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5-Fluorouracil modulates motility and biofilm-associated gene expression in Pseudomonas aeruginosa
Pseudomonas aeruginosa is an opportunistic pathogen in which motility, biofilm formation, and stress adaptation contribute to virulence. Drug repurposing represents a practical strategy for identifying compounds that influence these processes. In this study, the effects of 5-fluorouracil (5-FU) on motility, extracellular DNA (eDNA) production, and gene expression were examined in P. aeruginosa PAO1. Swimming, swarming, and twitching motility assays were performed in the presence of increasing concentrations of 5-FU. Transcriptional responses of motility, rhamnolipid, and DNA repair-associated genes were evaluated using quantitative real-time PCR. eDNA levels were quantified using fluorescence-based assays and visualized by confocal laser scanning microscopy. Exposure to 5-FU resulted in concentration-dependent reductions in swimming, swarming, and twitching motility. These changes were associated with downregulation of multiple genes involved in flagellar and type IV pili function, including motA , flhA , fliD , pilA , and pilI , and reduced expression of lasB and rhlAB . At 24 h, eDNA levels were decreased relative to untreated controls, whereas at 48 h, higher concentrations of 5-FU were associated with increased eDNA accumulation and upregulation of several DNA repair genes, including xthA , nth , recJ , sbcB , and eddB . These results indicate the multifaceted effects of 5-FU on important virulence factors of P. aeruginosa.
Counting missing babies in Tanzania: Neonatal mortality data quality from Tanzania’s District Health Information System across 28 Regional and 7 Tertiary hospitals (2015–2024)
Introduction The Sustainable Development Goal 3.2 targets reducing the neonatal mortality rate (NMR) to <12 per 1,000 live births by 2030; however, 65 countries, including Tanzania, remain off track. The 2022/23 Tanzania Demographic and Health Survey (TDHS) reported an NMR of 24 per 1,000 live births, equivalent to 48,000 neonatal deaths annually. Methods Neonatal deaths were extracted from the District Health Information System (DHIS2) for 28 Regional Referral Hospitals (RRHs) and seven tertiary hospitals from 2015 to 2024. Data quality was assessed by: (1) completeness, as the proportion of months each hospital reported neonatal deaths; (2) internal consistency, comparing mean NMR for 2021–2023 with 2024 following WHO guidance; and (3) external plausibility, comparing DHIS2 with DHS and UN estimates. For seven hospitals implementing NEST360 program, NMRs from DHIS2 were compared with the Neonatal Inpatient Dataset (NID) for 2021 and 2024. Results Between 2015 and 2024, DHIS2 recorded an average of >8,500 neonatal deaths annually versus 48,000 expected. RRHs accounted for 30–40% of reported deaths, and tertiary hospitals for 4–11%. Overall monthly reporting completeness was 58.3%, higher in RRHs (median 61.7%, IQR 8.3–95.0%) than in tertiary hospitals (median 50%, IQR 0.8–73.3%), with only 8 RRHs (28.5%) and no tertiary hospital achieving >75% reporting. Only 28.6% of hospitals had internal consistency (NMR within ±33% of the mean) for 2021–2023. The DHIS2 NMR for 2024 was 5.9 per 1,000 (adjusted for ~20% home births), compared to 24 per 1,000 in DHS 2022/23. Compared with NEST360 NID, one tertiary hospital reported lower DHIS2 NMRs, and three RRHs reported higher (ratio >1). Conclusion Neonatal mortality reporting in Tanzania’s DHIS2 remains substantially under-captured, with notable variations across facilities. Although RRHs perform better than tertiary hospitals, overall data quality remains low. Improving reporting in underperforming facilities and leveraging high-performing RRHs can strengthen national neonatal mortality monitoring.
Evaluation of forage oat cultivars for alpine saline-alkaline environments: Trade-offs between yield, quality and stability
Oat cultivation in the alpine saline-alkaline Qaidam Basin requires cultivars that balance yield, quality, and stability. Identifying suitable cultivars is key to sustainable forage production. Three oat cultivars (‘Qinghai 444’, ‘Qingtian No. 1', and ‘Zhengshi No. 1’) were evaluated in a two-year (2024 and 2025) field trial. We measured agronomic traits, yield, photosynthetic parameters, and forage quality. Mixed linear models, correlation analysis, and principal component analysis (PCA) were used to assess genotypic effects, environmental stability, and trait relationships. Cultivars exhibited distinct strategies. ‘Zhengshi No. 1’ achieved the highest fresh yield (3.29 and 1.96 t/ha) linked to greater stem diameter and photosynthetic rates but with high environmental sensitivity. ‘Qingtian No. 1’ provided stable, superior forage quality (highest crude protein: 11.44% and 10.33%). ‘Qinghai 444’ showed the most stable agronomic performance and highest water-use efficiency. Key trade-offs were identified, including a negative correlation between yield-related traits and forage quality (Relative Feed Value). The choice of optimal cultivar depends on primary goals: ‘Zhengshi No. 1’ for maximum biomass, ‘Qingtian No. 1’ for high quality, and ‘Qinghai 444’ for reliable performance under variable conditions. This provides an actionable framework for cultivar selection in saline-alkaline regions.
Video summarization based on multi-scale feature fusion
Video summarization aims to identify the important segments of a video and form a concise representation, enabling users to quickly grasp the core information. Existing graph-based video summarization methods suffer from insufficient modeling of multi-scale feature interactions and difficulties in balancing local and global features. To address this issue, this paper proposes a multi-scale feature fusion video summarization model based on the Message Passing Neural Network (MPNN) framework. First, the model extracts features of representative frames from video shots, and constructs a graph structure where shot features serve as nodes and inter-shot semantic similarity as edges. Second, it decouples the multi-scale features in the graph via the MPNN, and utilizes the Graph Attention Network (GAT) and Graph Neural Network (GNN) to extract local correlation features and global features, respectively. Finally, it fuses the original shot features, local features and global features as the final features to calculate shot importance and generate the video summary. On SumMe (F1 = 50.0) and TVSum (F1 = 61.8) datasets, MSF-MPNN achieves competitive performance against mainstream RNN/GNN-based methods. MSF-MPNN provides a practical solution for efficient video content extraction, with potential in video surveillance and short-video platforms.
Dose-response relationships of sensorimotor-based interventions on balance performance in older adults: A systematic review and meta-regression analysis
Falls are a severe public health challenge for older adults. Although sensorimotor-based interventions can remodel balance, their quantitative dose-response trajectories remain unknown, often leading to blindly accumulated doses. We aimed to identify optimal intervention strategies by deconstructing these non-linear dynamics. A comprehensive search of five databases up to February 2026 identified relevant randomized controlled trials (RCTs). We constructed a random-effects model using the standardized mean difference (Hedges’ g). Restricted cubic spline (RCS) and meta-regression models explored the non-linear dynamics of total intervention dose and the moderating effects of age. We included 24 studies comprising 1,110 participants. Sensorimotor-based interventions significantly improved dynamic balance (Timed Up and Go Test [TUGT]: g = −0.89, Q = 78.19; low-certainty evidence), static balance (Berg Balance Scale [BBS]: g = 0.94, Q = 21.14; high-certainty evidence), and neuromuscular control, including Center of Pressure with eyes open (COP-EO: g = −0.66, Q = 8.19; low-certainty evidence) and Center of Pressure with eyes closed (COP-EC: g = −0.34, Q = 3.54; moderate-certainty evidence). The RCS model suggested significant non-linear dose dependency for dynamic balance (P non-linearity = 0.004), indicating a potential relative attenuation of effect sizes near a cumulative dose of 1000 minutes. Conversely, static balance showed no significant dose association. Increasing age significantly attenuated dynamic balance benefits (p = 0.047) but did not negatively affect static stability. The adaptive trajectories of dynamic and static balance responding to sensorimotor interventions diverge fundamentally. Based on these non-linear dose-response fluctuations and age-related characteristics, continuous time accumulation may not guarantee proportional linear returns. Optimizing fall prevention requires shifting toward precise interventions that consider dose-efficiency and age stratification rather than a “more is better” approach. Systematic Review Registration: INPLASY202630061.
Cardiorespiratory fitness profile of volunteer firefighters during intermittent incremental exercise: A cross-sectional study
Purpose We aimed to assess the physiological profile of male volunteer firefighters at a broad spectrum of exercise intensities to determine whether their cardiorespiratory fitness level is adequate to meet the physiological demands of their occupational activities. Methods Thirty-one male volunteer firefighters performed an intermittent incremental treadmill running exercise (with 4 min steps, 1 km·h −1 increments and 30 s rest periods). Cardiorespiratory variables were continuously monitored and blood lactate concentrations were obtained at baseline, throughout rest periods and post-exercise. The study followed a cross-sectional laboratory-based assessment, in accordance with the STROBE guidelines for cross-sectional studies. Results The increase in running velocity resulted in progressively higher values from low to severe exercise intensities in oxygen uptake (from 23.6 ± 7.5 to 44.1 ± 7.6 mL·kg −1 ·min −1 ; p < 0.001; η p 2 = 0.560), heart rate (from 133 ± 24 to 185 ± 14 bpm; p < 0.001; η p 2 = 0.459) and energy expenditure (from 127 ± 50 to 303 ± 51 kJ; p < 0.001; η p 2 = 0.654). Aerobic energy contributions progressively declined (94–83%), while anaerobic contributions increased (6–17%) across the incremental intensity domains. Inverse associations were reported between heart rate and body mass index at heavy (r = −0.38; p = 0.017) and severe (r = −0.34; p = 0.028) intensities, and with fat mass at heavy intensity (r = −0.32; p = 0.037). Conclusions Findings evidenced a moderate to strong effect of exercise intensities on most assessed variables, and approximately half of the participants (~52%) did not meet the age-specific oxygen uptake threshold recommended by widely referenced National Fire Protection Association (NFPA-USA) guidelines for performing their professional duties. Given the firefighters’ high physiological demands, they should follow structured training interventions and receive targeted nutritional guidance to improve their cardiorespiratory fitness while ensuring optimal performance in the field.
Identify perceived strategies for promoting happiness among nurses: Protocol for a mixed-methods study
Background Enjoyment at work and overall happiness are essential elements of a thriving workforce, particularly in high-pressure environments like healthcare. Nurses frequently experience occupational burnout and stress due to the demanding nature of their profession, which can adversely affect their performance, job satisfaction, and overall well-being. Understanding the factors that contribute to happiness in nursing is crucial, as fostering a positive work environment can lead to improved patient care, reduced turnover rates, and enhanced mental health among healthcare professionals. Objective This study aims to systematically investigate the current state of happiness among nurses in order to identify perceived strategies for enhancing their well-being. By employing a mixed-methods approach, we will gather quantitative data on happiness levels and qualitative insights into the experiences and perceptions of nurses regarding their work environment. The ultimate goal is to develop evidence-based recommendations that can be implemented within healthcare settings to promote happiness and mitigate the effects of burnout and stress, thereby contributing to a healthier and more productive workforce. Methods Utilizing a mixed-method protocol, the research consists of two distinct phases. The quantitative phase employs a two-stage sampling method to select participants from ten randomly chosen hospitals within a province, ensuring a representative sample. In the qualitative phase, snowball sampling will be utilized to achieve data saturation, allowing for a comprehensive understanding of the factors influencing happiness in nursing. Data collection will involve a range of instruments, including a demographic characteristics and occupational features checklist, the Oxford Happiness Questionnaire, and semi-structured interviews to gather in-depth insights. Data analysis will be conducted using SPSS-24 statistical software for quantitative data and MAXQDA for qualitative data, enabling a robust examination of the findings. Result The study is expected to yield a comprehensive understanding of the levels and determinants of happiness among nurses. Quantitative data will provide statistical insights into the prevalence of happiness and its correlation with demographic and occupational factors. Qualitative findings are anticipated to uncover nuanced perspectives on the challenges and enablers of workplace happiness, offering valuable context to the quantitative results. Together, these findings will inform actionable recommendations for fostering a supportive work environment in healthcare settings. Conclusions The anticipated outcomes of this study highlight the positive impact of workplace happiness on nurses’ health, job satisfaction, and overall quality of patient care. By identifying actionable perceived strategies to promote happiness in the workplace, this research aims to contribute to the development of supportive environments that enhance both staff well-being and patient outcomes. Ultimately, this study represents a vital step toward fostering a healthier, more engaged nursing workforce. Ethics approval IR.MAZUMS.IMAMHOSPITAL.REC.1402.119
Oil and gas drilling is shifting to the deep sea — here’s what is at stake
Lipid-modifying pharmacotherapy in diabetes mellitus: A protocol for a systematic review and network meta-analysis of randomised trials
Introduction The global prevalence of diabetes mellitus (DM) has risen markedly, with patients facing a substantially higher risk of atherosclerotic cardiovascular disease (ASCVD) and related mortality. Although lipid-modifying agents, including statins, fibrates, cholesterol absorption inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), bromodomain and extra-terminal motif inhibitors (BETi), and adenosine triphosphate-citrate lyase inhibitors (ACLi) continue to emerge, their comparative efficacy and safety in patients with DM remain uncertain. This study aims to address this gap through a comprehensive network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating cardiovascular outcomes, lipid-modifying efficacy, and safety among these therapies. Methods and analysis A systematic search will be performed in PubMed, Web of Science, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (via Ovid), International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov from inception, without language or regional restrictions. Eligible studies will include parallel-design RCTs comparing monotherapy or combination therapy. The primary outcome will be cardiovascular events (composite and individual), and secondary outcomes will include cardiac biomarkers, ASCVD risk scores, lipid parameters (TC, LDL-C, HDL-C, TG) and safety outcomes. Two reviewers will independently conduct study selection, data extraction, and quality assessment using the Cochrane Risk of Bias 2 (RoB 2.0) tool, with evidence certainty evaluated via the Confidence in Network Meta-Analysis (CINeMA) framework. Data will be standardized where appropriate, and analyses, including assessment of publication bias, will be conducted using Stata 18 and R. The protocol is registered with PROSPERO, and findings will be disseminated through peer-reviewed publication. Registration: PROSPERO CRD420251163974.
Safety profile of camrelizumab: An analysis based on literature and database review
Objective Real-world studies on the safety of camrelizumab are scarce. This study aimed to investigate the adverse drug reactions (ADRs) associated with camrelizumab and evaluate their clinical characteristics and management. Methods We retrieved data on ADRs related to the PD-1 inhibitor camrelizumab from the World Health Organization (WHO) adverse event reporting system database (VigiAccess) for the period from June,2019 to July 2025. Additionally, we conducted a retrospective analysis of case reports and case series on camrelizumab-related ADRs published from 2019 to 2025. Results 601 ADR reports were included in the VigiAccess database. Asian patients accounted for 99% (597/601), and the majority were male (69%). The most common classification of systemic organs (SOC) is hematological disorders (21.8%), skin reactions (14.3%), and systemic symptoms (8.8%). The main adverse reactions were: Hematological system: bone marrow suppression (10.3%), thrombocytopenia (5.1%); Skin: rash (5.7%), pruritus (4.3%), reactive capillary hyperplasia (RCCEP); systemic: fever (2.6%), chest pain (2.1%); serious events: myocarditis (1.2%), toxic epidermal necrolysis (TEN). Literature analysis included 80 patients (from China), with a median age of 60 years (range 20–84), and 72.5% were male. The main indications are non-small cell lung cancer (20%), nasopharyngeal carcinoma (20%) and hepatocellular carcinoma (11.3%). The median occurrence time of adverse reactions was 8 weeks (ranging from 10 minutes to 88 weeks). Typical ADRs include: cutaneous toxicity (45 cases, 56.3%); RCCEP (32 cases), Stevens-Johnson (SJS)/TEN (5 cases); hematological toxicity (38 cases, 47.5%): bone marrow suppression (22 cases), thrombocytopenia (16 cases); cardiotoxicity (13 cases, 16.25%), mainly myocarditis; Others: immune hepatitis (6 cases), thyroid dysfunction (5 cases). Conclusion The ADRs of camrelizumab are primarily hematologic and skin toxicities, with a need to be vigilant for late-onset serious events (e.g., myocarditis, TEN). Early identification and corticosteroid intervention are key management strategies.
Integrated experimental and computational characterization of bioactive metabolites from Streptomyces paradoxus GH53 with antimicrobial, antioxidant, and antitumor activities
Abstract Streptomyces species are widely recognized as valuable sources of secondary metabolites with diverse biological activities. In this study, the isolate GH53 was identified as Streptomyces paradoxus based on morphological characteristics and partial 16 S rRNA gene sequence analysis. Fermentation conditions were optimized to enhance metabolite production, and the crude ethyl acetate extract was chemically characterized using GC-MS, FT-IR, and UV-Vis spectroscopy. The analytical profile suggested the presence of a chemically complex mixture containing fatty acids, fatty acid derivatives, hydrocarbons, and terpenoid-related constituents. The IC₅₀ values of the crude extract were 0.175 ± 0.013 and 0.097 ± 0.006 mg/mL for the DPPH and ABTS radical scavenging assays, respectively. Because the calculated DPPH IC₅₀ value was slightly below the lowest tested concentration, it should be interpreted as a fitted estimate derived from the dose–response curve rather than as a directly measured concentration point. It also showed cytotoxic activity against HePG-2 and MCF-7 cell lines, with IC₅₀ values of 19.50 ± 1.5 and 28.81 ± 2.0 µg/mL, respectively. To provide a preliminary molecular interpretation of these extract-level bioactivities, selected representative metabolites tentatively identified by GC-MS were evaluated individually as defined ligands using molecular docking, molecular dynamics simulation, and ADMET prediction. The modeled compounds showed favorable predicted interactions with selected antimicrobial-, antioxidant-, and anticancer-related protein targets, and the corresponding protein–ligand complexes generally maintained stable interaction profiles during simulation. However, ADMET analysis indicated potential limitations for some high-molecular-weight lipophilic constituents, including poor drug-likeness, limited predicted solubility, and possible toxicity liabilities. Overall, these findings suggest that S. paradoxus GH53 represents a promising source of bioactive metabolites for future fractionation, purification, structural confirmation, and compound-level biological evaluation. The results should be interpreted as preliminary screening evidence and not as confirmation of therapeutic efficacy or direct systemic drug suitability.
Integrative group psychotherapy reduces daily cortisol output and hair cortisol: A randomized active‑controlled trial with multi‑day profiling
Background Chronic psychosocial stress can disrupt hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system function, yet randomized trials rarely combine multi-day diurnal salivary profiling with hair glucocorticoid assessment. Methods We conducted a parallel-group, superiority randomized controlled trial with 1:1 allocation to compare an 8-week integrative group program with a dose-matched active control. The intervention combined social-affective skills training, slow breathing with heart-rate-variability biofeedback, and cognitive reappraisal. The primary outcome was the change from baseline (T0) to end of treatment (T1) in daily salivary cortisol output, measured as the area under the curve with respect to ground (AUCg) from 3-day profiles. Key secondary outcomes were the cortisol awakening response, diurnal cortisol slope, salivary cortisone AUCg, salivary alpha-amylase AUCg, and hair cortisol concentration assessed from proximal 1-cm hair segments collected at the end of treatment and at the 6-month follow-up visit, with each segment indexing approximately the month immediately preceding collection. Outcomes were analyzed using intention-to-treat mixed-effects models with false-discovery-rate correction for secondary outcome families. Results Sixty participants were randomized to the intervention group (n = 30) or the control group (n = 30). The intervention reduced daily cortisol AUCg more than control from T0 to T1 (between-group difference in change, −21.91 nmol/L·h; 95% CI, −25.87 to −17.95), and this reduction was maintained at T2. Salivary cortisone AUCg and salivary alpha-amylase AUCg also decreased more in the intervention group. Hair cortisol concentration was lower in the proximal 1-cm segments collected at the end of treatment and at the 6-month follow-up visit. Trier Social Stress Test peak cortisol and baseline-corrected AUCi reactivity within the collected −1 to +30 min window did not differ significantly between groups. Adverse events were infrequent and similar between groups. Limitations The trial was conducted at a single site, and the Trier Social Stress Test subsample was modest. Conclusions An 8-week multicomponent group program reduced daily HPA-axis output and proximal-segment hair cortisol under active-control conditions. Trial registration ClinicalTrials.gov NCT06863948 (registered 07 Mar 2025).
An interviewer–evaluator–judger LLM framework for text-based personality inference
Seven ways endurance sports have taught me to be a better researcher
HF-OCAQ: Oral comfort assessment in heart failure patients
Oral discomfort is common among patients with heart failure (HF), with the potential to compromise nutritional intake, communication, and health-related quality of life. Existing oral assessment tools are predominantly clinician-administered and focused on objective pathology, thus failing to adequately capture patients’ subjective experiences of oral comfort. A patient-reported instrument specifically designed for HF populations is lacking. To develop and preliminarily validate a novel PROM, the HF Patients’ Oral Comfort Assessment Questionnaire (HF-OCAQ), designed to multidimensionally assess perceived oral comfort in hospitalized patients with HF. An initial item pool was generated through literature review, qualitative patient interviews, and expert consultation, guided by Kolcaba’s Comfort Theory. Content validity was evaluated using a two-round Delphi process. A pretest was conducted to assess feasibility and clarity. The questionnaire was then administered to hospitalized patients with HF from three general hospitals between June and September 2020. Psychometric comprised assessments of content validity indices, internal consistency reliability, criterion-related validity against the Beck Oral Assessment Scale (BOAS) using Pearson’s correlation, and structural validity via exploratory factor analysis (EFA) using a common-factor model. A total of 190 valid questionnaires were included in the final analysis. The final HF-OCAQ consisted of 24 items. Content validity indices were high (I-CVI range: 0.833–1.000; S-CVI/UA: 0.875; S-CVI/Ave: 0.979). Internal consistency was acceptable (Cronbach’s α = 0.810). Criterion-related validity showed a weak but statistically significant correlation with BOAS scores (r = 0.233, p < 0.05), consistent with the conceptual distinction between subjective comfort and objective oral status. Exploratory factor analysis supported a four-factor structure that was theoretically coherent and aligned with the proposed multidimensional construct of oral comfort. The HF-OCAQ was developed and preliminarily validated as a patient-reported instrument for assessing perceived oral comfort in hospitalized patients with HF. The findings provide initial evidence supporting its content validity, internal consistency, and structural validity. Further studies, including confirmatory factor analysis, test–retest reliability, and assessment of responsiveness to clinical change, are warranted before broader clinical and research application.
Association of the sulfur microbial diet with metabolic profile, gut-related biomarkers, and adiposity indicators in adults with overweight and obesity
Are boldness and belligerence related?
Teosinte alleles enhance nitrogen assimilation and seed protein in maize
An energy- aware algorithm for optimizing dynamic zone monitoring and multiple cluster head selection with routing in border surveillance WSNs
Border surveillance plays a vital role in national security, necessitating the deployment of efficient and strong Wireless Sensor Networks (WSNs) to reveal and protect sensitive areas. This research describes a unique approach for optimizing border surveillance that combines a hybrid energy efficient zone-based dynamic clustering method with routing utilizing Geometric Modified Ant colony Harris Hawk Optimization Algorithm (EECR-GeMACHHOA). Our proposed method aims to enhance energy efficiency and prolong the network lifespan. This technique starts with the identification of zone monitors using geometric translational symmetry capabilities, which enables the formation of zones. These zones are then optimized by making use of modified ant colony based on dynamic pheromone evaporation for multiple cluster head selection. The EECR-GeMACHHOA improves routing pathways by integrating geometric, nature-inspired Ant colony and Harris Hawk optimization methodologies in order to decrease energy utilization and maximize the packet transmission rate. The proposed approach reduces network latency by 6.66%, consumes 15.03% less energy, and sends 9.86% increase in packets sent to the base station relative to alternative methods. The outcomes demonstrate a very good increase in network lifetime, robust energy efficient system, and data packet transmission dependability when compared to contemporary strategies.