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Nevin Manimala Statistics

Trends, Demographic Characteristics and Seasonal Patterns of Rectal Prolapse Surgery in Japan: A Nationwide Claims-Based Analysis From 2014 to 2023

Ann Gastroenterol Surg. 2026 Jun 26. doi: 10.1002/ags3.70242. Online ahead of print.

ABSTRACT

AIM: This study investigated nationwide trends, demographic characteristics, and seasonal patterns of rectal prolapse surgery in Japan, using healthcare claims databases.

METHODS: Surgical data were extracted from the National Database of Health Insurance Claims (NDB) from 2014 to 2023. Procedures were classified by surgical approach as conventional or laparoscopic. Crude and age-adjusted rates per 100 000 person-years were calculated. Temporal trends were assessed using linear and Poisson regression. Seasonal variations (April 2019-March 2024) were evaluated using one-way analysis of variance with post hoc comparisons, and correlations with meteorological variables were examined using Pearson’s correlation coefficients.

RESULTS: Over the decade, a total of 62 407 overall surgeries were performed, with an average annual rate of 4.7 per 100 000 person-years and an overall female-to-male ratio of 6.9:1. Overall surgery rates peaked at ages 85-89 in males (5.5 per 100 000 person-years) and females (59.1). While age-adjusted overall and conventional surgeries declined significantly, laparoscopic surgeries significantly increased (all p < 0.01). Age-adjusted overall surgery rates declined significantly in both sexes (RR = 0.960 for males, 0.983 for females, and 0.979 overall; each p < 0.0001), particularly among younger women aged 30-39 years (p < 0.0024). The mean seasonal overall surgeries exhibited distinct seasonal variation: 578.0 (SD 99.2) in spring, 440.0 (SD 85.9) in summer, 432.4 (SD 50.8) in autumn, and 544.4 (SD 71.8) in winter, and showed moderate negative correlations with temperature.

CONCLUSION: This study provides contemporary epidemiological insights into surgical management of rectal prolapse in Japan.

PMID:42495686 | PMC:PMC13394726 | DOI:10.1002/ags3.70242

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Nevin Manimala Statistics

Contemporary Regional Disparities in Robotic-Assisted Rectal Resection in Japan: A Nationwide Population-Based Study Using the National Database Open Data

Ann Gastroenterol Surg. 2026 Apr 6. doi: 10.1002/ags3.70220. Online ahead of print.

ABSTRACT

BACKGROUND: Robotic-assisted rectal resection has expanded in Japan since national health insurance reimbursement began in 2018; however, its population-level regional distribution remains unclear. We evaluated temporal trends and contemporary regional disparities using the National Database (NDB) Open Data.

METHODS: We analyzed NDB Open Data for fiscal years 2014-2023. All patients undergoing rectal resection, irrespective of disease etiology, were included. Procedures were classified as open, laparoscopic, or robotic-assisted. We assessed temporal trends and age- and sex-stratified surgical volumes. For 2023, prefecture-level surgical rates per 100 000 population and robotic proportions were calculated. Standardized claim ratios (SCRs) were computed to adjust for age and sex. Population density was used as a proxy for urbanization. Prefectures were categorized into urban and rural groups using the highest and lowest population-density quartiles (middle two quartiles excluded), and robotic proportions were compared using the Mann-Whitney U test as an exploratory analysis.

RESULTS: Robotic-assisted rectal resections increased markedly after 2018, whereas open surgery declined. Substantial inter-prefectural variation was observed in surgical volume and robotic utilization, and heterogeneity persisted after age- and sex-standardization using SCRs. Urban prefectures exhibited a higher median robotic proportion than rural prefectures (29.3% vs. 19.0%), although this difference did not reach statistical significance (p = 0.09). Treating population density as a continuous measure, robotic proportion was positively associated with population density (Spearman ρ = 0.338, p = 0.020).

CONCLUSIONS: Robotic-assisted rectal resection expanded in Japan after reimbursement, yet marked inter-prefectural heterogeneity remained, underscoring the need for continued nationwide monitoring of geographic variation in adoption.

PMID:42495685 | PMC:PMC13394805 | DOI:10.1002/ags3.70220

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Nevin Manimala Statistics

Diagnostic Accuracy of Size-Based Preoperative CT Assessment for Predicting Lymph Node Metastasis in Colon Cancer: A Systematic Review and Meta-Analysis

Ann Gastroenterol Surg. 2026 Mar 24. doi: 10.1002/ags3.70218. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate identification of preoperative lymph node metastasis is essential for planning colon cancer treatment. Computed tomography (CT) is widely used for staging, but its diagnostic performance based on size criteria alone remains unclear. This study aimed to evaluate the diagnostic accuracy of preoperative CT for detecting lymph node metastasis in colon cancer.

METHODS: A systematic search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was conducted on June 12, 2025. Studies comparing preoperative CT with pathological evaluation and providing 2 × 2 contingency tables were included. Pooled sensitivity and specificity were calculated using a hierarchical summary receiver operating characteristic model and a bivariate random-effects model. Subgroup analyses were performed according to cancer location (colon only vs. colon plus rectal cancer) and diagnostic criteria (size alone vs. size plus morphology). Study quality was assessed using QUADAS-2.

RESULTS: Twenty-nine studies involving 5634 patients were included. The pooled sensitivity and specificity of CT for detecting lymph node metastasis were 0.693 (95% CI: 0.636-0.744) and 0.660 (95% CI: 0.581-0.731), respectively, with an area under the curve of 0.727. Meta-regression showed no statistically significant differences in diagnostic performance between colon-only studies and those including rectal cancer (p = 0.561 and 0.316), or between size-only and morphologic criteria (p = 0.822 and 0.536).

CONCLUSIONS: CT using size criteria alone for preoperative lymph node staging in colon cancer demonstrated only moderate diagnostic performance. These findings indicate that relying on lymph node size as the primary determinant may be insufficient for reliable clinical decision-making.

PMID:42495671 | PMC:PMC13393513 | DOI:10.1002/ags3.70218

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Heterogeneity and plasticity of tumor-associated macrophages in oral squamous cell carcinoma: implications for diagnosis and tumor microenvironment characterization

Front Immunol. 2026 Jul 9;17:1864227. doi: 10.3389/fimmu.2026.1864227. eCollection 2026.

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the predominant histological subtype of oral cavity cancers, with a 5-year survival rate of approximately 50%. The tumour microenvironment, particularly macrophage infiltration and polarization, plays a critical role in tumour progression and patient prognosis. Models describing macrophages as either M1 (pro-inflammatory) or M2 (anti-inflammatory) are increasingly recognized as oversimplified, given the functional heterogeneity and plasticity of tumour-associated macrophages (TAMs). This study aims to evaluate the expression of macrophage markers CD68, CD163, CD11c, and CD115 in OSCC compared to normal oral mucosa (NOM), to assess their diagnostic and prognostic value.

METHODS: A cross-sectional study of 179 tissue samples (111 OSCC, 68 controls) analysed macrophage markers (CD68, CD163, CD11c, CD115) via real-time qPCR. Statistical tests included Mann-Whitney U, ROC analysis for diagnostic utility, Spearman’s ρ for correlations, and assessments of associations with prognosis and recurrence. Cut-offs for gene overexpression were based on ROC results and evaluated clinically.

RESULTS: All four markers showed significantly higher expression in OSCC compared to NOM (p < 0.001 for CD68, CD163, CD11c; p = 0.001 for CD115). ROC analyses demonstrated diagnostic AUCs of 0.69 (CD68), 0.78 (CD163), 0.81 (CD11c), and 0.66 (CD115), indicating poor, fair and good discriminative capacity, respectively. Overexpression of the genes defined by COP was significantly associated with malignancy (p < 0.01). Elevated CD68 and CD163 levels correlated with higher tumour grading (G2/G3), while increased CD11c expression was linked to nodal metastasis (p = 0.04). Strong positive correlations existed between CD115 and the other markers (ρ > 0.61, p < 0.001), supporting a model of macrophage heterogeneity and plasticity. Concurrent upregulation of pro-inflammatory (CD11c) and M2-associated (CD163) markers suggests a complex, dynamic TAM landscape rather than a simple M1/M2 dichotomy.

CONCLUSIONS: Altered RNA expression of the macrophage cell surface markers CD115, CD68, CD163 and CD11c in OSCC, and their respective association with tumour grading, N-status and perineural sheath infiltration, may serve as a basis for future single-cell sequencing or immunohistological – multiplex immunofluorescence – studies. Further investigation of these markers could lead to promising insights into the modulation of the tumour immune microenvironment.

PMID:42495621 | PMC:PMC13391827 | DOI:10.3389/fimmu.2026.1864227

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The toxicity profile and temporal dynamics of dual PD-1/CTLA-4 immune checkpoint blockade: a real-world pharmacovigilance study using the FAERS database

Front Immunol. 2026 Jul 9;17:1868547. doi: 10.3389/fimmu.2026.1868547. eCollection 2026.

ABSTRACT

BACKGROUND: Combination therapy with PD-1 and CTLA-4 inhibitors improves survival in advanced cancers but is associated with heightened toxicity. Whether this represents additive toxicity from each drug or a distinct synergistic profile remains unclear. This study utilized the FDA Adverse Event Reporting System (FAERS) to systematically characterize the toxicity landscape of dual PD-1/CTLA-4 blockade.

METHODS: We analyzed FAERS database (2004-2024) for nivolumab, ipilimumab, and their combination. Disproportionality analysis was performed using Reporting Odds Ratios (RORs) and the Ω shrinkage measure model to detect drug-drug interactions signals. To explore potential synergistic signals, we used two exploratory criteria: 1) Emergent signals: adverse events (AEs) with a significant reporting association only for the combination; 2) Supra-additive reporting signals: combination ROR at least 50% higher than the higher monotherapy ROR.

RESULTS: We identified 15, 252 combination therapy reports. Disproportionality analysis revealed 23 emergent preferred terms (PTs) unique to the combination, including immune-related AEs like cardiotoxicity (ROR = 1.89). Strong supra-additive reporting signals were observed for immune-mediated hepatitis (ROR = 205.80) and endocrine toxicity (ROR = 557.95). The Ω shrinkage measure model detected statistical interaction signals for cytokine release syndrome (Ω=2.35) and immune-mediated dermatitis (Ω=2.48). Among cases with evaluable onset dates, the majority of severe AEs were reported within the first 90 days after treatment initiation, with descriptive differences observed across cancer types. Integrated analysis revealed hepatobiliary disorders were the most frequently reported AEs (28.1% of 675 cases), followed by endocrine disorders (14.2%).

CONCLUSIONS: Our findings are consistent with the hypothesis that dual PD-1/CTLA-4 blockade may be associated with a toxicity profile involving potential supra-additive reporting associations. These signals include emergent safety events not detected with monotherapies, reporting associations in specific organ systems, and observed temporal patterns. These results are hypothesis-generating and await confirmation in independent studies.

PMID:42495618 | PMC:PMC13391816 | DOI:10.3389/fimmu.2026.1868547

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Efficacy and safety of neoadjuvant chemotherapy with immunotherapy versus chemotherapy alone in esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials

Front Immunol. 2026 Jul 9;17:1825905. doi: 10.3389/fimmu.2026.1825905. eCollection 2026.

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive and lethal cancers, with high incidence and mortality rates in East Asia. Neoadjuvant chemotherapy (NC) has traditionally been the standard approach for improving resectability in ESCC, but its limited efficacy in achieving complete pathological responses and enhancing survival has driven interest in combining it with immune checkpoint inhibitors (ICIs), resulting in neoadjuvant chemoimmunotherapy (NIC). Based on randomized controlled trials (RCTs), this meta-analysis compares the risks and clinical benefits of NIC versus NC in resectable ESCC patients.

METHODS: This meta-analysis systematically reviewed data from randomized controlled trials (RCTs) comparing NIC and NC in the treatment of resectable ESCC. Primary outcomes included pathological complete response (pCR) and major pathological response (MPR), while secondary outcomes focused on overall survival (OS), event-free survival(EFS), surgery rate, microscopically margin-negative resection(R0 resection), Intraoperative and hospitalization indicators, T Staging, Response evaluation criteria in solid tumors(RECIST), and adverse events (AEs).

RESULTS: Six high-quality RCTs (1070 patients) were included. NIC significantly improved major pathological response(MPR) (42.8% vs. 22.2%, Odds Ratio(OR) = 2.40, p = 0.0007) and pathological complete response(pCR) (22.2% vs. 8.0%, OR = 3.53, p < 0.00001). NIC was also associated with borderline statistically significant improvements in overall survival (OS) (HR = 0.57, p = 0.05) and R0 resection rate (OR = 2.56, p = 0.05). In addition, NIC enhanced surgical rate (OR = 1.57, p = 0.02), lymph node resection (Mean Difference (MD) = 1.76, P = 0.008), and NIC with a longer interval to surgery (MD = 4.73, p = 0.003, I2 = 95%), although this pooled estimate is less reliable because of considerable heterogeneity. However, immune-related adverse events (iRAEs) were higher in NIC (23.21% vs. 1.16%, p < 0.00001), though severe AEs were similar.

CONCLUSIONS: NIC significantly improves pathological response and other perioperative benefits (e.g., surgical rate and lymph node resection) in resectable ESCC compared with NC, with a trend toward improved survival, despite a higher incidence of irAEs. Further studies are needed to optimize treatment protocols and clarify the long-term impact of immune-related toxicities.

PMID:42495613 | PMC:PMC13391947 | DOI:10.3389/fimmu.2026.1825905

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Comparative assessment of large language models for microbial phenotype assignment

Genome Biol. 2026 Jul 23;27(1):235. doi: 10.1186/s13059-026-04207-7.

ABSTRACT

BACKGROUND: Large language models (LLMs) are increasingly used to extract knowledge from text, yet their coverage and reliability in biology remain unclear. Microbial phenotypes are especially important to assess, as comprehensive data remain sparse except for well-studied organisms and they underpin our understanding of microbial characteristics, functional roles, and applications.

RESULTS: Here, we systematically assessed the biological knowledge encoded in publicly available LLMs for structured phenotype assignment of microbial species. We evaluated the performance of up to 57 LLMs across different experiments, including state-of-the-art models such as Claude Sonnet 4 and the GPT-5 family of models. Across phenotypes, LLMs reached accurate assignments for many species, but performance varied widely by model and trait, and no single model dominated. Model self-reported confidence is informative, with higher confidence aligning with higher accuracy, and can be used to prioritize phenotype assignment, effectively distinguishing between high- and low-confidence inferences.

CONCLUSIONS: Overall, our study outlines the utility and limitations of text-based LLMs for phenotype characterization in microbiology.

PMID:42493805 | DOI:10.1186/s13059-026-04207-7

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Nevin Manimala Statistics

The Metaproteomics Initiative: five years of community-driven progress

Microbiome. 2026 Jul 23;14(1):186. doi: 10.1186/s40168-026-02463-0.

ABSTRACT

The Metaproteomics Initiative was officially launched in 2021 to strengthen collaboration, promote knowledge exchange, and support and lead standardization efforts within the growing metaproteomics community. Over the past 5 years, the Initiative has developed into a structured, global network of researchers. It has launched community-driven benchmark studies, helped shape emerging metadata and reporting standards, developed practical guidance and training materials, organized international symposia, and fostered connections across the microbiome research landscape ( https://metaproteomics.org/ ). We outline the Initiative’s organization, activities, achievements, and ongoing efforts, and reflect on how sustained, community-led coordination has shaped the development of metaproteomics as a field. We further position the Grand Metaproteome Challenges as a next step toward coordinated, community-scale biological research, aimed at advancing functional microbiome studies across clinical, industrial, and environmental application domains, and invite engagement from the wider microbiome and omics communities. Video Abstract.

PMID:42493801 | DOI:10.1186/s40168-026-02463-0

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The need for standardization and improved open (meta)data practices in metaproteomics

Microbiome. 2026 Jul 23;14(1):185. doi: 10.1186/s40168-026-02455-0.

ABSTRACT

Metaproteomics enables functional insight into microbial communities by identifying and quantifying proteins in complex samples. Yet, heterogeneous analytical workflows and the lack of standardization across experimental and bioinformatics stages hinder reproducibility and comparability, limiting integration with other omics data. We here present a community-developed reporting checklist tailored to the specific needs of metaproteomics. We also outline current efforts to enable structured and interoperable metadata capture, drawing on standards from proteomics and microbiome research wherever possible. By promoting transparent reporting and advancing metadata practices, our recommendations aim to align metaproteomics more closely with FAIR principles and support reproducible and interoperable research practices. Video Abstract.

PMID:42493800 | DOI:10.1186/s40168-026-02455-0

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Intravenous placenta-derived mesenchymal stem cells enhance early survival as an adjunct to supportive care in severe burn: a preclinical study

Stem Cell Res Ther. 2026 Jul 24;17(1):259. doi: 10.1186/s13287-026-05053-x.

ABSTRACT

BACKGROUND: Severe burn injury induces a rapid systemic inflammatory response, and early survival depends heavily on timely fluid resuscitation and thermal support. However, optimal supportive care may be difficult to deliver in austere or resource-limited environments. Placenta-derived choriodecidual mesenchymal stem cells (pcMSCs) possess immunomodulatory properties and may improve outcomes when supportive care is suboptimal. This study investigated whether intravenous pcMSC therapy improves early survival after severe burn injury in a preclinical model.

METHODS: Sixty adult male Sprague-Dawley rats underwent standardized 40% total body surface area full-thickness burns and were randomly assigned to six groups (n = 10/group) differing in fluid resuscitation (1× vs. 3× Ringer’s lactate), thermal support (heating lamp vs. incubator warming), and intravenous pcMSC therapy. Survival was monitored for 14 days and analyzed using Kaplan-Meier methods with log-rank testing. Serum TNF-α, IL-1β, and IL-6 levels, body weight, water intake, and core body temperature were assessed longitudinally in selected groups.

RESULTS: Survival differed significantly among groups, with 93% of deaths occurring within the first 3 days post-burn. Under low-volume resuscitation, survival declined to 30% in untreated animals and improved to 50% with pcMSC therapy, indicating a survival benefit under insufficient resuscitation conditions. With adequate fluid resuscitation and thermal support, survival was high without pcMSCs (80%) and numerically higher with pcMSCs (90%), although this difference was not statistically significant after adjustment. Thermal support exerted a marked effect on outcomes, with warmed animals demonstrating substantially higher survival despite similar or lower fluid volumes. PcMSC treatment attenuated post-burn hypothermia, reduced weight loss and dehydration, and significantly decreased circulating TNF-α, IL-1β, and IL-6 levels.

CONCLUSIONS: Placenta-derived choriodecidual mesenchymal stem cells may confer an additive survival benefit after severe burn injury, particularly under inadequate fluid resuscitation and thermal support, likely through stabilization of body temperature, improved hydration, and attenuation of systemic inflammation, supporting their potential role as an adjunctive therapy in austere or resource-limited settings.

PMID:42493791 | DOI:10.1186/s13287-026-05053-x