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Effects of feeding different baits on the growth of Scylla paramamosain megalopa and the bacterial community in a mariculture system

Diagnostic yield of exome sequencing in nonobstructive azoospermia (NOA): A systematic review and meta-analysis

Azoospermia is considered as the most severe form of male infertility. The application value of exome sequencing (ES) in males with non-obstructive azoospermia (NOA) remains unclear. This study aims to review the known genetic causes of NOA and evaluate the diagnostic yield of ES in males diagnosed with idiopathic NOA. We performed a systematic database search in Ovid MEDLINE, EMBASE, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from database inception to March 2025. Two independent reviewers assessed the literature and included those studies investigating the utility of ES testing in men diagnosed with NOA and fulfilling the eligibility criteria. The pooled diagnostic yield was calculated using single-proportion analysis with random–effects modeling, and confidence intervals (CI) were estimated using the Clopper–Pearson exact method. A total of nine studies were included, and the qualities were assessed to be moderate to high via the modified STARD. Among the cohorts analyzed (nine studies comprising 1,728 individuals with NOA), the overall diagnostic yield of ES testing was 15% (95% CI: 10%–20%; low-certainty evidence). Of the 270 positive cases identified through ES testing, mutations in 262 genes were detected, with AR, TEX11, FANCM, TDRD9, PNLDC1, M1AP, FBXO15, and DMRT1 being the most frequently observed. Among these cases, only 11.11% (5/45) reported successful testicular sperm extraction. The considerable heterogeneity indicates that the pooled prevalence estimates of the diagnostic yield of ES testing in NOA—approximately 15%—may overestimate the true diagnostic rate in the general NOA population. This estimate should thus be interpreted as an average across diverse clinical and methodological contexts, rather than a precise point estimate reflecting a uniform underlying effect. Future research, particularly large-scale studies using standardized protocols, is crucial to generate more accurate, reliable, and generalizable estimates of the diagnostic yield of ES testing in NOA.

An MILP approach for optimal operation of unbalanced distribution networks through coordinated network reconfiguration and SOP utilization

Phase II trial protocol of focal prostate ablation combined with androgen deprivation therapy for prostate cancer treatment

Background Prostate cancer (PCa) is one of the most commonly diagnosed cancers. Treatments for PCa with less adverse effects than whole gland interventions, such as focal therapy (FT), often involve a higher risk of PCa recurrence. Combining FT with other treatments could increase the efficacy while maintaining a low side effect profile. This study aims to determine the proportion of residual/recurrent clinically significant PCa following the combination treatment of three months of androgen deprivation therapy (ADT) and FT of the prostate, as well as the safety of this treatment regimen. Methods This study will be a single arm phase II trial with a recruitment goal of 57 patients with treatment naïve non-metastatic intermediate risk PCa. Patients will complete the I-PSS, SHIM, and EPIC-26 questionnaires at the screening visit. Patients will then comply with a three-month treatment course of ADT. Eight weeks after beginning ADT, patients will undergo FT of the prostate via high intensity focused ultrasound or cryoablation. Follow up visits will occur every three months for a year post FT to monitor for side effects, repeat questionnaires, perform a clinical assessment, and obtain PSA and testosterone values. Twelve months after FT, a surveillance multiparametric MRI and MRI-targeted biopsy will be performed to assess for treatment failure. Discussion The primary endpoint of this trial is to determine the proportion of men with clinically significant PCa as evaluated by a surveillance mpMRI and MRI-TB at 12-months following FT. If successful, this treatment approach could offer a new option for treatment with fewer side effects than whole gland interventions and more efficacy than FT alone. Furthermore it could inform the need for further research into multimodal treatment options for PCa. Clinical trial registration ClinicalTrials.gov, NCT05790213. Registered on March 30, 2023.

Multiscale tumor characterization in histopathology via self-distilled transformers and topology-aware visual encoding

Abstract The increasing complexity of whole slide images in histopathology requires models that would be accurate across magnifications while being robust to visual, topological, and contextual variations in the setting. Thus far, existing approaches have either failed to generalize across various resolutions, have ignored the inherent structural relationships within tissue architecture, or have not integrated a mechanism to adaptively prioritize samples during training. Aside from this, most approaches do not consider both pixel-level appearance and morphological context, which restricts their diagnostic reliability sets. This research aims to address these limitations by providing a framework for Multiscale Tumor Characterization by synergizing RepVGG-DINO encoders, self-distilled visual transformers, and hierarchical attentions. The Pathology-Adaptive Uncertainty-Aware Consistency (PAUAC) Framework ensures consistency in prediction across 10 and 40 and introduces a dual-branch consistency model with uncertainty-weighted KL divergence regularization. The Structural Attention-Constrained Graph Regularizer (SACGR) which is a topology-aware visual encoding technique focuses on constrains attention in the ViT decoders thereby embedding spatial priors from superpixel-based graphs into them. The Multiscale Pathology Curriculum Scheduler (MPCS) creates a sample prioritization mechanism based on entropy, guiding the training from simpler to more complex tissue patterns. The Transformer-Driven Dual-Modality Morphometry Network integrates H&E image features with Voronoi-based nuclear morphometry using cross-modal self-attention to enhance representational richness for the process. Finally, the Contrastive Cell-Contextual Representation Alignment (CCCRA) module improves embedding consistency across different magnifications by using positional contrastive learning sets. The combination of these modules brings measurable improvements (+2.3% Dice score, +21% faster convergence, +3.7% accuracy for morphologically ambiguous samples, and +12.6% normalized mutual information in embeddings) sets. This work marks a great leap in tumor characterization within histopathology, establishing resolution-aware, topology-constrained, and morphology-fused learning in an interpretable and scalable manner for the process.

Spatial autocorrelation and determinants of low uptake of breast cancer screening among women of reproductive age: A mixed-effect multilevel analysis of Tanzanian population-based survey

Introduction Breast cancer remains an important public health problem with high mortality in low-income countries like Tanzania. This is because of the low uptake of screening for breast cancer, an intervention that could be cost-effective and significant in reducing mortality and poor prognosis in such a setting. This is a population-based survey to uncover the spatial distribution and determinants of low uptake of breast cancer screening among women of reproductive age in Tanzania. Methods This analytical cross-sectional study utilized data from 2022 Tanzania Demographic and Health Survey and Malaria Indicator Survey (TDHS-MIS). A total of 15254 women aged 15–49 years were included in the analysis. The outcome variable was the uptake of breast cancer screening, coded as “1” for the women who reported a doctor or other healthcare provider examined their breasts to check for cancer, and “0” otherwise. Descriptive and geospatial analyses were conducted to assess patterns of screening uptake across regions. To identify associated factors, a mixed-effect multilevel logistic regression analysis was performed using Stata version 17. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported, and a significance level of p < 0.05 was used. Results The findings revealed that only 5% of the respondents reported having undergone breast cancer screening in Tanzania. The lowest uptake was in the Western (2.17%) and Southern (3.34%) zones of Tanzania. Regions with the poorest uptake of breast cancer screening were Kigoma (1.68%), Katavi (1.94%), Singida (1.54%), and Tabora (1.66%). Women with older ages, formal education, health insurance coverage, and reading newspapers, magazines, or using the internet had higher odds of uptake breast cancer screening than their counterparts. Conclusions The uptake of breast cancer screening remains low throughout Tanzania and worst situation was noted in rural areas. Formal education, insurance coverage, and access to information continue to propel the low uptake of breast cancer screening in Tanzania. The fair distribution of health-promotive services could be vital in increasing uptake of breast cancer screening for the early detection and prevention of mortalities and other outcomes related to this severe disease.

Modulating superconductivity in elementary materials by doping

SEANN: A domain-informed neural network for epidemiological insights

In epidemiology, traditional statistical methods such as logistic regression, linear regression, and other parametric models are commonly employed to investigate associations between predictors and health outcomes. However, non-parametric machine learning techniques, such as deep neural networks (DNNs), coupled with explainable AI (XAI) tools, offer new opportunities for this task. Despite their potential, these methods face challenges due to the limited availability of high-quality, high-quantity data in this field. To address these challenges, we introduce SEANN, a novel approach for informed DNNs that leverages a prevalent form of domain-specific knowledge: Pooled Effect Sizes (PES). PESs are commonly found in published Meta-Analysis studies, in different forms, and represent a quantitative form of a scientific consensus. By integrating PES into the training loss, we demonstrate—under controlled simulations—significant improvements in predictive generalization and in the epidemiological plausibility of the learned relationships, relative to a domain-knowledge agnostic neural network.

Fast and efficient intracellular delivery of large size nanoparticles into mammalian cells by in situ electroporation

The innate immune IMD pathway is a key regulator of gut microbiome and metabolic homeostasis in the black tiger shrimp (Penaeus monodon)

The gut microbiome plays a fundamental role in host health and homeostasis, yet immune mechanisms regulating this relationship remain poorly understood in commercially important invertebrate such as the black tiger shrimp ( Penaeus monodon ). We employed a multiomics approach, combining RNA interference (RNAi) with transcriptomic, metabolomic, and 16S rRNA gene profiling, to investigate how the innate immune Toll and IMD pathways regulate gut health. We systematically suppressed key signaling components, MyD88 (Toll) and Relish (IMD), under non-pathogenic conditions. Knockdown of the IMD pathway transcription factor, Relish , triggered a profound and selective response across all measured biological layers. We observed a disproportionately large transcriptomic change, with 1,362 differentially expressed genes (DEGs) in the Relish knockdown group compared to only 333 DEGs in the MyD88 knockdown group. This was accompanied by a targeted alteration in immune effectors, including the upregulation of lysozyme C-like (log 2 fold change = 2.44) and a strong suppression of penaeidin 5 (log 2 fold change = −3.62). At the microbial level, while overall community structure remained stable, a selective shift was observed, the abundance of specific Gram-negative genera, particularly Photobacterium and Shewanella , was significantly reduced, yet Pseudoalteromonas were enriched in the Relish knockdown group. Metabolomic analysis further revealed that the Relish -suppressed shrimp had a distinct metabolic signature, marked by a decrease in bacterial-associated metabolites like D-alanyl-D-alanine and an increase in pro-inflammatory markers such as succinic acid and 8-HETE. Our findings showed that in P. monodon , the IMD pathway is the primary and central regulator of gut microbiome and metabolic homeostasis. This study provides novel insights into the dynamic interplay between innate immunity and the gut microbiome in a crustacean, identifying the IMD pathway as a promising target for developing strategies to enhance shrimp health and the sustainability of the global aquaculture industry.

Characteristics of the meibomian gland in a population without dry eye symptoms

Carbon footprint comparison of video intubation tools: Disposable laryngoscopes, reusable laryngoscopes, and stylets

Purpose As healthcare systems grapple with their 5% global carbon footprint contribution, sustainable medical device selection emerges as a critical decarbonization lever. This life cycle assessment (LCA) quantifies environmental disparities among three prevalent video intubation tools—Disposable video laryngoscopes (VLs), reusable VLs, and video Stylets—to guide evidence-based procurement. Methods Using International Organization for Standardization (ISO)14040 compliant life cycle assessment (LCA) methodology—the international standard defining LCA principles and framework—we quantified cradle-to-grave emissions for three video intubation devices manufactured by Zhejiang UE Medical Corp. The functional unit (one tracheal intubation) incorporated material extraction, manufacturing, low-temperature LTPS/ HLD, transportation, and disposal. SimaPro 9.4.0 with Ecoinvent 3.8 database calculated CO₂ equivalents (kg CO₂e), validated through sensitivity analyses of sterilization loading (10–80 devices/cycle) and regional grids. Results The HLD-disinfected video stylet demonstrated superior environmental performance, emitting 98.24 kg CO₂e per 500 procedures—45.8% and 42.0% lower than reusable VLs (181.45 kg CO₂e) and disposable VLs (169.47 kg CO₂e), respectively. Sensitivity analyses identified sterilization loading as the dominant variable: half-load (50% chamber utilization) reduced emissions by 89–91% versus single-device processing, with full-load optimization yielding incremental 11–14% reductions. Process and regional variability further revealed that HLD decreased emissions by 19–24% compared to LTPS, while grid carbon intensity caused 24–33% variability (India vs. EU). Scenario comparisons confirmed the video stylet’s environmental dominance across sterilization methods—even with LTPS (349.99 kg CO₂e/500 uses), it maintained a 45% reduction over reusable VL baselines, whereas HLD-treated video stylets (94.32 kg CO₂e) showed 6.7-fold lower emissions than disposable VLs and 59% below HLD-reprocessed reusable VLs. Conclusions HLD-reprocessed video stylets are the environmentally optimal choice for high-volume, low-infection-risk settings. For low-throughput or high-risk scenarios, providers should balance environmental impacts with clinical requirements through frequency and resource assessment.

Gut microbiota profiling in Lebanese ulcerative colitis patients and healthy controls from a pilot study

Disruption of epidermal growth factor receptor signaling and cytoskeletal dynamics by mebendazole and gefitinib synergistically impairs paracrine cytokine signaling in non-small cell lung cancer and triple-negative breast cancer Cell lines

Background Aberrant paracrine cytokine signaling and dysregulated signal transduction are critical drivers of tumor progression and therapeutic resistance in aggressive cancers such as non-small cell lung cancer and triple-negative breast cancer. This study aimed to explore a dual-targeting strategy using mebendazole, a repurposed anti-parasitic agent known to disrupt microtubules, in combination with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor. The objective was to assess the combinatorial impact on cell viability and key regulatory pathways involved in inflammation, mitotic control, and nuclear transport. Methods Human lung adenocarcinoma (A549) and triple-negative breast cancer (MDA-MB-231) cell lines were treated with mebendazole, gefitinib, or a combination of both. Cell viability in both the cell lines was investigated using the MTT assay, while transcriptional profiling was conducted exclusively in the A549 NSCLC cell line to assess cytokine and regulatory gene modulation. Quantitative reverse transcription polymerase chain reaction was performed to evaluate changes in the expression of inflammatory cytokines (interleukin-1 beta, interleukin-6, TNF-alpha, IFN-gamma) and regulatory genes (MMP-2, STAT 4, RAN, and RCC1). Results Combined treatment with gefitinib (1 µM) and mebendazole (0.5 µM) elicited a pronounced synergistic cytotoxic response, reducing cell viability to ~8–10% in A549 and ~15% in MDA-MB-231 cells—representing an additional >50% and ~30–40% decrease, respectively, compared to the most effective single-agent treatment- gefitinib 1 µM. Gene expression analysis revealed significant downregulation of pro-inflammatory cytokines and alterations in genes involved in mitotic regulation and nuclear transport. These changes suggest impaired intracellular signaling and reduced tumor-supportive microenvironmental interactions. The dual approach disrupted both cytoskeletal architecture and receptor-mediated signal transduction, pointing to a multifaceted mechanism of action. Conclusions The combination of mebendazole and gefitinib effectively suppresses tumor cell viability and modulates key pathways involved in cancer progression. By targeting cytoskeletal integrity and EGFR signaling, it may disrupt cytokine and tumor–microenvironment interactions, supporting further exploration as a strategy to overcome resistance in lung and breast cancers.

Lower limb muscle synergies during deceleration at different change of direction angles

Safety of íntravitreal panitumumab combined with intravitreal ranibizumab in rabbits

Purpose To examine the safety of intravitreally applied epidermal growth factor (EGF) receptor antibody panitumumab combined with intravitreally injected vascular endothelial growth factor (VEGF) antibody ranibizumab in rabbits. Methods The experimental study included 8 male rabbits (age: 2−3 months; weight: 2.5–2.6 kg). The right eyes received three intravitreal injections of panitumumab (1 mg in 0.10 mL) combined with intravitreal injections of ranibizumab (0.5 mg in 0.05 mL) in intervals of 4 weeks, while the left eyes received three double intravitreal injections of Ringer´s solution (0.10 mL and 0.05mL). At baseline, at the time points of the re-injections, and at 2 weeks and at 6 weeks after the last injection, the animals were examined by fundus photography and optical coherence tomography (OCT). At study end at 2 weeks after the last injection for 4 animals (total study duration: 10 weeks) or at 6 weeks after the last injection for the remaining 4 rabbits (total study duration: 14 weeks), the animals were sacrificed and the eyes were histomorphometrically examined. Results The right eyes (study eyes) and left eyes (control eyes) did not differ significantly in cell count of the retinal ganglion cell layer (8.5 ± 8.3 cells per 150µm versus 4.5 ± 3.3 cells; P  = 0.04), inner nuclear layer (33.1 ± 14.0 cells versus 49.0 ± 22.3 cells; P  = 0.04) and outer nuclear layer (133.7 ± 50.0 cells versus 171.3 ± 75.3 cells; P  = 0.07) nor in mean thickness of the ganglion cell layer (31.8 ± 34.4µm versus 24.3 ± 15.2µm; P  = 0.15), inner plexiform layer (32.4 ± 48.2µm versus 25.6 ± 11.2µm; P  = 0.22), inner nuclear layer (26.6 ± 14.0µm versus 26.7 ± 10.2µm; P  = 0.43), outer plexiform layer (6.6 ± 3.7µm versus 6.8 ± 2.0µm; P  = 0.07), outer nuclear layer (32.6 ± 16.1µm versus 30.6 ± 11.8 µm; P  = 0.82) and of total retina (157.7 ± 99.4µm versus 152.0 ± 60.7µm; P  = 0.34). Apoptotic cells were not detected in either group. Mean IOP did not differ significantly between the right eyes (study eyes) and the left eyes (control eyes). Intravital signs of intraocular toxicity were not detected. Conclusions Repeatedly intraocularly applied panitumumab combined with ranibizumab was intraocularly well tolerated and did not differ in the ocular reaction from intravitreal injections of Ringer´s solution.

Manganese (III) meso-tetrakis(4-nitrophenyl) porphyrin sensitizes TiO₂ nanoparticles into visible region via a pyridyl linker for degradation of organic dyes

Optimizing the preparation of labeled N-glycans for rapid, simplified, and high-precision analysis

Glycan structures hold promise as biomarkers for the early detection of diseases, owing to their sensitive reflection of cellular states. However, glycan analysis remains complex and time-consuming, and the use of hazardous chemicals in traditional hydrazinolysis methods presents a significant barrier to broader application and cross-disciplinary research. To enable efficient glycan biomarker discovery, we aimed to develop a simple and accurate N -glycan analysis method capable of high-throughput sample processing. A key feature of this study is the use of pyridylamination, a fluorescent labeling technique that enables high isomer separation efficiency in reversed-phase LC/MS. After comparing various methods for N -glycan release and purification, we identified Rapid PNGase F (New England Biolabs) and BlotGlyco (Sumitomo Bakelite) as optimal for this application. To improve accuracy by reducing artifact formation, the BlotGlyco protocol was modified from the manufacturer’s original instructions. Using this optimized workflow, we successfully analyzed human serum, human urine, and CHO-K1 membrane fractions, demonstrating that distinct glycan structures in each sample type could be effectively separated and quantified. This work supports the broader adoption of glycan analysis across diverse research fields.

Automatic crack detection in civil infrastructure based on a hybrid fine tuned MnasNet and adaptive patching

Assessment of the impact of the new blister packaging of Biktarvy® (B/F/TAF) on treatment satisfaction of people living with HIV

Background Antiretroviral therapy (ART) is highly effective in people living with HIV (PLHIV), but its success depends on treatment satisfaction and adherence. A determinant of satisfaction regards how the medication is delivered to the patient, namely how it is contained (e.g., bottles, blisters, etc). A new packaging of Biktarvy ® has been introduced as a monthly blister, aiming to improve satisfaction, facilitate traceability of daily medication, portability, and discretion (reducing stigma associated with ART), and, ultimately, enhance adherence. Goals The study’s objective was to assess the impact of changing the packaging of Biktarvy® (B/F/TAF) from a standard pill bottle to a monthly blister with a weekly calendar on therapy satisfaction. Additionally, the association between treatment satisfaction and selected patients’ characteristics (e.g., ART duration) was evaluated. A secondary goal was to characterize the association between the change of packaging on patient’s adherence. Methods This is an observational longitudinal (retrospective and prospective) study with patients following ART for at least six months (ambulatory clinical management) recruited according to a non-probabilistic sequential sampling. Satisfaction was measured at two different moments: at baseline, HIVTSQs were used to assess satisfaction within the previous six months’ use of medication containers (bottles). Six months later, patients filled in the HIVTSQc to assess their perception of satisfaction change with the new packaging (blister). Adherence was assessed by pharmacy medication dispensing at the hospital. Results The study enrolled 105 patients in two selected centers (102 patients completed the study). Patients were significantly more satisfied (HIVTSQc scores) with ART when using the new Biktarvy® blister pack package. Importantly, gains of ART satisfaction were higher among those less satisfied with the bottle packaging. No significant associations were found between HIVTSQc scores and sociodemographic or ART-related variables.