Nevin Manimala

World J Gastroenterol. 2026 Mar 7;32(9):114200. doi: 10.3748/wjg.v32.i9.114200.

ABSTRACT

BACKGROUND: Assessment of the prognosis, follow-up monitoring, and adjuvant treatment decision-making for patients with stage II and III colorectal cancer (CRC) are controversial, as CRC harbors tremendous heterogeneity. Carcinoembryonic antigen (CEA) is an important tumor marker; however, the use of this marker in the management of CRC has not garnered adequate attention.

AIM: To determine the significance of perioperative CEA levels in prognostic stratification and treatment decision making to provide personalized diagnosis and treatment for patients with stage II and III CRC.

METHODS: Patients in the training and validation cohorts were diagnosed with primary stage II or III CRC. Preoperative CEA (pre-CEA) and postoperative CEA (post-CEA) were collectively defined as perioperative CEA. Kaplan-Meier (K-M) survival analyses were used to describe patient survival. Cox stepwise regression analysis based on Akaike information criterion was used to determine the prognostic value of clinicopathological characteristics. Nomograms were developed to predict the probability of overall survival (OS) and disease-free survival (DFS). Annual hazard curves and pie charts were used to demonstrate the features of recurrence or metastasis. Differences were considered statistically significant at P < 0.05.

RESULTS: A total of 2496 and 1293 patients were included in the training and validation cohorts, respectively. K-M analysis indicated that patients with elevated perioperative CEA had poorer OS and DFS, with post-CEA being an independent prognostic factor for OS and DFS. Nomograms based on factors associated with prognosis were constructed, which showed good predictive ability for 3-, 5-, and 7-year OS and DFS. Patients with elevated perioperative CEA were more likely to have recurrence or metastasis, and the period of the second year after surgery was the peak time of recurrence or metastasis. OS and DFS were significantly worse in patients without adjuvant chemotherapy when they had elevated perioperative CEA. Adjuvant chemotherapy could significantly improve the OS of patients with elevated perioperative CEA. Patients with elevated post-CEA who received XELOX could achieve better OS and DFS.

CONCLUSION: Perioperative CEA demonstrate sufficient sensitivity in the prognosis prediction and follow-up of patients with stage II and III CRC. Furthermore, perioperative CEA, especially post-CEA, show promise in guiding adjuvant chemotherapy, suggesting potential for further study.

PMID:41810442 | PMC:PMC12968575 | DOI:10.3748/wjg.v32.i9.114200

Curr Res Food Sci. 2026 Mar 2;12:101371. doi: 10.1016/j.crfs.2026.101371. eCollection 2026.

ABSTRACT

The brewing process is a crucial step in determining the flavor profile of green tea infusions. However, the flavor differences arising from top-brewing and bottom-brewing methods remain poorly understood, and the underlying mechanisms are largely unexplored. In this study, GC-MS and sensory analysis were employed to investigate the flavor differences in Shucheng Little Cymbidium tea infusions under varying water temperatures and brewing methods. Subsequently, the variations in major polyphenolic compounds were analyzed, and the potential causes of flavor differences were explained from the perspective of the interactions between EGCG and key aroma compounds. Multivariate statistical analysis revealed that compounds such as geraniol, nonanal, and methyl salicylate serve as important markers for discriminating between different brewing conditions. Moreover, EGCG exhibited a significant binding effect with compounds such as geraniol and nonanal, driven by hydrogen bonding and hydrophobic interactions. This binding may regulate the transfer of aroma compounds from tea leaves to the infusion during brewing, thereby shaping distinct sensory characteristics. These findings provide a molecular-level rationale for empirical techniques in traditional tea art. More importantly, it inspires researchers to pay attention to the crucial role of the tea infusion matrix in determining flavor.

PMID:41810421 | PMC:PMC12969635 | DOI:10.1016/j.crfs.2026.101371

Trauma Surg Acute Care Open. 2026 Mar 6;11(1):e001924. doi: 10.1136/tsaco-2025-001924. eCollection 2026.

ABSTRACT

INTRODUCTION: Globally, trauma patients suffer from high rates of preventable deaths, in part driven by low rates of access to and application of resource-relevant evidence-informed clinical guidance. This mixed-methods study assessed the accessibility (barriers to attempting to use guidance), clarity (ease of comprehension), utility (based on resources and time), and implementation of trauma guidance for Peruvian injury providers.

METHODS: Semistructured qualitative interviews were conducted in Spanish at three hospitals in Lima, Peru. Interviews were analyzed in Dedoose V.9.1.12 using an iteratively developed codebook; quantitative self-administered surveys were then developed and distributed at the Pan American Trauma Society Conference. Surveys were analyzed using descriptive statistics and frequencies.

RESULTS: 38 interviews and 83 surveys were conducted with surgical attendings, emergency physicians, and surgical and emergency residents across all years of training. Access barriers included paywalls, language barriers, low user-friendliness, and technology limits (poor internet, few computers). A mobile app and portable physical guidance are preferred potential solutions. Utility barriers included low equipment maintenance and high patient volumes. Resource-based guidance, conciseness (eg, flowcharts), and standardization are perceived to potentially increase utility. Implementation barriers included limited training time, reliance on more experienced colleagues rather than guidance, low enforcement, and low funding. Potential facilitators are increased administrative support and staff willingness to use guidance improving patient mortality, clinical errors, and length of stay. No barriers to clarity were reported.

CONCLUSION: Barriers to using clinical guidance included low user-friendliness, low local applicability, and an unsupportive culture. Mobile apps, resource stratification, and administrative involvement are priorities to address these needs. Trauma guidance adapted to local realities may reduce preventable deaths in acute care. Further work is needed to identify how to create and distribute updated clinical guidance to better serve trauma providers worldwide.

LEVEL OF EVIDENCE: Economic and Value-based Evaluations Level 2.

PMID:41810415 | PMC:PMC12970114 | DOI:10.1136/tsaco-2025-001924

Front Vet Sci. 2026 Feb 23;13:1751034. doi: 10.3389/fvets.2026.1751034. eCollection 2026.

ABSTRACT

INTRODUCTION: Endothelial glycocalyx damage contributes to morbidity and mortality in critical illness. In this exploratory study in cats with trauma and non-traumatic illness, the endothelial glycocalyx thickness was estimated using sidestream dark field videomicroscopy and the Glycocheck™ software, with the primary aims of assessing feasibility, describing of Glycocheck™ microcirculatory parameters and exploring potential effects of illness severity and IV fluid administration.

METHODS: This was a prospective, single center, observational study. Recorded variables included age, weight, diagnosis, length of hospitalization (LOH), packed cell volume (PCV) and IV fluid administration. Each patient was assigned a fast Acute Patient Physiologic and Laboratory Evaluation score (APPLE_fast) and for cats with trauma – Animal Trauma Triage score (ATT). Within 24 h from admission, cats were anesthetized, and images from the sublingual mucosal vessels obtained for Glycocheck™ analysis. The perfused boundary region (PBR), an inverse estimate for endothelial glycocalyx thickness, was calculated for vessels with diameter of 5-25, 5-9, 10-19 and 20-25 μm, respectively. Normality was assessed using Shapiro-Wilk test and histograms. The effects of APPLE_fast, LOH, ATT, PCV, IV fluid administration, and illness group on PBR were analysed using generalised linear models. Distribution of vascular segment counts was assessed using Friedman’s test and Wilcoxon rank-signed test.

RESULTS: Nineteen cats were included, 11 with trauma. Success rate for measurements was 95%. Survival to discharge was 95%. Mean ± standard deviation for PBR 5-25 was 2.60 ± 0.22 μm, PBR 5-9: 1.38 ± 0.15 μm, PBR 10-19: 3.02 ± 0.22 μm and PBR 20-25: 3.03 ± 0.38 μm, within previously established tolerance intervals. There were no statistically significant effects of group, LOH, ATT, APPLE_fast, PCV and IV fluids on any PBR measurements. Vascular segment counts across the 5-25 μm range were not equally distributed (p < 0.001).

CONCLUSION: This exploratory study demonstrates the feasibility of assessing endothelial glycocalyx thickness in hospitalized sick cats. While no effects of clinical variables on PBR were identified, the study highlights important methodological considerations and provides valuable insights to guide future, larger-scale investigations.

PMID:41810410 | PMC:PMC12967996 | DOI:10.3389/fvets.2026.1751034

Gastro Hep Adv. 2025 Oct 12;5(4):100835. doi: 10.1016/j.gastha.2025.100835. eCollection 2026.

ABSTRACT

BACKGROUND AND AIMS: Crohn’s disease (CD) patients may experience anastomotic bleeding after lower gastrointestinal surgery, but its endoscopic management remains underexplored. We aimed to analyze the risk factors for anastomotic bleeding and the efficacy of endoscopic treatment.

METHODS: We retrospectively analyzed clinical characteristics, endoscopic treatments, and outcomes of CD patients with postoperative anastomotic bleeding from January 2021 to May 2025 at multiple centers. Anastomotic bleeding was defined as (i) direct bleeding (melena/hematochezia) or (ii) hemoglobin decrease ≥2 g/dL. Patients were followed up for 1 year, with rebleeding requiring endoscopic reintervention.

RESULTS: We included a total of 21 patients with 100% of patients having onsite bleeding controlled with initial endoscopic treatment and 9 patients (42.9%) having rebleeding. There was no statistical difference between the rebleeding group and nonrebleeding group in terms of age, gender, comorbidity, anticoagulation or antiplatelet therapy, clotting disorder, hemoglobin before or after procedure, bleeding type, the Rutgeert’s score, and endoscopic treatment. However, a greater number of patients in the rebleeding group required blood transfusion (88.9% vs 33.3%, P value = .011), and a greater volume of blood transfusion 2.0 (2.0-3.5 units) vs 0.0 (0.0-1.8 units) than those in nonrebleeding group (P value = .013). None of the 21 patients had no endoscopy-associated complications.

CONCLUSION: Endoscopic therapy appears to be safe and effective for the majority of CD patients with anastomotic bleeding following bowel surgery. The requirement for blood transfusion at the inception, in conjunction with a high volume of blood transfusion appear to be high risk factors for rebleeding.

PMID:41810383 | PMC:PMC12969671 | DOI:10.1016/j.gastha.2025.100835

medRxiv [Preprint]. 2026 Feb 24:2026.02.23.26346831. doi: 10.64898/2026.02.23.26346831.

ABSTRACT

The daily cortisol cycle is a critical indicator of hypothalamic-pituitary-adrenal (HPA) axis function. The current analytical approaches produce several outputs difficult to integrate into simple statistical models, clinical workflows, and ML/AI pipelines requiring single-value inputs. We developed the Cortisol Sine Score (CSS), a model-free scalar metric that quantifies daily cortisol exposure by computing a weighted sum of cortisol measurements across the day, using sine-transformed time-of-day weights. The CSS produces positive values for morning-dominant patterns, negative values for evening-shifted profiles, and near-zero values for flattened rhythms characteristic of chronic stress and circadian disruption. We validated the CSS performance in 3,006 samples from 501 pregnant women enrolled in the March of Dimes program, with cortisol values measured at 6 time points per day collected during the second trimester of pregnancy. The CSS showed strong correlations with observed and model-estimated amplitude and acrophase from Cosinor regression and JTK_CYCLE approaches, with excellent classifying performance (AUC=0.89, high versus low). The CSS successfully captured established associations between social disadvantage and cortisol dysregulation, and demonstrated utility in predicting gut microbiome composition in metagenomic analyses. Importantly, the CSS maintains excellent fidelity to the full 6-sample protocol with as few as 3-4 daily measurements. The 4-sample protocol achieves great performance (r = 0.952, MAE = 0.087) while reducing participant burden. The 06:00 time point was identified as essential for accurate CSS quantification. The CSS bridges the gap between circadian analysis and practical implementation by providing a simple, interpretable, and robust assessment of cortisol daily cycle in large-scale epidemiological studies, clinical screening, and biomedical sensors.

HIGHLIGHTS: Current state-of-the-art approaches estimating the daily cortisol exposures produce multi-output information difficult to implement in simple statistical analyses or ML/AI multi-omics approachesCortisol Sine Score is a novel model-free scalar metric expressing cortisol daily exposure and rhythmicity (morning vs evening exposure)Cortisol Sine Score was validated using 3006 salivary samples from clinical data and golden standards in circadian analyses such as Cosinor and JTK_CYCLECortisol Sine Score was the top performer in our benchmarking approach predicting association with social disadvantage and gut microbiome compositionReliable with 3-4 daily samples, reducing participant burdenOpen-source R package CortSineScore democratizes cortisol cycle analysis.

PMID:41810379 | PMC:PMC12970380 | DOI:10.64898/2026.02.23.26346831

medRxiv [Preprint]. 2026 Feb 28:2026.02.23.26346364. doi: 10.64898/2026.02.23.26346364.

ABSTRACT

Cohesin is a fundamental genome-organizing complex that orchestrates three-dimensional chromosome folding and gene expression via DNA loop extrusion. Alterations to genes encoding cohesin subunits and cohesin loaders cause Mendelian disorders, including Cornelia de Lange syndrome (CdLS). By contrast, disruption of factors that remove cohesin from DNA, including WAPL and its binding partners PDS5A and PDS5B , have not yet been associated with human disease. Here, we explored the relevance of these cohesin release factors in Mendelian disease by establishing a rare disease cohort of deeply phenotyped individuals with heterozygous, predicted damaging variants in WAPL (n=27), PDS5A (n=8), and PDS5B (n=8), by modeling WAPL deficiency in human cell lines and mice, and by aggregating rare disease association statistics from consortia studies. We identified a WAPL -related disorder characterized by developmental delay, intellectual disability, and risk of other developmental anomalies including clubfoot. Similarities between individuals with damaging WAPL variants and those with large, recurrent 10q22.3q23.2 (10q) deletions (which encompass WAPL ) nominate WAPL as a driver gene within this genomic disorder region. While carriers of PDS5A or PDS5B variants exhibited features of developmental disorders, neither cohort-based statistics nor case phenotyping associated these genes with specific phenotypes. We used CRISPR engineering to generate truncating variants in WAPL , as well the 7.8 Mb 10q deletion or duplication in human iPSCs and induced neurons. Transcriptomic analyses identified differentially expressed genes in both models, with highly significant overlap between WAPL haploinsufficiency and 10q deletion signatures. Mice with 50% residual Wapl expression exhibited mild deficits of growth and learning/memory, whereas those with 25% residual Wapl expression displayed birth defects and postnatal lethality, revealing a dosage liability threshold below the level of heterozygosity. In summary, we delineated a novel genetic condition caused by cohesin release factor deficiency, nominated WAPL as a driver gene within a genomic disorder region, and further illuminated dosage sensitivity of human cohesin.

PMID:41810376 | PMC:PMC12970359 | DOI:10.64898/2026.02.23.26346364

medRxiv [Preprint]. 2026 Feb 25:2026.02.23.26346922. doi: 10.64898/2026.02.23.26346922.

ABSTRACT

Genome-wide association studies (GWAS) have implicated tens of thousands of genetic variants associated with complex traits and polygenic diseases. Colocalizing GWAS variants with variants that may regulate gene expression, via expression quantitative trait loci (eQTL) mapping, has successfully led to the identification of disease-critical genes and their cell types of action. Recent studies predominantly colocalize proximal cis -eQTLs, which are estimated to regulate ∼10% of variance in gene expression levels. However, trans -eQTLs have been hypothesized to account for an additional ∼20% of expression levels, although few studies have attempted to quantify the variance explained by empirically associated trans -eQTLs. Here, we introduce EGRET (Estimating Genome-wide Regulatory Effects on the Transcriptome), an ensemble framework that jointly models cis -eQTLs with three distinct trans -eQTL mapping approaches: standard pairwise association testing via Matrix eQTL, and two functionally-informed methods, trans-PCO and GBAT. In real data, EGRET produced 353,408 predictive gene expression models (cross-validation R ² > 0, p < 0.01) across 49 GTEx tissues, including 12,317 gene-tissue pairs with a significantly nonzero trans -heritable component. For this set of genes, EGRET models explain 33% more gene expression variance than cis -eQTL models (EGRET average R ² = 0.104, FUSION average R ² = 0.078). We found that putative trans-regulating variants of EGRET models are enriched for regulatory elements such as enhancers, histone marks, and cis -eQTLs of other genes. We then hypothesized that EGRET models could nominate new disease-critical genes via a transcriptome-wide association study (TWAS) framework that models genome-wide regulatory effects on gene expression. In simulations of theoretically representative gene expression architectures (∼30% heritability, where more than 70% is distal), EGRET increased the power to detect disease-critical genes by 1.2x-3.1x compared to cis -eQTL models. In real data analysis, we identified disease-associated genes via TWAS across GWAS summary statistics for 78 complex traits and polygenic diseases using gene expression prediction models from EGRET, cis -eQTL FUSION, and two state-of-the-art trans -eQTL TWAS methods, MOSTWAS and BGW-TWAS. EGRET identified 450,825 gene-disease associations that were not identified by FUSION models, 2,900 associations not identified by MOSTWAS, and 5,498 associations not identified by BGW-TWAS. Finally, we used EGRET models to construct gene regulatory networks, some of which harbored genes that were jointly associated with complex traits. For example, the gene members of the network defined by ARHGEF3 , whose cis -regulatory variants help predict expression of 10 genes in trans , were concordantly associated with platelet count using EGRET but not FUSION models. Overall, we find that modeling the genome-wide genetic component of gene expression greatly boosts the detection of disease-critical genes and helps define gene regulatory networks while improving the characterization of GWAS variants.

PMID:41810371 | PMC:PMC12970377 | DOI:10.64898/2026.02.23.26346922

medRxiv [Preprint]. 2026 Feb 27:2026.02.25.26347015. doi: 10.64898/2026.02.25.26347015.

ABSTRACT

Polygenic scores (PGS) have emerged as an important tool for genetic risk prediction in medicine to identify individuals at high-risk for disease. A major limitation in their implementation is the apparent disagreement among scores for the same individual decreasing their interpretability and utility in clinical settings. Here we show that the poor agreement across PGSes for type 2 diabetes (T2D) is fully explained by statistical uncertainty in PGS-based prediction; individual-level uncertainty estimates from a single PGS explain the variability across existing PGSes. We provide an approach for the selection of high-risk individuals that incorporates measures of uncertainty and show that individuals with high confidence based on their PGS uncertainty have higher risk agreement across existing PGS and are more likely to develop T2D than high-risk individuals based on only point estimates of PGS. Together, these findings shed light on the factors underlying a roadblock in PGS implementation and underscore the need to incorporate uncertainty in PGS-based predictions.

PMID:41810369 | PMC:PMC12970363 | DOI:10.64898/2026.02.25.26347015

Risk Manag Healthc Policy. 2026 Mar 4;19:572604. doi: 10.2147/RMHP.S572604. eCollection 2026.

ABSTRACT

PURPOSE: Climate extremes are a catastrophic manifestation of climate change. Motorcycle ambulances are an emerging sort of vehicle that is intended to offer quick access in large cities. This study evaluated the effect of extreme weather events on the accessibility of emergency motorcycle ambulance services.

PATIENTS AND METHODS: We conducted a retrospective analysis of motorcycle ambulance operation data from January 2020 to December 2024. Data on motorcycle ambulance operating times, rainfall levels in the operational area, and ground temperatures at the Emergency medical services (EMS) unit were collected. Continuous data were presented as means and standard deviations (SD), while categorical data were reported as frequencies and percentages. Associations between categorical variables were evaluated using the chi-square test. A two-tailed p-value of less than 0.05 was considered statistically significant.

RESULTS: With a total of 569 operations documented over the five years, services were postponed during rainy weather and when ground temperatures exceeded 40°C. The availability of operational motorcycle ambulances declined from 81.28% to 34.03%. Increased rainfall (hours lost increased from 1065.1 to 2711.7; p<0.001) and rising temperatures exceeding 40°C (hours lost increased from 574.9 to 3067.3; p<0.001) were the main causes of service interruptions. This occurred despite increased utilization of motorcycle ambulances for emergency responses (65 to 165 operations annually; p=0.022) and a growing use of AED-equipped units for cardiac emergencies (4.6% to 23.6% of operations; p=0.014).

CONCLUSION: This quantitative evidence of the impact of climate extremes on emergency healthcare access due to reduced motorcycle ambulance availability. The gradual reduction in operational hours was caused by rising rainfall and elevated temperatures.

PMID:41810354 | PMC:PMC12968811 | DOI:10.2147/RMHP.S572604