40-year trial and one late-adolescent athlete cohort aged 17.4 ± 1.7 years. Trial-level sex composition was four male-only, one female-only, three mixed-sex, and five incompletely reported cohorts. Ashwagandha improved overall exercise performance on average (Hedges’ g = 0.47, 95% CI [0.25, 0.69], p < 0.001; I² = 60%; 95% prediction interval [−0.40, 1.33]), but the prediction interval crossed zero. Exercise type was the clearest moderator (P_between = 0.006): evidence was most consistent for aerobic endurance (g = 0.54, 95% CI [0.22, 0.85], p = 0.002), whereas strength effects were positive but uncertain and power or muscular endurance evidence remained sparse. Dose analyses were hypothesis-generating; 500–600 mg/day was the most evidence-supported extract-dose range. Conclusions: Oral ashwagandha may improve selected exercise-performance outcomes, particularly aerobic endurance, but benefits are not uniform across contexts. Future trials should be preregistered, adequately powered, double-blind, formulation-standardized, sex-stratified, and include rigorous blinding checks, mechanistic endpoints, adverse-event monitoring, and sport-specific performance tests. Full article

Background: Oxycodone is a widely prescribed semi-synthetic opioid central to pain management. However, establishing its role in death when detected in postmortem toxicology is challenging. Quantitative evidence to support forensic interpretation remains limited. Methods: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. PubMed and Scopus were searched through 3 March 2026, for studies reporting quantitative postmortem oxycodone concentrations in human biological matrices. Peripheral blood was predefined as the primary matrix for quantitative synthesis. Random-effects meta-analysis with restricted maximum likelihood estimation was performed on logarithmically transformed concentrations to compare fatal intoxications versus non-intoxication deaths and mono- versus mixed-intoxication cases. Pooled estimates were reported as geometric mean concentrations with 95% confidence and prediction intervals. Secondary analyses evaluated metabolite-to-parent ratios, alternative matrices, and postmortem interval (PMI). Results: Twenty-three studies comprising 4335 oxycodone-positive decedents were included in the qualitative synthesis, and 14 studies in the quantitative meta-analysis. Fatal intoxication cases (n = 1555) showed a pooled geometric mean peripheral blood oxycodone concentration of 0.37 mg/L (95% CI: 0.24–0.58; I² = 93.5%), compared with 0.08 mg/L (95% CI: 0.04–0.15; I² = 98.5%) in non-intoxication deaths (n = 1409). Mono-intoxication cases (n = 135) exhibited higher concentrations (0.52 mg/L; 95% CI: 0.22–1.21; I² = 82.3%) than mixed-drug fatalities (n = 511; 0.29 mg/L; 95% CI: 0.13–0.65; I² = 93.1%). Metabolite data indicated that noroxycodone and oxymorphone patterns may assist in distinguishing acute intake and metabolic variability. Alternative matrices, particularly vitreous humor and solid tissues provided complementary interpretative information, while PMI contributed concentration variability. Conclusions: The key quantitative findings of this meta-analysis indicate higher peripheral blood oxycodone levels in fatal intoxications than in non-intoxication deaths. However, substantial heterogeneity precludes the definition of absolute concentration cut-offs, emphasizing the need to approach postmortem oxycodone interpretation within a probabilistic forensic framework integrating circumstantial evidence, sampling time, metabolite ratios, and data from alternative biological matrices. Full article

Background: Resveratrol is a plant-derived polyphenol with reported anti-inflammatory activity, and the MCP-1/CCL2 axis is a key mediator of monocyte recruitment and inflammatory tissue remodeling. Although individual preclinical studies have examined resveratrol effects on MCP-1/CCL2-related outcomes, the overall in vivo evidence has not been quantitatively synthesized. This systematic review and meta-analysis evaluated whether resveratrol treatment is associated with reduced MCP-1/CCL2-related inflammatory readouts in animal models. Methods: The protocol was registered in PROSPERO (CRD420261339126), and reporting followed the PRISMA 2020 statement. PubMed was searched from inception to 12 March 2026, with additional reference-list screening. Eligible studies were in vivo animal experiments comparing resveratrol-treated and control groups with extractable quantitative MCP-1/CCL2-related outcomes. Effect sizes were calculated as Hedges’ g with 95% confidence intervals and pooled using random-effects models fitted by restricted maximum likelihood. Subgroup, sensitivity, cumulative, influence, funnel-plot, dose meta-regression, and SYRCLE-based risk-of-bias analyses were conducted. Results: Twenty-seven studies contributing 29 analyzable datasets were included. The overall pooled effect was −3.74 (95% confidence interval, −4.50 to −2.98), indicating lower MCP-1/CCL2-related readouts in resveratrol-treated groups than in controls, with substantial heterogeneity (I2 = 78.9%). The negative association was driven mainly by rat and mouse datasets, whereas the piglet estimate was directionally opposite and the rabbit estimate came from a single dataset. Funnel-plot inspection suggested asymmetry, and dose meta-regression did not significantly explain between-study variation (slope = −0.17, p = 0.482). Leave-one-out and cumulative analyses indicated directional stability but did not resolve the underlying heterogeneity. Conclusions: These preclinical data indicate lower MCP-1/CCL2-related readouts after resveratrol treatment, but high heterogeneity, PubMed-only retrieval, and pharmacokinetic limitations limit direct clinical inference. Full article

Introduction: Chronic kidney disease represents a significant global health burden, with dialysis as the most prevalent modality for end-stage kidney disease (ESKD) treatment. One of the major causes of ESKD is diabetes mellitus. Diabetic patients undergoing dialysis have higher mortality risk so optimal timing for its initiation is critical in maximizing survival and quality of life. This study aimed to explore the mortality risk of early versus late dialysis initiation in ESKD patients with diabetes. Methods: Systematic searches were conducted according to the PRISMA 2020 guidelines on PubMed, Scopus, ProQuest, and several databases through Web of Science up to 20 May 2025 (PROSPERO CRD420251074686). Effect sizes were presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and 95% prediction intervals (PIs), pooled using a restricted maximum likelihood random-effects model. Subgroup and meta-regression analyses were also performed to search for potential confounding variables. Results: Eight studies involving 303,116 patients were included. Two studies defined early and late dialysis initiation using an estimated glomerular filtration rate (eGFR) cut-off of 5.0 mL/min/1.73 m², while the remaining studies used cut-offs ranging from 7.0 to 7.7 mL/min/1.73 m². The pooled hazard ratio (HR) showed no significant difference in the mortality risk between early and late initiation of dialysis in ESKD patients with diabetes mellitus (HR 1.02, 95% CI 0.79–1.31, p = 0.90, I² = 97.87%, 95% PI 0.45–2.32). Sensitivity analysis showed that the pooled HR was robust. Subgroup analysis demonstrated no significant difference in the pooled HR according to different study designs. Meta-regressions also showed that the year of population sampling, mean age, and follow-up duration of mortality risk did not have significant associations with the pooled HR. Conclusions: Early dialysis initiation does not appear to confer a survival benefit in ESKD patients with diabetes mellitus. However, given the limited and heterogeneous evidence, further high-quality studies are needed. We suggest that dialysis initiation in this specific population should be guided by clinical indications. Full article

Bladder cancer is a molecularly heterogeneous malignancy in which biomarker-driven therapies increasingly shape clinical management. Fibroblast growth factor receptor 3 (FGFR3) alterations and nectin-4 expression are key therapeutic targets, yet their integrated biological and clinical relevance remains unclear. A systematic search of PubMed, Scopus, and Cochrane Central was conducted from database inception to 22 February 2026 (PROSPERO: CRD420261309413). Studies reporting the prevalence of FGFR3 alterations and/or nectin-4 expression in bladder cancer were included. Proportions were pooled using a random-effects model with restricted maximum likelihood and Freeman–Tukey transformation. Heterogeneity was assessed with I² and Cochran’s Q. Fourteen studies (three randomized and 11 observational), including 3955 patients (mean age: 67.34 years), were analyzed. The pooled prevalence of FGFR3 alterations was 52% (95% CI: 23.33–80.12; I² = 99%), while that of nectin-4 expression was 78% (95% CI: 64.23–89.81; I² = 91%). FGFR3 prevalence varied significantly by disease stage, study design, and region, with higher rates in advanced/metastatic disease and randomized trials (p < 0.05). Nectin-4 expression was generally high across included studies, although interpretation was limited by the small number of studies and assay variability. Sensitivity analyses showed the stability of estimates; however, interpretation is limited by substantial heterogeneity. The observed prevalence estimates are strongly influenced by study design, biomarker selection, and assay variability, limiting their interpretation as true biological prevalence. These results should, therefore, be interpreted cautiously and viewed as descriptive rather than definitive estimates. Separate analyses of biomarker-enriched trials and unselected cohorts are necessary to obtain clinically meaningful estimates. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity. Methods: The protocol was registered in PROSPERO (CRD420261360837). PubMed/MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, and CENTRAL were searched from inception to the final search dates. Records were deduplicated in Zotero. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses were estimated using restricted maximum likelihood with Hartung–Knapp adjustment when pooling was appropriate. Results: Across all database sources, 1651 records were identified. After removing 113 duplicate records and 212 records with an ineligible publication type before screening, 1326 records were screened. Seventy-seven reports were sought for retrieval, five were not retrieved, 72 were assessed at full text, and 48 reports corresponding to 35 independent parent trials or trial clusters were retained for qualitative synthesis. The primary kilogram-scale meta-analysis included eight independent comparisons and showed greater body-weight reduction with GLP-1RA/incretin-based therapy delivered within a lifestyle background than with placebo/control (mean difference [MD] −10.08 kg, 95% confidence interval [CI] −12.76 to −7.39; 95% prediction interval [PI] −17.86 to −2.29; I² = 95.6%). Percentage body-weight change was analyzed separately across 11 independent comparisons and also favored GLP-1RA/incretin-based therapy (MD −9.53 percentage points, 95% CI −11.92 to −7.14; 95% PI −17.58 to −1.48; I² = 95.4%). Conclusions: GLP-1RA- and incretin-based therapies delivered within lifestyle interventions are associated with clinically meaningful reductions in body weight in adults with overweight or obesity. Absolute and relative body-weight change metrics should remain analytically separate. The magnitude of benefit varies across trial contexts, and certainty remains limited by risk-of-bias concerns and considerable heterogeneity. Future trials should standardize the reporting of lifestyle co-interventions, body composition, adherence, physical-function outcomes, and safety monitoring. Full article

Background and Aims: Type 2 diabetes mellitus is a recognized risk factor for hepatocellular carcinoma (HCC), particularly in the setting of metabolic dysfunction-associated steatotic liver disease (MASLD), chronic viral hepatitis, advanced fibrosis, and cirrhosis. Beyond hyperglycemia and insulin resistance, diabetic hepatocarcinogenesis is shaped by metabolic inflammation, lipotoxicity, oxidative stress, fibrogenic remodeling, and the cirrhosis-dysplasia-HCC continuum. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may influence several hepatometabolic pathways, but the epidemiologic evidence linking SGLT2i use to HCC risk remains heterogeneous. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating SGLT2i exposure and incident HCC in adults with type 2 diabetes. PubMed, Embase, and the Cochrane Library were searched up to 15 March 2026. Adjusted time-to-event estimates were pooled using a restricted maximum likelihood (REML) random-effects model. The certainty of evidence was assessed using the GRADE framework and judged to be very low. Results: Six observational studies including 526,446 participants were included. SGLT2i exposure was associated with a lower observed risk of incident HCC (pooled HR 0.59, 95% CI 0.45–0.77), but between-study heterogeneity was substantial (I² = 75.2%, τ² = 0.074). The association remained directionally similar after exclusion of Huynh et al. (HR 0.61, 95% CI 0.45–0.81) and in a DPP-4 inhibitor-restricted active-comparator analysis (HR 0.60, 95% CI 0.39–0.92). However, the 95% prediction interval crossed the null (0.25–1.37), indicating that future comparable studies may plausibly show no protective association. Conclusions: SGLT2i exposure was associated with a lower observed risk of incident HCC across available observational studies. However, the certainty of evidence was judged to be very low, and substantial heterogeneity, comparator variation, mixed time-to-event estimands, residual confounding, and a prediction interval crossing the null preclude causal interpretation. These findings should be considered hypothesis-generating rather than practice-changing evidence and support further hepatology-oriented validation. Full article

Introduction: Effective perioperative management in cesarean section remains essential to optimize maternal outcomes. Melatonin (M) has been proposed as a potential adjunct due to its analgesic, anxiolytic, and antiemetic properties; however, evidence from randomized controlled trials (RCTs) remains inconsistent. This meta-analysis aimed to evaluate the efficacy and safety of preoperative melatonin compared with placebo in women undergoing cesarean section. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane from inception to 15 March 2026 for studies evaluating pregnant women undergoing elective cesarean section receiving preoperative melatonin versus placebo (P) (PROSPERO “CRD420261355468”). Heterogeneity was assessed using the I² statistic and Cochrane Q test. Risk ratios (RRs) and standardized mean differences (SMDs) were computed using a restricted maximum-likelihood estimator random-effects method. Trial Sequential Analysis (TSA) was performed to assess the robustness and sufficiency of the evidence. Results: Seven RCTs were included with 552 patients (melatonin: 278; placebo: 274). Preoperative melatonin significantly reduced opioid consumption in the overall pooled analysis (RR 0.31, 95% CI 0.12 to 0.80; p = 0.030; I² = 50%), and TSA supported the robustness of this opioid-sparing finding under the selected assumptions. Postoperative pain scores were also significantly lower in the melatonin group (SMD −2.10, 95% CI −2.43 to −1.78; p < 0.01; I² = 22%). The incidence of postoperative nausea showed a trend toward reduction in the conventional meta-analysis (RR 0.49, 95% CI 0.23–1.04; p = 0.057; I² = 34%); although TSA suggested a possible benefit, this finding should be considered exploratory. No significant difference was observed in intraoperative blood loss (SMD −0.33, 95% CI −1.53 to 0.88; p = 0.60; I² = 94%). Conclusions: Preoperative melatonin may be a promising adjunct in cesarean section, particularly for reducing postoperative pain and overall opioid consumption. TSA findings support the opioid-sparing result under selected assumptions, while the possible effect on postoperative nausea remains exploratory. Further high-quality trials are warranted before routine clinical implementation can be recommended. Full article

Operational shutdowns following hazardous liquid pipeline incidents are critical but poorly understood events that impact the U.S. energy supply. Although prior research has investigated the causes and outcomes of pipeline failures, limited work has explained what drives both the likelihood of a shutdown and the duration once it begins. The goal of this study is to address this gap by developing a hurdle regression model to examine the two-stage shutdown mechanism in pipeline incidents, using the Pipeline and Hazardous Materials Safety Administration (PHMSA) incident dataset from 2010 to 2025. The hurdle model consists of a logistic regression restricted to pre-decision predictors to model the probability of shutdown, and a lognormal regression to model the duration of those leading to shutdown. The results revealed that distinct factors are associated with each outcome. Shutdown probability is associated with pre-decision operational and contextual indicators, including operating pressure at the time of incident, accident type, location, monitoring presence, and response delay. In contrast, shutdown duration is associated with logistical complexity and post-incident severity, including incidents at pipeline crossings, pressures exceeding 110% of the maximum operating pressure, and reported property damage. These findings, while exploratory in nature given the use of public incident data, offer practical reference points for operators and regulators who aim to shorten recovery time and strengthen the resilience of energy infrastructure. Full article