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  • True Positives
  • True Positives

Articles published on Positive Proportion

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  • New
  • Research Article
  • 10.1016/j.ijid.2025.108356
Genotypic characterization and epidemiology of genital Chlamydia trachomatis among women: A hospital-based study in Hangzhou, China.
  • Mar 1, 2026
  • International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
  • Qingxue Zhou + 5 more

Genotypic characterization and epidemiology of genital Chlamydia trachomatis among women: A hospital-based study in Hangzhou, China.

  • New
  • Research Article
  • 10.3390/microorganisms14030556
Response of Soil Microbial Communities to Karst Desertification in Soil and Water Conservation Agroforestry Systems
  • Feb 28, 2026
  • Microorganisms
  • Wanmei Hu + 6 more

Karst desertification (KD) severely constrains regional ecological security and sustainable development. As an important ecological restoration measure, soil and water conservation agroforestry (SWCAF) systems have unclear mechanisms for soil microbial responses. This study investigated the effects of potential–light (PL), light–moderate (LM), and moderate–high (MH) KD on soil physicochemical properties and microbial communities in Karst SWCAF (KSWCAF) systems. It explored the drivers of microbial community changes. The results showed that (1) Soil physicochemical properties exhibited nonlinear changes along the KD gradient. Key soil-fertility indicators including silt, clay, total porosity (TP), total phosphorus (Total_P), total nitrogen (Total_N), soil organic carbon (SOC), and carbon nitrogen ratio (C_N) showed significant unimodal patterns, peaking at the LM stage with optimal overall soil quality; (2) The dominant bacterial phyla were Pseudomonadota, Acidobacteriota, Actinomycetota, and Planctomycetota, while the dominant fungal phyla were Ascomycota, Basidiomycota, and Mortierellomycota. The overall abundance of these dominant phyla increased with intensifying KD, except that the relative abundance of Pseudomonadota was lowest in the QZ study area, while Acidobacteriota was highest in the QZ area. The dominant fungal phylum Ascomycota increased with KD intensification; (3) KD significantly influenced microbial community structure and beta diversity. Fungi showed stronger responses to the KD gradient than bacteria. Bacterial alpha diversity was significantly higher in the LM stage compared to the PL and MH stages (p < 0.05), while fungal alpha diversity was significantly lowest in the MH stage (p < 0.05); (4) Bacterial networks exhibited highest complexity but reduced stability at the LM stage, whereas fungal networks enhanced stability at the MH stage by increasing modularization and positive correlation proportions; (5) RDA revealed that soil physicochemical factors explained 66.89% and 98.82% of bacterial and fungal community variation, respectively, with pH, moisture, and C_N as key drivers. Overall, KD regulates microbial community structure and functional allocation by reshaping the soil environmental gradient, with the LM stage potentially representing a “transitional optimization window” for KSWCAF ecosystem structure and function. This study provides a theoretical basis for microbial regulation strategies in KD control and soil and water conservation (SWC) processes.

  • New
  • Research Article
  • 10.17587/it.32.104-112
Modifications of the method for predicting sharp activity surges in systems with network effects using adaptive parameters
  • Feb 18, 2026
  • Informacionnye Tehnologii
  • V V Ryabov + 2 more

The article proposes modifications to the method for predicting abrupt changes in activity in software products with network effects, aimed at improving the accuracy and timeliness of detecting critical events. The focus is on adaptive parameters of the method, including a dynamic activation threshold for predictive signals dependent on current data volatility and automatic determination of the moving average window width based on local variability of activity metrics. А comparative analysis of the effectiveness of each modification was conducted using performance metrics defined in the article and visualization of results. It was found that the adaptive threshold reduces the proportion of false positives, while the algorithm for automatically selecting the moving average window width enables earlier detection of predictive signals. The results demonstrate that combining the proposed modifications ensures a balance between sensitivity and reliability of predictions, which is particularly important for social network monitoring systems and forecasting the risk of coordinated destructive actions by users.

  • New
  • Research Article
  • 10.1158/1557-3265.sabcs25-ps3-12-27
Abstract PS3-12-27: Comparative analysis of the tumor immune microenvironment (TIME) and primary and metastatic tissue in HR+/HER2- and triple-negative breast cancer (TNBC)
  • Feb 17, 2026
  • Clinical Cancer Research
  • A Levee + 8 more

Abstract Background: Immune checkpoint inhibitor (ICI) based regimens are standard of care for patients with TNBC and clinical trials are investigating ICI in HR+/HER2- breast cancer, with encouraging results in a subset of patients. The tumor immune microenvironment (TIME) plays a critical role in ICI response and can differ significantly by metastatic site. Given the expanding integration of ICIs in HR+/HER2- breast cancer trials, we examined the TIME across sites of disease and subtypes to illustrate how these anatomical sites are molecularly different and may impact ICI benefit. Methods: We used Tempus Lens (Tempus AI, Inc., Chicago, IL) to retrospectively analyze de-identified next-generation sequencing data from patients with HR+/HER2- breast cancer (n=6,818) and TNBC (n=2,715) in the Tempus Database. Metaplastic histology was excluded. Among HR+/HER2- breast cancer and TNBC, tumors from primary breast (PB, n=4451), liver (n=1117), bone (n=845), lymph node (LN, n=425), lung (n=388), and brain/CNS (n=234) metastatic sites were sequenced with Tempus xT DNA (648-gene panel) and xR RNA assays. TMB, MSI, PD-L1 (CPS, clone 22c3), and proportions of B, T (CD4+, CD8+), NK cells, and macrophages of immune cells via quanTIseq deconvolution were compared across metastatic sites in HR+/HER2- breast cancer and compared to TNBC. Chi-squared/Fisher’s exact or Kruskal-Wallis tests were used to assess statistical significance. Results: In this study, the median age at diagnosis in the HR+/HER2- and TNBC cohort was 58 and 57, respectively and both cohorts were diverse: White (50%/44%), African American (8%/14%), Hispanic (6.7%/7%), Asian (3.1%/2.3%), other race (5.5%/5.5%) and unknown (33%/34%). Overall, 67% of patients were stage IV. Among patients with HR+/HER2- breast cancer, brain/CNS (14%) was most commonly TMB high (≥10 mut/mB) followed by bone (9.4%) and liver (8.9%) (p<0.001). PD-L1 >=10% (positive) proportions were highest in PB (4.1%), lung (3.6%) and LN (4.9%) (p<0.001). LN had the highest proportions of B cells and T cells (CD4+ and CD8+) and the lowest proportion of macrophages (M1 and M2) and NK cells (p<0.001). Besides LN, CD8+ T cells were in higher proportions in lung and PB compared to liver, bone, and brain/CNS metastases (p<0.001). In TNBC, PB, lung, and LN metastases had the highest proportions of PD-L1 positive status as well as CD8+ T cell proportions compared to liver, bone, and brain/CNS (both, p<0.001). Compared to TNBC, HR+/HER2- breast cancer had different proportions for all immune cell populations in PB and all non-breast sites (exception NK cells, all else p<0.05). Notably, HR+/HER2- breast cancer had lower proportions of CD8+ T cells and M1 macrophages and higher proportions of M2 macrophages across PB and all non-breast sites compared to TNBC (all, p<0.001). Liver metastases had the highest proportions of M1 macrophages, NK cells, and neutrophils compared to all other sites in HR+/HER2- breast cancer, with a similar pattern seen in TNBC (all, p<0.001). Conclusions: In HR+/HER2- and TNBC, the TIME significantly differed according to site of disease. Although more commonly TMB high, liver, bone, and brain/CNS metastases were composed of lower proportions of CD8+ T cells in HR+/HER2- breast cancer. HR+/HER2- breast cancer was less immunogenic across all disease sites compared to TNBC. However, patients with breast, lung, and LN metastases had the highest proportions of CD8+ T cells in both subtypes, indicating a subset of patients with HR+/HER2- breast cancer that could be enriched for ICI response. These analyses may support TIME biomarkers for patient selection in ICI focused clinical trials for patients with breast cancer. Citation Format: A. LeVee, J. Bitar, E. B. Jaeger, U. Jariwala, J. Mercer, C. Egelston, H. McArthur, Y. Yuan, I. Kang. Comparative analysis of the tumor immune microenvironment (TIME) and primary and metastatic tissue in HR+/HER2- and triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-12-27.

  • Research Article
  • 10.36721/pjps.2026.39.4.reg.15348.1
Clinical outcomes and Th17-associated immunomodulation in vitiligo treated with tacrolimus ointment plus narrow-band ultraviolet light.
  • Feb 8, 2026
  • Pakistan journal of pharmaceutical sciences

Vitiligo, an autoimmune disorder causing skin depigmentation, has Narrow-Band Ultraviolet B (NB-UVB) and tacrolimus with limitations, warranting further research on the long-term efficacy, safety and T helper cell (Th) 17-related mechanisms of their combination. This study assessed the Th17-related immunomodulation, efficacy and tolerability of tacrolimus plus NB-UVB in vitiligo. Retrospectively collected 132 vitiligo patients from our hospital (Jan 2020-Dec 2023); 124 were enrolled after excluding. Patients were divided into tacrolimus combined with NB-UVB group (n=63) and tacrolimus group (n=61). Primary outcomes Vitiligo Area Scoring Index (VASI) scores and clinical efficacy. Secondary outcomes Th17 cell proportion, serum Interleukin (IL)-17/IL-22 levels, Rretinoic Acid Receptor-Related Orphan Receptor γt (RORγt)-positive cell proportion, Dermatology Life Quality Index (DLQI) scores, Hospital Anxiety and Depression Scale (HADS) scores and adverse event incidence. The combination group showed a greater reduction in VASI scores (P=0.041) and a higher effective rate (P=0.010) compared with the tacrolimus-group alone. The combination group had a significantly lower Th17 cell proportion (P=0.003), IL-17 levels (P<0.001), IL-22 levels (P=0.047), RORγt-positive cell proportion (P=0.029). Adverse event incidence was not different between groups (P=0.714), while the combination group had a lower DLQI (P<0.001), HADS-A (P=0.018) and HADS-D (P=0.006) scores. Tacrolimus plus NB-UVB is more effective than tacrolimus alone for vitiligo, reducing lesion size and disease activity, down regulating Th17-associated immunity and improving systemic immune profile.

  • Research Article
  • 10.1016/j.mcpro.2026.101534
Exploring an Intermediate Colorectal Cancer Screening Test Based on Stool Proteomics and Machine Learning for Optimizing the Selection of Patients for Colonoscopy Identified from FIT.
  • Feb 1, 2026
  • Molecular & cellular proteomics : MCP
  • David Gagné + 9 more

Exploring an Intermediate Colorectal Cancer Screening Test Based on Stool Proteomics and Machine Learning for Optimizing the Selection of Patients for Colonoscopy Identified from FIT.

  • Research Article
  • 10.1371/journal.pdig.0000739
From patient voices to policy: Data analytics reveals patterns in Ontario's hospital feedback.
  • Feb 1, 2026
  • PLOS digital health
  • Pourya Momtaz + 8 more

Patient satisfaction is a central measure of high-performing healthcare systems, yet real-world evaluations at scale remain challenging. In this study, we analyzed 122,194 de-identified patient reviews from 45 Ontario general hospitals between January 2015 and July 2022. We applied a natural language processing (NLP) pipeline using a clinical named entity recognition (NER) model fine-tuned on biomedical literature to extract references to diseases, symptoms, and medical procedures from patient reviews. Geospatial analysis was conducted to examine sentiment patterns based on regional census data related to low-income status and visible-minority composition. Our primary objective was to investigate how the COVID-19 pandemic influenced patient satisfaction trends, with a specific focus on clinical units and hospitals serving marginalized populations. We assessed changes in the proportion of positive comments across time periods and socioeconomic groups using multivariate logistic regression. Our findings show that over 80% of the hospitals studied had fewer than 50% positive reviews, highlighting possible systemic gaps in patient needs. Interestingly, the proportion of negative reviews decreased during the COVID-19 pandemic, suggesting possible changes in patient expectations or increased appreciation for healthcare workers. However, certain units, such as dentistry and radiology, experienced more negative ratings as a proportion of their total reviews. 'Anxiety' emerged as a recurrent concern in negative reviews, especially during the start of the pandemic, pointing to the growing awareness of mental health needs. Based on our geospatial analysis, hospitals located in regions with higher percentages of visible minority and low-income populations initially saw higher positive review proportions before COVID-19, but this trend reversed after 2020. Our statistical models confirmed that these shifts were significant, particularly for low-income-serving hospitals. Collectively, these results demonstrate how large-scale unstructured data can identify fundamental drivers of patient satisfaction, while underscoring the urgent need for adaptive strategies to address anxiety and combat systemic inequities.

  • Research Article
  • 10.1038/s41598-026-36811-9
The changed endemic pattern of human adenovirus from species C to B among children in 2022-2024 in Shenzhen, China.
  • Jan 21, 2026
  • Scientific reports
  • Dan-Dan Niu + 19 more

Respiratory human adenovirus (HAdV) infections pose a significant threat to children's health. This study investigated the prevalence and molecular epidemiology of respiratory HAdV in children from both hospital and community settings in Shenzhen between 2022 and 2024. Children under 14 years of age with suspected acute respiratory infections were enrolled from eight hospitals between November 2022 and June 2024, as well as from communities between October 2023 and April 2024 in Shenzhen. Respiratory specimens were collected and tested for HAdV. The positive rates of HAdV across different groups were compared using Pearson's chi-square test with the Bonferroni correction, and phylogenetic analysis was performed on the detected HAdV strains. The positivity proportion of HAdV among children in hospital was 16.7% (83/498) between September 2023 and June 2024, predominantly involving HAdV-B3 (95.2%, 20/21). This rate was significantly higher than that observed from October 2022 to June 2023 (3.4%, 11/321) (χ² = 33.676, P < 0.001), during which HAdV-C1 was the predominant subtype (77.8%, 7/9). The positive proportion of HAdV in hospitalized children was higher than that in outpatient children (χ2 = 0.275, P < 0.001), and the positive proportion of HAdV in boys was lower than that in girls in community (χ2 = 4.843, P = 0.028). No significant difference in the mean age was observed between children infected with HAdV-B and those with HAdV-C (t = 0.670, P = 0.509). The Shenzhen-2023-2-ILI-P600 strain exhibited a deletion in the 362-365 aa region of its Penton base gene. Analysis of global HAdV-C1 strains revealed that aa differences at positions 339 and 472 of the Fiber gene were closely linked to specific evolutionary branches. Global HAdV-B3 strains, while highly conserved, showed branch-associated aa differences at positions 168, 403, and 541 of the Hexon gene. The rise in HAdV positivity among pediatric patients in Shenzhen hospitals from late 2022 to late 2023 coincided with a shift in the dominant type from HAdV-C1 to HAdV-B3. Branch-specific aa differences were identified in the Fiber gene of HAdV-C1 and the Hexon gene of HAdV-B3.

  • Research Article
  • 10.30934/kusbed.1803934
Challenges in the Diagnosis of Extrapulmonary Tuberculosis and Comparison of Diagnostic Methods
  • Jan 20, 2026
  • Kocaeli Üniversitesi Sağlık Bilimleri Dergisi
  • Özlem Güler + 5 more

Objective: Diagnosing extrapulmonary tuberculosis (EPTB) is difficult because of its paucibacillary nature and the need for invasive sampling. This study evaluated the diagnostic performance and inter-test agreement of commonly used methods and identified demographic and clinical features that may assist diagnosis. Methods: This retrospective cohort study was conducted at a tertiary care hospital (2018–2025). EPTB was defined as at least one positive result from acid-fast bacilli (AFB) smear microscopy, polymerase chain reaction (PCR), solid or automated liquid cultures. Demographics, comorbidities, symptoms, laboratory results, histopathological and radiological findings were obtained from medical records. The positivity proportions were calculated, and agreement was assessed using the kappa coefficient. Results: 46 adult patients with EPTB were included. The mean age was 51.6 ± 20.1 years, with female predominance (67.4%). The most frequent sites were the lymph nodes (32.6%), genitourinary tract (21.7%), and musculoskeletal system (21.7%). The highest positivity was observed with automated liquid culture (76.1%), followed by solid culture (71.7%) and PCR (59.5%); AFB smears had the lowest rate (19.6%). Granulomatous inflammation was detected in 63.2% of patients who underwent pathological examination and caseous necrosis in 36.8%. There was slight agreement between AFB smear microscopy, culture, and histopathology. PCR results showed poor agreement with solid and automated liquid cultures, including negative kappa values. Radiological examinations revealed pathological findings in 88.2% of patients, predominantly lymphadenopathy. Conclusion: Clinical and laboratory diagnosis of EPTB remains challenging. These findings support a multimodal strategy that integrates microbiological, molecular, histopathological, and radiological methods to improve diagnostic accuracy.

  • Research Article
  • 10.1093/imrn/rnaf381
On Signs of Fourier Coefficients on GL( n )
  • Jan 13, 2026
  • International Mathematics Research Notices
  • Didier Lesesvre + 2 more

Abstract We study statistical properties of Fourier coefficients of automorphic forms on $\textrm{GL}(n)$. For most Hecke–Maass cusp forms, we give the asymptotic number of nonvanishing coefficients, show that there is a positive proportion of sign changes among them when these are real, and describe the asymptotic density of these signs. We generalize the results of Jääsaari obtained in the case of self-dual forms on $\textrm{GL}(3)$ to almost all forms on $\textrm{GL}(n),$ and our method moreover circumvents the assumption of the Generalized Ramanujan Conjecture.

  • Research Article
  • 10.1093/ofid/ofaf695.656
P-441. Epidemiology of Pediatric Mycoplasma pneumoniae (MP) Infections at Two Pediatric Hospitals in Los Angeles County (LAC), January 1, 2017 to January 31, 2025
  • Jan 11, 2026
  • Open Forum Infectious Diseases
  • Heidi Ransohoff + 6 more

Abstract Background In May 2024, LAC Department of Public Health (DPH) received reports about increased pediatric MP infections. In October 2024, the U.S. Centers for Disease Control and Prevention (CDC) reported a national increase in MP infections and hospitalizations among young children. We describe pediatric MP infections from 2017 to 2025 in LAC and compare case characteristics between pre- and post-pandemic periods. Methods LAC DPH conducted a retrospective cohort study of patients &amp;lt; 18 years seen at two LAC healthcare systems (HS1 and HS2) who tested MP positive by respiratory pathogen panel (RPP) or single target molecular test between January 1, 2017 and January 31, 2025. Positive patients were identified through lab data; HS2 also used electronic health records. Pre- and post-pandemic were defined as before March 12, 2020 and after March 31, 2023, respectively. χ2and Wilcoxon-Mann-Whitney tests were used to assess relationships between characteristics and pre- and post-pandemic periods. Data analysis was performed in SAS 9.4. Results Of 865 positive patients, 561 were reported from HS1; 287 were reported form HS2. 156 infections occurred pre-pandemic, 22 during the pandemic, and 687 post-pandemic (Figure 1). On average, there were 4 positive patients reported per month pre-pandemic and 31 positive patients reported per month post-pandemic. HS1 and HS2 reported fewer inpatient positive patients post-pandemic compared to pre-pandemic (p &amp;lt; .05; Table 1). HS1 detected 11% of their tests via RPP; HS2 detected 99% of their tests via RPP. Overall, 484 (56%) patients were male and 384 (44%) were female. Pre- and post-pandemic, the median age was 6 and 8 years old, respectively (p &amp;lt; .0001). Conclusion The number of MP positive patients and proportion of outpatient cases greatly increased post-pandemic, which may be due to increased testing of mild cases. Data on changes in age distribution of cases post-pandemic are varied; in this study the median age of patients increased after the pandemic, which may be due to a larger susceptible population post-pandemic. The proportion of cases identified using an RPP versus a dedicated PCR varied between HS1 and HS2, which may affect sensitivity. Further studies should be conducted to better understand MP epidemiology post-pandemic. Disclosures All Authors: No reported disclosures

  • Research Article
  • 10.1016/s2214-109x(25)00437-1
HIV testing during systematic screening for tuberculosis among household contacts in high-tuberculosis burden settings: a systematic review and meta-analysis.
  • Jan 1, 2026
  • The Lancet. Global health
  • Peter Scott + 10 more

HIV testing during systematic screening for tuberculosis among household contacts in high-tuberculosis burden settings: a systematic review and meta-analysis.

  • Research Article
  • 10.4064/aa250411-9-10
Fermat pseudoprimes
  • Dec 29, 2025
  • Acta Arithmetica
  • Shuguang Li + 1 more

We give an upper bound for the distribution of base-a pseudoprimes that is uniform in the base and does not require coprimality to the base. In addition we show that there are infinitely many “near Carmichael numbers” meaning that they are pseudoprimes for a positive proportion of bases, but not all bases.

  • Research Article
  • 10.1186/s12879-025-12350-y
The multipathogen profiles and co-infection characteristics obtained from comprehensive surveillance of patients with acute respiratory infections in the post-COVID-19 era in Shenzhen, China
  • Dec 17, 2025
  • BMC Infectious Diseases
  • Dandan Niu + 17 more

BackgroundThe long-term impact of the COVID-19 pandemic on the distribution pattern of respiratory pathogens in China was unknown. Our study aimed to determine the multipathogen profiles and co-infection characteristics among patients with acute respiratory infections (ARIs) in the post-COVID-19 era in Shenzhen, China.MethodsThis multi-center cross-sectional study was conducted among patients with ARIs from five sentinel hospitals from November 1, 2022 to June 30, 2023 in Shenzhen, China. The collected respiratory samples were subjected to targeted next-generation sequencing for high-throughput screening of 108 respiratory pathogens. Multi-stage logistic regression models were built to infer interactions between pathogens at the individual level.ResultsThe median [IQR] age of 1890 patients included was 31.8 [23.7, 45.2] years. The proportions of positivity on any pathogen and co-infection were 84.0% (1587/1890) and 41.4% (782/1890). Children < 5 years and school-age children have the highest viral (78.0%, 99/127) and bacterial positive proportion (65.5%, 114/127). Influenza virus (IFV), SARS-CoV-2, and human rhinovirus (HRV) were the three leading viral pathogens, and Haemophilus influenzae (H. influenzae), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae) were the three leading bacterial pathogens. The three leading co-infection pathogens were S. pneumoniae combined with H. influenzae (4.6%, 86/1890), IFV with S. aureus (4.5%, 85/1890) and with H. influenzae (3.3%, 62/1890). The proportions of positivity on IFV, enterovirus, SARS-CoV-2, H. influenzae, S. aureus, and S. pneumoniae in outpatients were higher than those in inpatients, while the proportions of positivity on human parainfluenza virus (HPIV), human metapneumovirus (HMPV), Pseudomonas aeruginosa, Acinetobacter baumannii, Mycoplasma pneumoniae, and Legionella pneumophila in inpatients were higher than those in outpatients. RSV, IFV, HPIV, human adenovirus, and HRV were the top five viral pathogens among hospitalized children before, during, and after the COVID-19 pandemic in Shenzhen. Virus‒virus interactions, such as IFV combined with SARS-CoV-2 (OR = 20.3 [95% confidence interval (CI): 7.2–57.0]) and with HRV (OR = 7.2 [95% CI: 3.5–15.0]) exhibited competitive effects. Bacteria-bacteria interactions exhibited synergistic effects such as Moraxella catarrhalis combined with S. pneumoniae (OR = 0.3 [95% CI: 0.2–0.5]).ConclusionsThere were differences in the pathogen profiles among patients with different ages, pneumonia groups, and case types. Virus‒virus interactions presented competitive effects, while bacterium‒bacterium interactions exhibited synergistic effects.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-025-12350-y.

  • Research Article
  • 10.1007/s00125-025-06618-w
Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice.
  • Dec 11, 2025
  • Diabetologia
  • Chenyang Fu + 16 more

Diet switch during weaning induces gut microbiome maturation, accompanied by the formation of adequate functional beta cell mass. Bile acid (BA), an essential microbial metabolite, regulates host glucose homeostasis by binding to its main receptor, farnesoid X receptor (FXR, encoded by NR1H4). However, the precise roles of microbial BA metabolism and FXR signalling in neonatal beta cell development are still unclear. Islet FXR levels were determined at different perinatal stages. Postnatal changes in gut microbiome and BA profiles were examined in mice, with changes in germ-free mouse BAs serving as the control. We genetically modified beta cells to sustain FXR expression after birth (using Nr1h4-knockin [βFxrKI] mice) and performed morphological and functional analysis on murine islets. Single-cell RNA-seq and single-cell assay for transposase-accessible chromatin sequencing of islet cells were used to study FXR-mediated downstream regulation in islets. Lineage tracing was performed to evaluate beta cell fate transition. Mendelian randomisation (MR) and human islet proteomics data analysis were applied to study the pathological relevance in human diabetes. FXR expression in beta cells declined after birth (positive cell proportion, 29.1±3.1% at embryonic day 18.5 vs 4.2±2.4% at 3 weeks postnatal in mice, p<0.001). This physiological change paralleled the ascending of FXR-agonistic BAs derived from gut microbiome maturation (unconjugated BA proportion, 0.9±0.6% at 1 week vs 14.0±5.6% at 3 weeks, p<0.05). βFxrKI mice had limited beta cell mass growth (approximately 70% of the control level at 1 week of age and only 15% of the control level at 8 weeks of age) and developed high blood glucose levels by weaning (random blood glucose, 15.2±1.7 mmol/l in βFxrKI vs 7.7±0.5 mmol/l in control, p<0.001), mainly resulting from elevated cell apoptosis (1.95-, 1.79-, and 3.27-fold increase vs control at 1, 2 and 3 weeks, respectively) and altered beta cell identity. Casp6 was identified as a key downstream target in beta cell FXR. Intervention with antibiotics or a specific caspase-6 (CASP6) inhibitor partially recovered the phenotypes of βFxrKI mice. Further validation in humans showed that islet FXR/CASP6 levels were elevated in individuals with type 2 diabetes (FXR, -0.039±1.257 a.u.in donors without diabetes vs 0.646±1.140 a.u. in donors with diabetes, p=0.0371; CASP6, -1.575±0.307 a.u.in donors without diabetes vs -1.325±0.381 a.u.in donors with diabetes, p=0.011). MR analysis further supported the effect of human islet FXR expression in elevating HbA1c (β=0.006, p<0.001) with lowering fasting insulin level (β=-0.009, p=0.02) and the effect of CASP6 expression in enhancing 2 h glucose (β=0.039, p=0.01). The declining FXR-CASP6 signals in neonatal beta cells could serve as a programmed host response to the maturing gut microbial BA metabolism to maintain normal postnatal beta cell mass development and ensure glycaemic homeostasis in adults. Raw data of scRNA-seq and scATAC-seq are deposited in the Gene Expression Omnibus (GEO) database under the accession number GSE241408. The code used in this Mendelian randomisation study is publicly available at https://github.com/Angela-linyt/Gene_Glu_MR.git .

  • Research Article
  • 10.1007/s12672-025-04198-0
Blood ctDNA-specific markers predict the risk of peritoneal metastasis for advanced gastric cancer
  • Dec 6, 2025
  • Discover Oncology
  • Fangzhou Xing + 5 more

ObjectiveThe aim of this study was to investigate the value of early postoperative ctDNA dynamic monitoring (TP53/KRAS/PIK3CA gene mutations) combined with clinicopathologic factors in risk stratification of postoperative peritoneal metastasis in advanced gastric cancer.MethodsOne hundred and twenty-eight patients with advanced gastric cancer (stage II/III) who underwent R0 resection were enrolled, of whom 32 developed peritoneal metastasis after surgery (peritoneal metastasis group) and 96 did not (non-peritoneal metastasis group). The study collected peripheral blood samples from patients at 7 days (T0) and 4 weeks (T1) after surgery, detected mutations in ctDNA at three loci, TP53 p.R248W, KRAS p.G12D, and PIK3CA p.H1047R, by ddPCR and simultaneously collected clinicopathological features such as Lauren classification and serosal invasion. The primary endpoint was peritoneal metastatic events confirmed by imaging or pathology.ResultsThe proportion of Lauren diffuse-type peritoneal metastases (65.6% vs. 34.4%, P = 0.002), serosal invasion (87.5% vs. 65.6%, P = 0.018), and persistent ctDNA positivity (53.1% vs. 19.8%, P < 0.001) were significantly higher. The Boruta algorithm identified Lauren diffuse type, serosal invasion, and persistent ctDNA positivity as key variables. The combined model (Model 1) constructed based on these variables demonstrated optimal performance (C-index = 0.853) and significantly outperformed the traditional clinical model (C-index = 0.840). A nomogram developed from this model enables personalized risk prediction. Based on the number of risk features (≥ 2 features in the high-risk group and ≤ 1 feature in the low-risk group), Kaplan-Meier analysis showed that the cumulative incidence of peritoneal metastasis was significantly higher in the high-risk group (51 cases) than in the low-risk group (77 cases) (Log-rank P = 0.0012).ConclusionEarly postoperative persistent ctDNA positivity (especially TP53 mutation) combined with Lauren diffuse-type classification and serosal invasion can effectively identify patients at high risk of peritoneal metastasis. This integrated model provides a new strategy for precise postoperative surveillance and intervention in advanced gastric cancer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12672-025-04198-0.

  • Research Article
  • 10.4038/sljahs.v1i1.1
Blood Culture Positivity Rates among Babies Admitted to the Premature Baby Unit of a Secondary Care Hospital in Southern Sri Lanka: An Analysis of Microbial Isolates and Antimicrobial Susceptibility Patterns
  • Dec 5, 2025
  • The Sri Lankan Journal of Allied Health Sciences
  • Mm Rathnayake + 2 more

Bloodstream infections are a major cause of morbidity and mortality among babies in premature baby units (PBU). Periodic monitoring of the antimicrobial sensitivity of the causative organisms in a particular setting is important for the early management of infections in babies. The aim of this study was to determine the proportion of blood culture positivity and to assess the factors associated with bloodstream infections among the babies and the causative microorganisms and their antibiotic susceptibility pattern, isolated in blood cultures of babies with suspected sepsis admitted to PBU at District General Hospital Matara (DGHM). All institution based cross-sectional study was conducted in microbiology laboratory at DG HM to review blood culture reports received from PBU retrospectively. All the consecutive samples from the PBU from January 2021 to December 2022 were included in the study. Data on culture isolates, antibiotic susceptibility patterns and related variables were collected and analysed using SPSS version 25.0. Over the study., 1612 blood cultures had been sent to the laboratory from the PBU. Overall blood culture positivity rate was 9%. The majority of isolates were gram-positive organisms (68%). Coagulase-negative staphylococci (51.6%) were the most common isolates, followed by lactose fermenting coliforms (16%) and Pseudomonas spp. (8%). Amikacin showed a higher sensitivity then gentamicin among gram-negative organisms. Carbapenem resistance was observed in 40.5% of the isolates. Among Staphylococcus aureus 55.6% were methicillin-resistant and 44.4% were methicillin sensitive. Prematurity (p=0.017) and low birth weight (p=0.002) were significantly associated with culture positive sepsis. Preterm and low birth weight were significantly associated with blood stream infections among babies admitted to PBU of DGHM. Coagulase-negative Staphylococci, lactose fermenting coliforms, and Pseudomonas spp. were the predominant causative organisms.

  • Research Article
  • 10.1016/j.diabres.2025.112977
Islet autoimmunity in young First Nations women with prediabetes and type 2 diabetes.
  • Dec 1, 2025
  • Diabetes research and clinical practice
  • Mary M Wicks + 8 more

Islet autoimmunity in young First Nations women with prediabetes and type 2 diabetes.

  • Research Article
  • 10.1016/j.vaccine.2025.127931
Limitations of serological screening for measles immunity in young health care workers in New Zealand.
  • Dec 1, 2025
  • Vaccine
  • Sumanta Saha + 5 more

Limitations of serological screening for measles immunity in young health care workers in New Zealand.

  • Research Article
  • 10.1016/j.clineuro.2025.109204
Predictive potential of radiographic characteristics on outcomes after Chiari Decompression surgery: A meta-analysis of the literature.
  • Dec 1, 2025
  • Clinical neurology and neurosurgery
  • Ankita Jain + 8 more

Predictive potential of radiographic characteristics on outcomes after Chiari Decompression surgery: A meta-analysis of the literature.

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