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Nevin Manimala Statistics

Mut-p53 acts as a synthetic lethal partner with E2F3 inhibition in gastric cancer under FGFR1 inhibitor

Cell Signal. 2026 Aug 22:112838. doi: 10.1016/j.cellsig.2026.112838. Online ahead of print.

ABSTRACT

BACKGROUND: Gastric cancer frequently harbors TP53 mutations, posing a challenge for therapies directly targeting mutant p53. Fibroblast growth factor receptor 1 (FGFR1) is a potential therapeutic target, but its interaction with mutant p53 in gastric cancer remains poorly understood.

METHODS: We evaluated our newly designed FGFR1 inhibitor, S29, across multiple gastric cancer cell lines. Synthetic lethal partners of mutant p53 were identified using the Synthetic Lethality Online Analysis Database and validated through molecular assays, including overexpression and knockdown of p53 and E2F3. Clinical tissue samples were analyzed to confirm the pathological relevance of the FGFR1-E2F3-p53 axis.

RESULTS: S29 effectively suppressed gastric cancer cell growth while concurrently increasing mutant p53 expression and downregulating E2F3. We identified E2F3 as a synthetic lethal partner of mutant p53. While p53 knockdown abolished S29’s inhibitory effects, the combination of mutant p53 accumulation and FGFR1-mediated E2F3 inhibition significantly triggered G2/M cell cycle arrest and programmed cell death. These findings were consistent with expression patterns observed in clinical samples.

CONCLUSIONS: Our study demonstrates that FGFR1 inhibition induces synthetic lethality in mutant p53 gastric cancer by targeting the E2F3 axis. These results suggest that S29 provides a strategic therapeutic approach for patients with TP53 mutations.

PMID:42632533 | DOI:10.1016/j.cellsig.2026.112838

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Nevin Manimala Statistics

Comparative Image-Based Evaluation of Deep Learning Models for the Diagnosis of Different Ocular Diseases in Cats

Vet J. 2026 Aug 22:106846. doi: 10.1016/j.tvjl.2026.106846. Online ahead of print.

ABSTRACT

Ocular pathologies are a leading cause of visual impairment in cats and require accurate, timely diagnosis for effective treatment. This study aimed to comparatively evaluate the performance of different deep learning (DL) architectures for the automated identification and classification of feline ophthalmic disease. A dataset of 456 clinically validated ocular images, spanning 13 classes (12 ocular diseases and a healthy group), was used to train nine convolutional neural network (CNN) architectures, including ResNet, EfficientNet, DenseNet, MobileNet, and VGG models, through transfer learning with pre-trained ImageNet weights. Data augmentation and five-fold cross-validation were applied during training. Statistical significance of performance differences across architectures was assessed using Cohen’s Kappa and McNemar’s test. On the held-out test set, EfficientNet-B0 reached the highest classification accuracy (78%), while DenseNet-121 obtained the highest macro-averaged F1-score (0.76) and Area Under the Curve (AUC) (0.9790), followed by EfficientNet-B0 (0.9750) and ResNet-34 (0.9724). Confusion matrix analysis showed the strongest classification consistency for cherry eye, healthy, and corneal sequestration (precision and recall reaching 1.00 in several cases), and the weakest for glaucoma (recall 0.25) and corneal ulcer (F-1 score 0.29). McNemar’s test indicated no statistically significant difference among EfficientNet-B0, DenseNet-121, and ResNet-34 (p>0.05), and per-image inference times across all nine architectures ranged from 2.67 to 5.73 ms. Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations applied to the EfficientNet-B0 model confirmed that the model focused on clinically relevant ocular regions during classification. Overall, the results obtained with EfficientNet-B0, DenseNet-121, and ResNet-34 suggest that DL-based multi-class classification could support clinical decision-making in the diagnosis of feline ophthalmic diseases.

PMID:42632482 | DOI:10.1016/j.tvjl.2026.106846

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Nevin Manimala Statistics

Seroprevalence, epidemiological factors, and spatial patterns of exposure to Trypanosoma cruzi in urban cats in Maceió, Northeastern Brazil

Vet J. 2026 Aug 22:106843. doi: 10.1016/j.tvjl.2026.106843. Online ahead of print.

ABSTRACT

Domestic cats have been recognized as potential environmental sentinels for zoonoses due to their proximity to human populations, wide distribution in urban environments, and exposure to multiple pathogen transmission routes. In the context of Chagas disease, however, studies assessing serological exposure in cats in urban areas of Northeastern Brazil remain scarce. Thus, this study aimed to estimate the seroprevalence of anti-Trypanosoma cruzi IgG antibodies and to describe spatial patterns of seroreactivity in urban cats in the municipality of Maceió, Alagoas, Brazil. A total of 366 cats older than six months were included, comprising 267 owned cats and 99 animals rescued by the Zoonosis Control Center of Alagoas. Detection of anti-T. cruzi IgG antibodies was performed using the Indirect Immunofluorescence Assay (IFA). Spatial analysis was conducted in a descriptive and exploratory manner using point maps and Kernel density estimates. The observed seroprevalence was 7.6% (28/366; 95% CI: 5.4-10.8%). No statistically significant associations were identified between seropositivity and “animal condition,” “sex,” “age group,” or “breed.” Spatial analysis revealed a heterogeneous distribution of sampled cats, with higher concentrations in the western and southwestern portions of the municipality. Seroreactive cases were spatially dispersed and largely overlapped with areas of greater sampling intensity. Kernel density surfaces for cases and sampling effort showed similar patterns. These findings indicate serological evidence of exposure to T. cruzi in urban cats in Maceió and reinforce the importance of integrated, multispecies approaches in Chagas disease surveillance.

PMID:42632479 | DOI:10.1016/j.tvjl.2026.106843

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Nevin Manimala Statistics

Gestational diabetes and maternal morbidity in multifetal pregnancies: independent contributions of GDM and plurality

Diabetes Res Clin Pract. 2026 Aug 22:113517. doi: 10.1016/j.diabres.2026.113517. Online ahead of print.

ABSTRACT

AIMS: To evaluate the independent and combined associations of gestational diabetes mellitus (GDM) and multifetal gestation with maternal morbidity, particularly hypertensive disorders of pregnancy (HDP).

METHODS: We conducted a national multicenter retrospective cohort study from six university-affiliated medical centers (2010-2024) mapped to the OMOP Common Data Model. Pregnancies were categorized as singleton without GDM, singleton with GDM, multifetal without GDM, and multifetal with GDM. Outcomes included HDP, ICP, cesarean delivery, and placental abruption. Multivariable Firth logistic regression adjusted for maternal age, body mass index, parity, and fertility treatment.

RESULTS: Among 134,517 pregnancies, HDP rates increased from 4.5% in singleton pregnancies without GDM to 10.2% in singleton pregnancies with GDM, 11.0% in multifetal pregnancies without GDM, and 16.4% in multifetal pregnancies with GDM. GDM was independently associated with HDP (aOR 1.7, 95% CI 1.6-1.8). Multifetal gestation showed stronger associations with HDP (aOR 2.2-2.5) and severe preeclampsia (aOR 3.6). ICP was most frequent in multifetal pregnancies with GDM (aOR 6.5,95% CI 3.5-10.9). No statistically significant interaction between GDM and multifetal gestation was detected for HDP(q = 0.088).

CONCLUSION: Both GDM and multifetal gestation were independently associated with maternal morbidity. Multifetal gestation showed stronger associations with hypertensive outcomes, without evidence of interaction between the two exposures.

PMID:42632456 | DOI:10.1016/j.diabres.2026.113517

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Methodological contributors to estrous-cycle variability in DHEA-induced mouse models of polyendocrine metabolic ovarian syndrome

J Steroid Biochem Mol Biol. 2026 Aug 22:107106. doi: 10.1016/j.jsbmb.2026.107106. Online ahead of print.

ABSTRACT

Dehydroepiandrosterone (DHEA)-induced rodent models are widely used in polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome [PCOS]) research, yet their reproducibility is limited by substantial methodological variability. While rats are often reported to exhibit diestrus arrest, mouse studies describe estrus-dominant or mixed-stage arrest, differences frequently attributed to species effects; however, heterogeneity in experimental design may also contribute. We synthesized 25 published DHEA-induced rodent studies and characterized estrous-cycle dynamics in a C57BL/6 model using one commonly used DHEA protocol. Key methodological variables-including induction age, DHEA brand and solvent, dosage, administration duration, smear-sampling timing, and cytological criteria-were extracted and examined using a semi-quantitative comparative approach. Estrous-arrest patterns were compared across methodological subgroups to formulate provisional, evidence-informed recommendations. Substantial variability in estrous-arrest patterns was identified across studies, although subgroup differences were not statistically significant. Approximately 60% of C57BL/6 studies reported estrus-dominant arrest when DHEA was administered at 6mg/100g body weight, sesame oil was used as the solvent, and induction began before postnatal day 28. Our experiment confirmed that the selected protocol can produce estrus-dominant arrest, but it did not compare alternative doses, solvents, induction ages, or sampling schedules. Directional trends suggested that DHEA dosage, solvent type, and induction age may contribute to estrous outcomes. Overall, methodological factors may contribute substantially to estrous-cycle variability in DHEA-induced mouse models; however, the available evidence does not establish them as dominant or causal determinants. These findings identify candidate methodological contributors and support provisional recommendations to improve reporting and cross-study comparability, while direct comparative experiments integrating endocrine and ovarian endpoints remain necessary for validation.

PMID:42632429 | DOI:10.1016/j.jsbmb.2026.107106

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Nevin Manimala Statistics

Pollution characteristics, risk assessment, and environmental associations of microplastics and antibiotic resistance genes in tropical marine aquaculture: A comparative study across different farming systems in Hainan

Mar Pollut Bull. 2026 Aug 22;233(Pt 2):120282. doi: 10.1016/j.marpolbul.2026.120282. Online ahead of print.

ABSTRACT

Microplastics (MPs) and antibiotic resistance genes (ARGs) were compared across four marine aquaculture systems in Hainan (fish, shrimp, fish-shrimp mixed, and snail farms). MPs averaged 4.90 ± 5.50 items·L-1, with polyethylene, rayon, polypropylene-polyethylene copolymer, and polystyrene as dominant polymers. Fibers (58.90%) and 100-500 μm particles prevailed. Snail farms showed the highest MP concentration (6.62 ± 1.68 items·L-1), while others ranged from 2.02 to 2.90 items·L-1. The Pollution Load Index indicated low contamination overall, but snail farms posed the highest potential ecological risk. A total of 130 ARGs belonging to 11 classes and 13 MGEs belonging to 6 classes were detected, with fish farms showing higher ARG abundance and fish-shrimp mixed systems showing higher MGE abundance. MGEs showed strong correlations with ARGs, indicating potential associations with ARG mobility rather than direct evidence of horizontal gene transfer. Salinity and specific conductance showed potential associations with ARG distribution, but these relationships should be interpreted as exploratory rather than statistically confirmed drivers. Risk Quotient (RQ) analysis revealed the highest combined ARG risks in shrimp and mixed farms, followed by fish, then snail farms. Tetracycline resistance genes dominated risk, reaching an RQ of 1772.14 in shrimp farms. The study provides system-specific insights into MP and ARG pollution and risks, supporting targeted monitoring and management in tropical marine aquaculture.

PMID:42632386 | DOI:10.1016/j.marpolbul.2026.120282

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Nevin Manimala Statistics

Real-world evolution of therapeutic strategies and outcomes in acquired thrombotic thrombocytopenic purpura: a 14-year referral center experience

Med Clin (Barc). 2026 Aug 22;166(10):107588. doi: 10.1016/j.medcli.2026.107588. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Acquired or immune thrombotic thrombocytopenic purpura (iTTP) is a rare thrombotic microangiopathy caused by autoantibodies against ADAMTS13. The aim of this study was to evaluate the efficacy and safety of caplacizumab (CPZ) and rituximab (RTX) added to standard therapy in a real-world cohort.

METHODS: A single-center retrospective observational study of all adult patients with iTTP treated at Hospital Universitari de Bellvitge (2010-2024). Efficacy and safety variables were compared between patients treated with CPZ added to standard therapy versus those who were not, between patients who received RTX versus those who did not, and finally between quadruple therapy (corticosteroids [CS] + plasma exchange [PEX] + CPZ + RTX) and dual therapy (CS + PEX).

RESULTS: Thirty patients were included (46 acute episodes). CPZ was significantly associated with a shorter time to clinical response (5 vs. 9days; P=.023), shorter time to remission (24.8 vs. 40.6days; P<.001), and fewer plasma exchange sessions (5.5 vs. 9.5 sessions; P<.001). Early administration (<72hours) was associated with a shorter hospital stay (11 vs. 19.5days; P=.012). RTX showed a reduction in the number of relapses (13.3% vs. 50%; P=.085), without reaching statistical significance. Both drugs showed favorable safety profiles. Quadruple therapy resulted in a shorter time to clinical remission (26.1±9.9 vs. 40.3±7days; P<.001) and a lower number of PEX sessions (6 [4-7] vs. 8 [7-15.8]; P=.034).

CONCLUSIONS: In iTTP, CPZ improves short-term outcomes, particularly when administered early. RTX is associated with a trend toward greater relapse-free survival. Quadruple therapy reduces the time to clinical remission and the number of plasma exchange sessions. In iTTP, the incorporation of targeted and personalized therapeutic advances into clinical practice is associated with an improvement in clinical outcomes.

PMID:42632382 | DOI:10.1016/j.medcli.2026.107588

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Urban wildlife as a reservoir of zoonotic pathogens: A multi-pathogen qPCR survey from a Central European City

Vet Microbiol. 2026 Aug 16;321:111194. doi: 10.1016/j.vetmic.2026.111194. Online ahead of print.

ABSTRACT

Urbanization alters wildlife communities and creates epidemiological bridges between wild, domestic, and synanthropic hosts. Data on multiple pathogen taxa circulating simultaneously in urban mammals in Central Europe remain limited. Between July 2023 and July 2025, 240 wild mammals (native and invasive) were collected in the urban and peri-urban district of Brno, Czech Republic. Intestinal content, tongue, lymph nodes and other organs were examined using multiplex qPCRs for selected viral, bacterial and parasitic pathogens, including hepatitis E virus (HEV), Francisella tularensis, Echinococcus multilocularis, Toxoplasma gondii, Toxocara spp., Baylisascaris procyonis and others. Basic statistical analyses were used to explore risk factors and co-infections. Overall, 43.3% animals were positive for at least one pathogen. Multiple tissue positivity either with the same or more pathogens was observed. The work showed first molecular evidence of HEV and F. tularensis in free-ranging European raccoon dogs, and HEV in stray cats. Highest prevalence was observed for Toxocara spp. in cats and red foxes. E. multilocularis, Toxocara spp. and B. procyonis were detected across several hosts. Strong associations were found between Toxocara and B. procyonis in cats and between Giardia duodenalis and Cryptosporidium parvum in cats. Age was identified as a significant factor with young foxes being infected more frequently by Toxocara than adults. These findings indicate substantial pathogen circulation and environmental contamination within urban adapted mammals. The pilot study provides a multi-pathogen baseline for urban wildlife in Central Europe and underscores the need for integrated, long-term One Health surveillance.

PMID:42632371 | DOI:10.1016/j.vetmic.2026.111194

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Comparative efficacy of the femoral neck system, cannulated cancellous screws combined with medial buttress plate, and cannulated cancellous screws in the treatment of femoral neck fractures in young and middle-aged adults

Injury. 2026 Aug 11;57(10):113539. doi: 10.1016/j.injury.2026.113539. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the long-term efficacy of the Femoral Neck System (FNS), cannulated cancellous screws (CCS) combined with a medial buttress plate (MBP), and CCS alone in treating femoral neck fractures in young and middle-aged adults, and to identify independent risk factors for postoperative complications.

METHODS: This retrospective single-center study enrolled 355 patients with femoral neck fractures. The inclusion criteria were patients aged 18-65 years with complete baseline data and a mean follow-up duration of 18.22 ± 6.31 months. Exclusion criteria included pathological/bilateral fractures and significant comorbidities. Based on the surgical technique employed, patients were assigned to the FNS group (n = 165), CCS+MBP group (n = 62), or CCS group (n = 128). Baseline characteristics, surgical parameters, radiographic outcomes (Garden index), complication rates, and functional outcomes were compared among the groups. Statistical analyses included one-way ANOVA, χ² tests, and multivariate logistic regression.

RESULTS: Baseline characteristics were comparable across the three groups. Mean fracture healing time was 13.30±1.34 weeks for CCS, 11.42±1.02 weeks for CCS+MBP, and 11.62±1.23 weeks for FNS (P = 0.224). At the 3-month postoperative assessment, the CCS+MBP group demonstrated significantly different functional outcomes compared to both the FNS and CCS groups. Specifically, the Harris Hip Score (HHS) results were 61.43±2.74 for CCS + MBP vs 58.43±2.08 for FNS vs 54.31±2.63 for CCS (P < 0.001); the OHS results were 37.32±2.31 for CCS+MBP vs 43.07±2.92 for FNS vs 42.86±2.90 for CCS (P < 0.001). At 6 months and the final follow-up, no significant differences in HHS or OHS were observed among the groups. Overall complication rates were 16.41% for CCS, 12.90% for CCS+MBP, and 15.15% for FNS (P = 0.819); specifically, femoral neck shortening occurred in 3.91%, 4.84%, and 9.09% (P = 0.171), and osteonecrosis in 7.81%, 4.84%, and 3.64% (P = 0.284), respectively. Multivariate logistic regression identified implant removal (OR=5.56, 95%CI 2.51-12.32, P < 0.001), medial cortex comminution (OR=2.62, 95%CI 1.20-5.73, P = 0.016), Pauwels type III fracture (OR=3.51, 95%CI 1.30-9.50, P = 0.013), and reduction quality Garden index III (OR=2.78, 95%CI 1.98-7.90, P = 0.048) or IV (OR=4.43, 95%CI 1.40-14.00, P = 0.011) as independent risk factors for postoperative complications, whereas Garden index II was protective (OR=0.28, 95%CI 0.10-0.84, P = 0.023).

CONCLUSION: CCS+MBP accelerates early functional recovery but confers no long-term advantage over FNS or CCS, while introducing greater surgical trauma. It is not yet justified to replace FNS or CCS universally. Individualized implant selection and strict control of identified risk factors remain central to optimizing outcomes.

PMID:42632352 | DOI:10.1016/j.injury.2026.113539

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Postpartum glucose follow-up after gestational diabetes in China: provider and institutional determinants in a multicenter survey across urban public hospitals

Front Endocrinol (Lausanne). 2026 Aug 7;17:1887259. doi: 10.3389/fendo.2026.1887259. eCollection 2026.

ABSTRACT

BACKGROUND: Postpartum glucose follow-up after gestational diabetes mellitus (GDM) represents an important opportunity for early diabetes risk identification and long-term type 2 diabetes prevention. Obstetric healthcare professionals play a key role in initiating postpartum follow-up, yet evidence on provider- and institution-related factors influencing implementation in routine obstetric care remains limited.

METHODS: A multicenter cross-sectional survey was conducted among 638 obstetric healthcare professionals from 128 participating urban public hospitals across 15 provinces in China. A self-developed questionnaire was refined through two rounds of Delphi expert consultation and evaluated using exploratory factor analysis. Data were analysed using descriptive statistics, Pearson’s correlation analysis, Mann-Whitney U tests, Kruskal-Wallis H tests, and robust regression based on a generalised linear model.

RESULTS: Mean scores for knowledge, professional beliefs, and practice were 4.07 ± 0.57, 3.99 ± 0.40, and 3.89 ± 0.73, respectively, indicating that practice lagged behind knowledge and professional beliefs. Knowledge was positively correlated with professional beliefs (r = 0.473, P < 0.001) and practice (r = 0.630, P < 0.001). Participation in specialised GDM training, experience working in a specialist GDM clinic, and self-reported mastery of relevant knowledge were associated with higher scores across domains. Hospital-level differences were observed for practice scores, but these differences did not indicate a simple gradient by hospital level.

CONCLUSION: This study suggests that implementation of postpartum glucose follow-up after GDM in routine obstetric care is associated with both provider- and institution-related factors. Although obstetric healthcare professionals generally demonstrated good knowledge and positive professional beliefs, practice remained comparatively weaker. Specialised training, clinical experience, and institutional context were associated with implementation-related practice. Future efforts to strengthen training, optimise follow-up pathways, and improve institutional support may help reduce missed opportunities for postpartum follow-up and strengthen long-term diabetes prevention after GDM.

PMID:42630220 | PMC:PMC13493272 | DOI:10.3389/fendo.2026.1887259