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PubMed2026

Impact of real-time respiratory function monitoring on neonatal mask ventilation training: a multicentre simulation-based crossover study.

OBJECTIVE: To evaluate whether visibility of respiratory function monitor (RFM) feedback improves mask ventilation performance and influences subsequent ventilation performance during neonatal resuscitation training. DESIGN: multicentre randomised crossover simulation study. PARTICIPANTS: Healthcare professionals involved in neonatal resuscitation training across participating centres. INTERVENTION: Participants performed positive pressure ventilation (PPV) on both term and premature manikins under two conditions: with visible RFM feedback and with the display masked. The order of feedback visibility was randomised. Each participant completed ventilation assessments in both conditions. MAIN OUTCOME MEASURES: Primary outcomes were expired tidal volume (Vte) and mask leak (%). The proportion of breaths within the target Vte range (4-8 mL/kg) was calculated as a performance indicator. Secondary outcomes included variability in Vte and mask leak to assess ventilation stability between conditions. RESULTS: Visible RFM feedback was associated with lower mask leak and improved ventilation stability in the preterm manikin and with tidal volumes entering the target range in the term manikin. Participants initially ventilated with visible feedback maintained performance after feedback removal, suggesting a carry-over learning effect. CONCLUSION: In this multicentre crossover simulation study, visible RFM feedback was associated with changes in mask ventilation performance and evidence of a carry-over learning effect following feedback removal. Real-time visibility of respiratory parameters may strengthen neonatal resuscitation training.

Humans↗

PubMed2026

Psychotherapy training in psychiatry: a systematic review and narrative synthesis on the supervision experiences of early-career psychiatrists.

BACKGROUND: Supervision is a fundamental component of psychotherapy training, transforming theoretical knowledge into clinical skills through real-world practice. Psychotherapy training practices vary widely between countries, training programs, and over time, including supervision. Our systematic review aimed to investigate and describe the experiences of psychotherapy supervision through early-career psychiatrists' (ECPs) views. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and PubPsych for survey-based studies on ECPs' experiences of psychotherapy supervision during or after their psychiatry training and reported our findings according to the PRISMA guidelines. Of 32,877 articles screened, 29 articles were included. Each article underwent quality assessment, and results were synthesized narratively. RESULTS: Included articles published between 2000 and 2025, were from Europe (N = 16, 55.1%), the Americas (N = 5, 17.2%), Western Pacific (N = 4, 13.7%), South-East Asia (N = 2, 7%), Eastern Mediterranean (N = 1, 3.5%), and Africa (N = 1, 3.5%), with a total of 4691 participants. Supervision access rates ranged from 26.2% in Nigeria to 85.5% in Russia, with significant variation across countries and psychotherapy modalities. Most ECPs received 50-100 total hours of supervision, frequently delivered in weekly sessions. While formats, individual, group, or mixed, varied by country and training scheme, supervision was generally provided by a psychiatrist-psychotherapist. Common learning techniques included oral consultations and case discussions, followed by audio recordings or transcripts. The need to self-fund psychotherapy supervision costs was identified as a prominent barrier. CONCLUSIONS: Psychotherapy supervision is inconsistent globally, with barriers including supervisor availability and cost. There is a large implementation gap between recommendations and evaluated practice. Digital tools and competency-based frameworks may improve access and quality.

Humans↗

PubMed2026

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

PubMed2026

Ecr positively regulates activity of the PhoQ/PhoP signalling system in Klebsiella pneumoniae.

BACKGROUND: The rising prevalence of polymyxin resistance in multidrug-resistant Klebsiella pneumoniae presents a critical situation with limited therapeutic options. METHODS: Methods Genomic sequencing of 15 clinical polymyxin-resistant K. pneumoniae strains with multidrug resistance revealed that MgrB inactivation, predominantly disrupted by insertion sequences (ISs) in the IS1, IS4, and IS5 families, was the leading cause of polymyxin resistance. Comparative transcriptomics of wild-type, ΔmgrB, and ΔmgrBΔphoP were performed to elucidate the MgrB-PhoPQ regulatory network. RESULTS: This study conducted a system-wide analysis of the regulatory network and identified a species-specific PhoPQ regulon in K. pneumoniae.Beyond the classical MgrB-PhoPQ-ArnBCADTEF pathway, we identified a previously unannotated PhoPQ-regulated gene, 144 bp LN739_RS09850, encoding an Ecr homologue from Enterobacter cloacae. This protein has been reported to confer colistin heteroresistance, with the underlying mechanism not yet functionally validated. This study revealed that overexpression of Ecr homologues decreased colistin susceptibility in both K. pneumoniae and E. cloacae, but this phenotype was abolished upon phoP deletion, confirming PhoP's essential role. Consistent with this dependency, comparative transcriptomics of Ecr-overexpressing K. pneumoniae vs. control revealed significant upregulation of mgrB, phoPQ, arnBCADTE, and pmrD. Two-hybrid bacterial assays further demonstrated direct Ecr-PhoQ interaction. Electrophoretic mobility shift assay confirmed that PhoP directly binds to the ecr promoter in vitro, and a β-galactosidase reporter assay demonstrated that PhoP enhanced ecr promoter activity, indicating that PhoP regulates ecr expression by directly controlling its transcription. CONCLUSION: Collectively, these findings suggest that PhoP may directly activate the transcription of Ecr, with Ecr feedback activating the PhoPQ system via interaction with PhoQ, leading to induction of the arn operon and consequent polymyxin resistance.

Klebsiella pneumoniae↗

PubMed2026

Psychological skills training for sport-related outcomes: An umbrella review of evidence credibility and methodological quality.

Psychological skills training (PST) is widely used in sport, but review-level evidence remains fragmented across interventions, populations, outcomes, and methodological standards. This umbrella review synthesized evidence on PST-related interventions for sport-related outcomes, including athletic performance, psychological outcomes, cognitive performance, and sports injury, and evaluated evidence credibility, certainty, and methodological quality. A systematic literature search was conducted on 21 May 2025 in MEDLINE, PsycInfo, PubMed, Scopus, SportDiscus, Web of Science, and CINAHL Complete. Overall, 61 reviews involving 42,106 participants were included; 35 meta-analyses involving 28,076 participants were eligible for quantitative synthesis, and 26 reviews or meta-analyses involving 14,030 participants were summarized qualitatively. Quantitative findings showed generally positive point estimates for mindfulness-based interventions, imagery practice, music-based interventions, neurofeedback, perceptual-cognitive training, and multiple PST interventions, but most findings were weak or non-significant and certainty was generally very low. Qualitative evidence suggested potential benefits, but conclusions varied according to intervention definition, delivery, outcome measurement, and methodological quality. Evidence was more developed for athletic performance and psychological outcomes than for cognitive performance and sports injury. Overall, PST-related interventions may benefit sport-related outcomes, but conclusions should remain cautious because of low certainty, methodological heterogeneity, and limited evidence credibility.

Humans↗

PubMed2026

A Randomized Clinical Trial to Compare Moxifloxacin Versus Azithromycin for the Treatment of Mycoplasma genitalium: The FARTHEST Study.

BACKGROUND: Mycoplasma genitalium (MG) is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. International guidelines recommend resistance-guided therapy; however, access to genotypic testing is limited, and randomized trial evidence is lacking. We assessed the efficacy of moxifloxacin and azithromycin without resistance assays. METHODS: This monocentric, open-label, superiority, randomized controlled trial enrolled adults with MG infection detected by multiplex PCR, randomized 1:1 to receive moxifloxacin 400 mg daily for 10 days or azithromycin 500 mg daily for 6 days. A test of cure was performed ≥28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations. Subgroup analyses assessed symptomatic versus asymptomatic infections, doxycycline exposure, re-treatment, and sexual behavior. RESULTS: Among 358 randomized participants, 87.0% of those treated with moxifloxacin and 61.2% of those treated with azithromycin achieved microbiological cure in the ITT analysis (absolute risk difference 25.8%, 95% CI 16.5, 35.2). The superiority of moxifloxacin was confirmed in the ITT and PP populations. Moxifloxacin remained superior across most subgroups, whereas azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only one case of discontinuation. CONCLUSIONS: Moxifloxacin demonstrated superior efficacy compared to azithromycin for treating MG infection in the absence of resistance testing. These randomized data support the use of moxifloxacin as a first-line option when resistance assays are unavailable and may inform treatment strategies.

Humans↗

PubMed2026

Genomic and One Health insights into Vibrio parahaemolyticus from environmental, seafood and clinical sources.

Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis worldwide, with climate warming facilitating its spread to high-latitude areas. In this study, we analyzed 212 genomes of environmental and seafood-associated isolates collected from seven cities in Zhejiang Province, China (2019-2024), alongside 228 clinical genomes from public databases. The 212 isolates were assigned to 172 sequence types (STs), with ST490 being the most frequent (5/212, 2.36%). Forty-four serotypes were identified, dominated by OL3:KUT (12.68%). High ST and serotype diversity were observed across different sample types and sources, with median pairwise single nucleotide polymorphisms (SNPs) ranging from 57,431 to 58,378, indicating comparable genetic diversity across groups. All isolates carried tlh and T3SS1 but lacked tdh and T3SS2. Resistance rates against ampicillin and cefazolin were 54.72% (116/212) and 44.34% (94/212), respectively, with multidrug resistance (MDR) detected in nine isolates, predominantly from seafood (7/9). A total of 63 distinct antimicrobial resistance genes (ARGs) spanning seven classes were identified. Isolates from aquaculture farms and wet markets exhibited greater resistance category diversity and higher ARG carriage than those from coastal or riverine sites. In contrast, the 228 clinical isolates harbored only 25 ARGs across two classes, with a significantly lower proportion of isolates carrying multiple ARG classes (0.44% vs. 6.13%, P < 0.001). Human isolates formed tighter phylogenetic clusters, although a minority were closely related to environmental/foodborne strains. Overall, our findings demonstrate the genetic diversity and resistance potential of V. parahaemolyticus across environmental, seafood, and clinical sources, highlighting the importance of the One Health approach to comprehensive public health risk assessment.

Vibrio parahaemolyticus↗

PubMed2026

Structured Visualization for Laparoscopic Skill Acquisition:A Randomized Controlled Study.

OBJECTIVE: To evaluate whether structured visualization can support acquisition of basic laparoscopic skills during simulation training and whether this approach can achieve outcomes comparable to repeated physical practice. DESIGN: Prospective randomized comparative study. SETTING: Simulation-based laparoscopic skills training at a university-affiliated teaching center. PARTICIPANTS: Fifty laparoscopy-naive medical students were randomly assigned to a laparoscopic practice group or a visualization group. The laparoscopic practice group performed a validated Gynecological Endoscopic Surgical Education and Assessment (GESEA) Laparoscopic Skills Training and Testing (LASTT) hand-eye coordination task 7 consecutive times. The visualization group performed the same task physically on attempts 1, 4, and 7, while attempts 2, 3, 5, and 6 consisted of guided visualization. Each attempt lasted up to 2 minutes, and performance was scored as the number of correctly placed rings (range 0-12). RESULTS: Baseline performance was comparable between groups (2.92 ± 2.14 vs 2.88 ± 1.72; p = 0.94). Both groups improved significantly over time (p < 0.001). No statistically significant between-group differences were found on the 4th attempt (6.52 ± 3.25 vs 5.76 ± 2.57; p = 0.48) or 7th attempt (8.24 ± 2.86 vs 7.44 ± 2.99; p = 0.39). The final physical performance of the visualization group was significantly better than the 3rd physical attempt of the laparoscopic practice group (p = 0.025). CONCLUSIONS: Structured visualization may support early laparoscopic skill acquisition and achieve short-term outcomes comparable to repeated hands-on simulator training. Visualization should be considered an adjunct, rather than a replacement, for physical practice in simulation-based laparoscopic education.

Laparoscopy↗

PubMed2026

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male↗

PubMed2026

Impaired toilet training and bladder and bowel dysfunction in children with developmental coordination disorder - an underreported issue.

BACKGROUND & OBJECTIVE: Children with Developmental Coordination Disorder (DCD) face significant, yet often overlooked, challenges beyond motor impairments, including difficulties with toilet training and bladder and bowel dysfunctions (BBD). This study aims to explore whether children with DCD exhibit greater difficulties in these areas compared to typically developing children (TDC). METHOD: This cross-sectional case-control study included 84 children aged 5-8 years (42 DCD, 42 TDC), matched by school-grade and sex (33 boys and 9 girls per group). Parents completed the Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) to assess BBD symptoms, the Dutch DCD-questionnaire (DCD-Q) to evaluate motor coordination, and additional questions regarding toilet training, elimination diagnosis, and co-occurring conditions. Correlations and exploratory group differences were analysed. RESULTS: Parents of children with DCD reported significantly more toilet training difficulties than parents of controls (p < 0.001), including persistent accidents (47.6% vs. 9.5%), prolonged training (45.2% vs. 4.8%), and difficulties recognizing urination urgency (40.5% vs. 2.4%). The parental report of delayed attainment of bowel and bladder control (p < 0.05) and BBD rates (p < 0.001) was also significantly higher in children with DCD. Exploratory analyses indicated that the prevalence of these outcomes was not significantly different between children with DCD with and without co-occurring ADHD or autism, suggesting a possible primary association with DCD. Additionally, across both children with DCD and TDC, poorer motor skills were associated with more BBD symptoms (r = -0.474, p < 0.001). CONCLUSION: Children with DCD have a higher prevalence of toilet training difficulties and BBD compared to TDC, potentially affecting their psychosocial well-being. Greater awareness is crucial for timely and targeted care. Notably, the study's design, directly comparing children diagnosed with DCD to matched TDC, provides new insights into the prevalence of elimination difficulties in this population.

Humans↗

PubMed2026

Effectiveness of passive vs. assistive robotic gait training on functional recovery and neuroplasticity post-stroke: A randomized controlled trial.

OBJECTIVE: This study seeks to compare the impacts of various robotic gait training (RAGT) modes on lower limb motor function recovery in stroke patients while exploring the corresponding neural mechanisms. DESIGN: A single-blind, randomized controlled trial. SETTING: Inpatient Rehabilitation Facility. PARTICIPANTS: Forty-eight patients aged 18-80 who had experienced their first unilateral subacute stroke accompanied by walking impairments were included. INTERVENTIONS: Participants were randomly assigned to: (1) assistive mode training, (2) passive mode training, or (3) control group receiving only traditional rehabilitation. Clinical and neurological outcomes were assessed at pre-intervention (T0), and post-2-week intervention (T1). MAIN OUTCOME MEASURES: Outcomes were evaluated using the Fugl-Meyer Assessment for Lower Extremity, Berg Balance Scale, Modified Barthel Index, the Functional Ambulatory Category, and functional near-infrared spectroscopy. RESULTS: Among the 48 patients recruited, significant time effects were observed across all groups in FMA-LE scores (p < 0.001). Notable improvements were detected in the conventional group (MD = 2.69, p＜0.01) and the passive group (MD = 3.67, p < 0.001), with the assistive mode also demonstrating a significant effect (MD = 1.79, p < 0.05). BBS scores improved across all groups; however, no significant differences were noted between the groups (p = 0.11). Similarly, MBI scores showed a significant time effect (p < 0.001), without notable group differences (p = 0.29). CONCLUSION: All training modalities effectively enhanced motor function, balance, and daily living skills in stroke patients. Distinct cortical activation and connectivity patterns were observed between training modalities, which may reflect different neuroplastic mechanisms. These preliminary neural differences may help inform personalized rehabilitation strategies, although no clinical superiority of one mode over another can be concluded from the present data.

Humans↗

PubMed2026

Effects of cold-water immersion after rugby-specific training on endurance performance.

BACKGROUND: This study investigated whether whole-body cold-water immersion (CWI) following rugby-specific training influences endurance exercise performance 24 h later. METHODS: Eleven healthy male collegiate rugby players completed an incremental cycling test to determine peak oxygen uptake (V̇O 2peak ) and time to exhaustion at baseline (Pre). One week later, participants performed a standardized rugby-specific training session consisting of warm-up, skill-based passing, contact drills, individual training (i.e., conversion kicking and scrummaging), and a bronco endurance test (total duration: 180 min), followed by one of two recovery interventions in a randomized order: 1) whole-body CWI for 8 min at 15 °C (CWI) or 2) seated rest for 8 min (Control). Participants then performed the incremental cycling test 24 h after each intervention. RESULTS: Training load during the rugby-specific training, assessed using heart rate-based training load and blood lactate concentrations, did not differ between the trials. Time to exhaustion (485±72 vs. 518±77 s, P=0.107, d=0.45) and V̇O 2peak did not differ between the Control and CWI trials, whereas the relative changes in these variables from Pre were greater in the CWI than in the Control trials (both P<0.05). Oxygen uptake, minute ventilation, and rating of perceived exertion during submaximal exercise were similar across the Pre, Control, and CWI trials. CONCLUSIONS: These results suggest that whole-body CWI following rugby-specific training may be associated with favorable changes in endurance exercise performance 24 h post-intervention compared with the control condition. However, the expectancy/placebo effect of water immersion on exercise performance could not be excluded.

Humans↗

PubMed2026

Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma.

BACKGROUND: Immunotherapy resistance in lung adenocarcinoma (LUAD) remains a critical clinical challenge, and the mechanisms underlying resistance-associated intratumoral heterogeneity are poorly characterized. METHODS: We performed single-cell RNA sequencing of LUAD patients receiving neoadjuvant immunotherapy (responders vs. non-responders), integrating inferCNV, GSVA, and differential expression analyses. Cluster-specific genes were validated across seven independent cohorts (TCGA-LUAD, GSE13213, GSE26939, GSE29016, GSE30219, GSE31210, GSE42127). A multi-algorithm machine learning framework was used to construct a prognostic model, and the immune microenvironment was characterized using TCIA scoring, seven infiltration algorithms, and ESTIMATE. ARNTL2 function was assessed by CCK-8 and Transwell assays in A549 and H1299 cells. RESULTS: Non-responders showed significant enrichment of epithelial cells, depletion of cytotoxic T/NK cells, and elevated copy number variation burden versus responders (p < 0.0001). A resistance-enriched malignant subcluster (Cluster 2) exhibited hyperproliferative and metabolic reprogramming signatures with upregulated KRT17, S100A2, and CST6, which showed tumor-specific overexpression, adverse prognostic value, and genomic amplification across cohorts. CoxBoost combined with survivalSVM achieved optimal predictive performance (C-index = 0.686), yielding robust risk stratification (HR: 2.54-10.51, all p < 0.05). Low-risk patients showed greater immune infiltration and higher TCIA immunophenoscores. ARNTL2 was an independent prognostic factor (HR: 2.07-4.64) strongly correlated with risk score (r = 0.69), and its knockdown suppressed proliferation and invasion in both LUAD cell lines (all p < 0.05). CONCLUSION: This study identifies a resistance-associated malignant subcluster in LUAD, constructs a validated CoxBoost + survivalSVM prognostic model with robust immune stratification, and establishes ARNTL2 as a core oncogenic driver and therapeutic target.

ARNTL2↗

PubMed2026

Evaluating the Effectiveness of an Intimate Partner Violence Training Intervention on Healthcare Providers' Preparedness, Knowledge, and Experiences: A Mixed-Methods Study From Nepal.

Intimate partner violence (IPV) places a considerable burden on health systems globally due to its profound effects on women's health, and women who experience violence often seek care from healthcare providers (HCPs). However, HCPs often lack the preparedness and confidence to respond effectively, resulting in missed opportunities for support and care. This study, conducted in Nepal, evaluated the impact of structured training intervention on HCPs' perceived preparedness, knowledge, and attitudes toward managing IPV and its mental health consequences, including self-harm and suicidal tendencies. The study was nested within a larger cluster randomized trial. A convergent mixed-methods design with a comparison group was conducted among 46 female HCPs in all public hospitals (except one) and 17 primary healthcare centers in Madhesh Province, Nepal. The intervention group (n = 24) received a 10-day intensive IPV and mental health training, while the control group (n = 22) completed 3-day training. Quantitative data were collected using a validated self-administered Physician's Readiness to Manage IPV questionnaire and IPV consequences scale. Paired and independent t-tests were applied to assess changes. Insights from key informant interviews were thematically analyzed to explore participant experiences and perceived impacts. At baseline, over 80% of participants had not received IPV management training. Post-intervention, significant improvements were observed in HCPs perceived preparedness (median change 2.1; 95% confidence interval (CI): 1.1- 2.9), knowledge (median change 2.7; 95% CI: 2.0-3.1), and awareness of IPV consequences (mean difference 1.2; 95% CI: 0.5-2.0), with greater gains in the intervention group. Qualitative findings revealed enhanced confidence in identifying IPV, addressing psychological impacts, and supporting survivors through safety planning and referral. The training significantly improved HCPs' knowledge, preparedness, and confidence to manage IPV and related mental health issues, underscoring the need to scale similar programs to frontline providers, particularly in rural and underserved settings, to strengthen health system's response to IPV.

Humans↗

PubMed2026

Characterization and application potential of two newly isolated phages targeting the prevalent multidrug resistant Salmonella serovars in China.

The escalating global threat of multidrug resistant (MDR) Salmonella, a foodborne pathogen with animal-derived foods serving as the primary transmission vehicle, underscores the urgent need for effective lytic phages for biocontrol. From 142 environmental and farm samples in Shandong Province, we isolated 103 phages active against MDR S. Enteritidis and S. Typhimurium, which were the most prevalent Salmonella serovars in China. Two Siphoviridae phages vB-SenS-S1 and vB-SenS-SEC2 were selected for further study. With optimal multiplicities of infection (MOIs) of 10-2 (vB-SenS-S1) and 10-5 (vB-SenS-SEC2), both phages exhibited a 20 min latent period, yielding burst sizes of 52 and 37 PFU/cell, respectively. They also demonstrated stability across a range of temperatures (50-60 °C), pH levels (5-11), and after 1 h of UV exposure. Genomic analysis identified vB-SenS-S1 (43,002 bp, 47.04% GC) and vB-SenS-SEC2 (42,948 bp, 47.65% GC) as novel double-stranded DNA phages. Functional annotation confirmed the presence of genes essential for structural assembly, host lysis, and DNA replication/metabolism, and also verified the absence of resistance, virulence, and lysogeny-associated genes. Both phages vB-SenS-S1 and vB-SenS-SEC2 exhibited synergy with colistin and tetracycline. The synergy with colistin was particularly potent, leading to complete bacterial eradication in vitro. The in vivo therapeutic efficacy was further validated in both Galleria mellonella larvae and murine models of MDR Salmonella infection. Combination therapy with vB-SenS-SEC2 and colistin not only dramatically increased survival but also achieved a significant reduction in bacterial burden across multiple visceral organs of infected mice. Moreover, vB-SenS-S1 (108 PFU/mL) completely inhibited MDR Salmonella on chicken meat at 4 °C and -20 °C when initial contamination was ≤103 CFU/mL. This study not only expands the diversity of Salmonella phages but also highlights their potential as biocontrol agents in both clinical veterinary use and food decontamination, thereby enhancing food quality and safety at both the meat production source and the terminal product.

Animals↗

PubMed2026

Real-world clinical utility of exome sequencing in pediatric drug-resistant epilepsy: Experience from a tertiary center in Thailand.

BACKGROUND: Genomic testing has increasingly contributed to the diagnosis and management of pediatric drug-resistant epilepsy (DRE), particularly in patients with suspected genetic etiologies. This study evaluated the diagnostic yield and real- world clinical utility of whole-exome sequencing (WES) in children with DRE. METHODS: Children with DRE and seizure onset before 15 years of age were enrolled between January 2020 and December 2023. Clinical data, including demographics, seizure characteristics, developmental history, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and prior investigations, were reviewed. WES was performed in all probands and, when available, their parents. Variants were interpreted according to standard guidelines. Clinical utility and 1-year seizure and developmental outcomes were assessed from follow-up records. RESULTS: Fifty-six patients (23 males, 33 females) were included. The median age at seizure onset was 1 year (interquartile range [IQR] 0.3-4 years), and 96.4% had developmental comorbidities. Pathogenic or likely pathogenic variants were identified in 39% (22/56), with the highest diagnostic yield in children with seizure onset before 3 years of age. Channelopathies accounted for most genetically solved cases (68%), predominantly involving sodium channel genes. Genetic diagnoses provided clinical utility in 73% (16/22) of solved cases by guiding treatment and precision management. At 1-year follow-up, genetically solved patients showed more favorable seizure and developmental outcomes than those with genetically unsolved patients. CONCLUSION: WES achieved a 39% diagnostic yield and substantial clinical utility in pediatric DRE, particularly in early-onset and channelopathy-related disorders. These findings support early molecular diagnosis to facilitate genotype-informed management in appropriately selected children. However, the more favorable developmental and seizure outcomes observed in genetically solved patients should be interpreted with caution, as they may have been influenced by multiple factors beyond genetic diagnosis. In resource-limited settings, careful clinical phenotyping remains essential for treatment decisions and for prioritizing children for genomic testing.

Clinical utility↗

PubMed2026

Cefiderocol susceptibility rates in carbapenem-resistant Gram-negative bacteria in a comparative, multicenter surveillance study in China.

BACKGROUND: Cefiderocol is a siderophore cephalosporin with potent, broad spectrum of activity against carbapenem-resistant (CR) Gram-negative bacteria. The objective of this surveillance study was to assess cefiderocol susceptibility in molecularly characterized CR Gram-negative pathogens collected from hospitalized patients across China. METHODS: Susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines, using pre-prepared frozen 96-well microtiter Thermo Fisher plates. Susceptibilities to cefiderocol and most comparators were determined by Clinical and Laboratory Standards Institute breakpoints, to tigecycline by US Food and Drug Administration breakpoints, and to colistin by European Committee on Antimicrobial Susceptibility Testing criteria. Carbapenemases were identified by whole-genome sequencing and polymerase chain reaction. RESULTS: Of 149 CR Klebsiella pneumoniae, 95.3% were susceptible to cefiderocol (OXA-48-positive 100% [n = 15]; IMP-positive 100% [n = 9]; KPC-positive 95.4% [n = 108]; NDM-positive 88.2% [n = 17]) and against 103 NDM-positive CR Escherichia coli, cefiderocol susceptibility was 45.6%. Among comparator antibiotics, ceftazidime-avibactam was only active against K. pneumoniae carbapenemase-positive and OXA-48-positive K. pneumoniae isolates. Susceptibilities to tigecycline and colistin were between 22.2% and 97.1% and between 88.2% and 100% across CR Enterobacterales with different carbapenemases, respectively. High cefiderocol susceptibility rates were found for CR Pseudomonas aeruginosa (98.4%), CR Acinetobacter baumannii (99.6%), and Stenotrophomonas maltophilia (99.6%). Among comparator antibiotics, only colistin showed high activity against CR P. aeruginosa (99.2%) and CR A. baumannii (99.2%). CONCLUSIONS: Cefiderocol susceptibility rates were ≥88% against a collection of carbapenemase-positive CR Gram-negative isolates, except for lower susceptibility in NDM-positive CR E. coli isolates. Continuous monitoring of cefiderocol susceptibility is warranted.

Cefiderocol↗

PubMed2026

Proficiency-based training and evidence-based methodology: a systematic review and meta-analysis.

OBJECTIVE: To assess adherence of self-labelled proficiency-based progression (PBP) studies to evidence-based PBP criteria and examine associations with training outcomes. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews. PubMed, CENTRAL, EMBASE, MEDLINE, and Scopus were searched from inception to 1 March 2023. Prospective English-language studies on healthcare procedural training reporting objective performance outcomes were included; non-prospective, non-quantitative, non-procedural, non-English studies, and reviews were excluded. Pre-specified outcomes included adherence to 18 evidence-based PBP criteria and objective performance metrics (errors, steps, time); secondary outcomes included proficiency benchmark achievement and Likert ratings. Data extraction was performed independently by multiple reviewers. Study quality was assessed using the Medical Education Research Study Quality Instrument and risk of bias by two investigators. Effect sizes were pooled using random-effects models (DerSimonian-Laird), expressed as the ratio of means (ROM) for continuous outcomes and bias-corrected odds ratios for dichotomous outcomes. RESULTS: Of 646 studies identified 175 met inclusion criteria. In the PBP studies (n = 18), 94% fulfilled minimum criteria (use of a proficiency benchmark, its quantitative definition, and requirement for demonstration prior to progression) vs 36% of non-PBP studies (n = 157). If all PBP criteria were included, 83% of PBP studies used these criteria vs only 2% of non-PBP-studies. In quantitative analysis (27 randomised clinical studies, 761 participants), ROM results showed that PBP training reduced the number of performance errors by 58% (P < 0.001) and procedural time by 28% (P = 0.006), increasing number of steps performed by 22% (P = 0.03). When stratified based on number of criteria fulfilled, meta-regression demonstrated that increasing the number of PBP criteria fulfilled was associated with progressive and systematic trainee performance improvement. CONCLUSIONS: The more training methodologies adhere to established PBP criteria, the better training outcome will be.

Humans↗