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Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals

Premenarche risk factors for future dysmenorrhoea: a prospective cohort study.

BACKGROUND: Dysmenorrhoea, or pain during menstruation, is common in adolescence and is often dismissed or left untreated. Dysmenorrhoea can interfere with daily functioning and can lead to other chronic pain conditions; however, little is known about the risk factors for dysmenorrhoea. We aimed to characterise premenarche risk factors for the presence and severity of future dysmenorrhoea. METHODS: In this prospective cohort study, we obtained data for female adolescents from the population-based Adolescent Brain Cognitive Development Study (USA) who were premenarchal at baseline (age 9-10 years) and had both reached menarche and completed the Menstrual Cycle Survey at 3-year follow-up (age 12-13 years). Parents or guardians provided sociodemographic information and completed the Child Behavior Checklist, the Sleep Disturbance Scale for Children, and the Pubertal Development Scale, which captured data on non-painful somatic symptoms, attention problems, anxiety, depression, sleep disturbances, and pubertal development at baseline. Our primary objective was to analyse associations between dysmenorrhoea at 3-year follow-up (status and severity) with select symptom domains (sleep problems, attention problems, somatic symptoms, anxious or depressive symptoms, and baseline pain status) at baseline. We also investigated associations between dysmenorrhoea and participant characteristics (pubertal status, race or ethnicity, and income-to-needs ratio) that underlie social determinants of health. Differences by race were tested using Fisher exact tests. Differences by ethnicity and baseline pain status were tested using &#x3c7;2 tests. Differences in continuous variables were assessed using ANOVA. Wilcoxon-Rank Sum tests were used in analyses of sleep problems, attention problems, and somatic symptoms, and ANOVA was used for pubertal status and income-to-needs ratio. Multinomial logistic regression was used to test associations with dysmenorrhoea severity, and linear regression was used to test associations with dysmenorrhoea status and menstrual pain interference. FINDINGS: 2254 female adolescents were included in this study. 1299 (57&#xb7;6%) participants developed dysmenorrhoea at age 12-13 years, and 247 (19&#xb7;0% of those with dysmenorrhoea) reported severe dysmenorrhoea. Non-painful somatic symptoms were prospectively associated with future dysmenorrhoea (odds ratio [OR] 1&#xb7;17 [95% CI 1&#xb7;04-1&#xb7;32]; p=0&#xb7;0070), whereas anxiety or depression, sleep disturbances, and attention problems were not. Sleep disturbances were prospectively associated with menstrual pain interference (&#x3b2; coefficient 0&#xb7;16 [95% CI 0&#xb7;01-0&#xb7;31]). Advanced pubertal status at ages 9-10 years was prospectively associated with risk of dysmenorrhoea 3 years later (OR 1&#xb7;79 [95% CI 1&#xb7;47-2&#xb7;17]; p<0&#xb7;0001), as was lower income-to-needs ratio (0&#xb7;96 [0&#xb7;93-1&#xb7;00]; p=0&#xb7;031). Black (1&#xb7;38 [1&#xb7;05-1&#xb7;83]; p=0&#xb7;024) and Hispanic (1&#xb7;34 [1&#xb7;03-1&#xb7;68]; p=0&#xb7;010) young females were at a significantly greater risk of experiencing dysmenorrhoea than were White and non-Hispanic young females, respectively. INTERPRETATION: Sociodemographic characteristics and clinical symptoms present before menarche might help to identify at-risk individuals for dysmenorrhoea before pain becomes a lifelong issue. FUNDING: The National Institute of Nursing Research, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Eunice Kennedy Shriver National Institute for Child Health and Human Development.

Humans

Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resources limit routine monitoring of all patients, trauma care remains largely symptom-driven. The combination of long-term disability and limited capacity for routine follow-up highlights the need for risk-stratified follow-up care and reliable evidence on early prognostic factors. However, the existing literature is sparse and methodologically heterogeneous, limiting the clinical applicability of findings. We therefore conducted a systematic review and meta-analysis to identify early risk factors for poorer long-term mental health and HRQoL outcomes. A systematic search of seven electronic databases identified studies of adult patients with TBI, with outcomes assessed at least 6 months postdischarge. Two authors independently screened the studies, assessed the risk of bias, and extracted the data. We pooled effect estimates using a random-effects meta-analysis and calculated 95% prediction intervals. A narrative synthesis was applied when meta-analysis was not feasible. The review was registered with PROSPERO (CRD42024576912) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 8,104 articles screened, 64 studies met the inclusion criteria (n = 334,672). Most studies (58%) had a low risk of bias. Female sex, socioeconomic disadvantage, psychiatric history, assaultive-related injuries, and previous TBI were consistently associated with worse long-term outcomes. Across meta-analyses, assault-related injuries more than doubled the odds of post-traumatic stress disorder (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 2.01-3.66, I2 = 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, I2 = 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, I2 = 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, I2 = 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, I2 = 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, I2 = 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, I2 = 98%) were associated with higher odds of depression. Furthermore, higher pooled anxiety scores were observed in females and in individuals with a psychiatric history. The study identified several readily available factors present before or at discharge that are associated with poor long-term HRQoL and mental health outcomes. Leveraging these factors in follow-up protocols, prediction modeling, and clinical decision support systems may facilitate risk-stratified postdischarge care for TBI patients.

Humans

Hydrodissection-assisted laparoscopic orchiopexy utilizing needle grasper for palpable undescended testes: Clinical efficacy analysis.

OBJECTIVE: Laparoscopic orchiopexy has emerged as a viable alternative for the treatment of palpable undescended testis (UDT). This study aims to evaluate the feasibility and efficacy of needle-grasper hydrodissection-assisted laparoscopic orchiopexy (NHLO) in comparison to conventional laparoscopic orchiopexy (CLO) for palpable UDT. METHODS: A cohort of 96 patients diagnosed with palpable UDT, admitted between January 2020 and April 2024, was included in this study. Among these, 54 patients underwent NHLO, while 42 patients were treated with CLO. In the NHLO procedure, normal saline was injected into the retroperitoneal space to create a hydrodissection barrier, facilitating the separation and protection of the vas deferens and spermatic cord. The vas deferens and spermatic cord were meticulously dissected following the principles of integrity and minimal tissue trauma. Outcome measures included final testicular position, testicular volume growth, testicular atrophy, success rate, and postoperative complications. RESULTS: No significant differences were observed between the NHLO and CLO groups in terms of age, laterality, operative time (NHLO: 38-46 min; CLO: 39-48 min), or complication rates (NHLO: 1.9 %; CLO: 0.0 %). At follow-up, all patients in both groups exhibited palpable testes in satisfactory scrotal positions. Notably, no visible abdominal scarring was observed in the NHLO group, whereas there were two noticeable scars on the abdomen in CLO. CONCLUSION: Needle-grasper hydrodissection-assisted laparoscopic orchiopexy is a safe, effective, and minimally invasive technique that provides optimal protection of the vas deferens and spermatic cord while achieving excellent cosmetic outcomes.

Humans

Factors associated with additional intervention requirement following ESWL in pediatric patients with urolithiasis.

OBJECTIVE: To identify predictors of additional intervention following extracorporeal shock wave lithotripsy (ESWL) in pediatric patients and to develop a clinically applicable predictive model. MATERIALS AND METHODS: This retrospective cohort study included 647 pediatric patients who underwent ESWL between 2015 and 2025. Demographic, clinical, and radiological variables were analyzed. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of additional intervention. Model performance was evaluated using receiver operating characteristic curve analysis. RESULTS: Additional intervention was required in 65 patients (10.0%). On multivariable analysis, stone size 10-20 mm (OR: 3.04, p = 0.003), moderate (OR: 2.16, p = 0.049) and severe hydronephrosis (OR: 6.05, p < 0.001), and multiple stones (OR: 3.52, p = 0.030) were identified as independent risk factors. Increasing age (OR: 0.84, p = 0.026), history of urolithiasis (OR: 0.41, p = 0.006), and lower calyx location (OR: 0.14, p = 0.034) were associated with a reduced risk. The model demonstrated good discriminative performance (AUC: 0.794), with a sensitivity of 72% and specificity of 75%. Internal validation using bootstrap resampling demonstrated stable model performance, yielding a corrected AUC of 0.732. CONCLUSION: Stone burden, hydronephrosis severity, and stone multiplicity are key determinants of additional intervention after ESWL in pediatric patients. The proposed model shows good predictive performance and may support individualized risk stratification and clinical decision-making.

Humans

Gene expression patterns in the intestines of sea urchins (Strongylocentrotus intermedius) under prolonged high-salinity stress.

The effective development of high-salinity aquaculture for the sea urchin Strongylocentrotus intermedius depends on understanding its molecular mechanisms. Therefore, we conducted a 60-day experiment to investigate the effects of prolonged high-salinity stress on the survival, growth, amino acid levels, antioxidant enzyme activity, and gene expression of S. intermedius. The experiment involved the preparation of two groups: one with a salinity of 32 (group S32) and another with 36 (group S36). The results showed that the survival rate of S. intermedius in group S36 was 80%&#xa0;&#xb1;&#xa0;6.7%, while the weight gain rate was only 61.58%&#xa0;&#xb1;&#xa0;1.92%. Both parameters were significantly lower than those in group S32 (P&#xa0;<&#xa0;0.05). In addition, the GSH, Cys, and Glu expression in S. intermedius was significantly higher than that observed in group S32 (P&#xa0;<&#xa0;0.05). The transcriptomic results showed that, when comparing groups S32 and S36, 179 differentially expressed genes were identified. These genes were predominantly enriched in pathways related to metabolism and amino acid biosynthesis. We highlight the genes CGL, EAAT3, AMY, and NADH, which are associated with the energy metabolism, cysteine transport, and amino acid biosynthesis of S. intermedius. We speculated that S. intermedius exposed to high salinity enhances energy metabolism, as well as Cys synthesis and transport, to mitigate oxidative stress. This study provides a theoretical reference for the healthy aquaculture of S. intermedius in high-salinity environments.

Animals

Assessing the public health impact of routinely collected electronic healthcare record data in NICE guidelines: A systematic review of CPRD research.

OBJECTIVES: Evidence used in NICE guidance has traditionally prioritised randomised controlled trials, but increasing availability of electronic health record (EHR) data has expanded opportunities for real-world evidence. The Clinical Practice Research Datalink (CPRD) is a commonly used UK primary care EHR resource, yet the extent to which CPRD studies have informed NICE guidelines in the past decade is unclear. STUDY DESIGN: The systematic review was conducted in accordance with PRISMA guidelines. METHODS: We conducted a systematic review of CPRD studies in PubMed, MEDLINE, and Embase published between 04/16-09/25. For each eligible CPRD study, targeted searches of NICE guidelines were performed to identify explicit citations in NICE guidelines. Two reviewers screened and extracted data independently, resolving disagreements by consensus or third reviewer. Guideline information, number of guidelines over time, type of guidelines, and disease area guidelines (using British National Formulary (BNF) chapters) were described. RESULTS: 7181 records were identified. After de-duplication, 2704 unique CPRD studies were screened against NICE guidelines. Of these, 92 CPRD-based studies met inclusion criteria and were cited across 67 NICE documents. The annual number of NICE guidelines citing CPRD studies increased between 2016 and 2025; 1.5% of identified guidelines published in 2016 and 27.7% in 2025. The guideline citing the most CPRD studies was cancer related. The most common types of guidelines included clinical guidelines (49.3%) and technology appraisals (32.8%). Guidelines made up 12 different BNF categories, most frequently central nervous system related (23.9%; n&#x202f;=&#x202f;16). CONCLUSION: Observational CPRD studies are increasingly referenced in NICE guidelines across multiple disease areas, supporting the growing role of EHR data in national guideline development.

Clinical studies

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48&#xa0;h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5&#x2009;kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans

Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies.

The dopaminergic system has long been a central focus of functional neuroimaging. Positron emission tomography (PET) with the D2/D3 receptor radioligand [11C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [11C]raclopride PET studies (n&#x2009;=&#x2009;1640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p&#x2009;<&#x2009;0.001), and approximately twice that of alcohol (4.8%, p&#x2009;<&#x2009;0.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p&#x2009;>&#x2009;0.14) or overall striatum (p&#x2009;>&#x2009;0.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [&#xb9;&#xb9;C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.

Journal Article

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 &#xb1; 0.28) % and (17.67 &#xb1; 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 &#xb1; 0.21) % and (25 &#xb1; 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 &#xd7; 10&#x2079; vg/eye), medium (3 &#xd7; 10&#x2079; vg/eye), or high (1 &#xd7; 10&#xb9;&#x2070; vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (&#x2265;100 vs <90 &#xb5;V in controls at 10 cd&#xb7;s/m&#xb2;) and photopic b-wave amplitudes (49-66 vs 31-46 &#xb5;V at 30 cd&#xb7;s/m&#xb2;) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan&#xae; for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans

Nasopharyngeal Carriage Rate, Risk Factors, and Co-Resistance Patterns of Methicillin-Resistant Staphylococcus aureus in Ethiopia: Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) nasopharyngeal carriage is a major global health concern linked to severe infections and transmission. However, comprehensive evidence on the burden of MRSA carriage, antimicrobial resistance, and associated risk factors in Ethiopia remains limited. This study aimed to estimate pooled prevalence, resistance pattern, and determinants of nasopharyngeal MRSA carriage. PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and gray literature were searched for cross-sectional studies published between January 2015 and December 2025. Two groups of reviewers screened studies based on predefined criteria. The risk of bias was assessed using the Joanna Briggs Institute tool. Pooled prevalence and resistance proportions were estimated using a random-effects model, and pooled odds ratios (ORs) were calculated using the Mantel-Haenszel method. Heterogeneity and publication bias were assessed, and a sensitivity analysis was conducted. A total of 1040 records were identified, and 20 studies (6869 participants) were included. The pooled carriage prevalence was 7.3% (95% CI, 5.0-10.8), with substantial heterogeneity (I2&#x2009;=&#x2009;95.5%). Resistance was highest to tetracycline (55.75%) and lowest to clindamycin (12.66%). Increased odds of carriage were associated with prior hospitalization (OR, 3.49) and antibiotic use (OR, 2.35). Inconsistent variable coding across included studies limited the inclusion of other potential risk factors. Evidence of publication bias was detected, suggesting that the pooled prevalence should be interpreted with appropriate caution. The findings indicate a considerable burden of MRSA and highlight the need for strengthened antimicrobial stewardship, improved surveillance, and targeted prevention efforts in higher-risk populations. This review was registered in PROSPERO (CRD420251047192).

Ethiopia

Performance comparison of rapid and native barcoding methods for Oxford Nanopore sequencing of Poliovirus Viral Protein 1 (VP1) amplicons.

Accurate and timely sequencing of poliovirus is critical for global eradication efforts, particularly for molecular epidemiology based on the typing region of the genome, viral protein 1 (VP1). While Oxford Nanopore Technologies (ONT) sequencing has expanded capabilities for poliovirus surveillance, the relative performance of different ONT library preparation methods, including ligation-based (Native Barcoding) and transposase-based (Rapid Barcoding) approaches, has not been systematically evaluated. In this study, we compared rapid barcoding and native barcoding workflows for sequencing VP1 amplicons from 17 type 2 poliovirus-positive samples, each processed in triplicate. Native barcoding generated significantly more sequencing output, producing approximately 2.3-fold greater total read yield than rapid barcoding, and demonstrated higher run-to-run reproducibility (R2 = 0.979-0.998 vs. 0.847-0.929, respectively; p&#x202f;<&#x202f;0.001). In addition, native barcoding generated 80% of the total yield achieved by rapid barcoding within approximately 7&#x202f;h, whereas rapid barcoding required approximately 40&#x202f;h to reach the same output. Despite these differences, both methods produced identical VP1 consensus sequences across all samples, with comparable read quality (median per-base Q-scores of approximately Q17-Q18). Rapid barcoding provided substantial practical advantages, reducing hands-on library preparation time (55 vs. 200&#x202f;min) and per-sample cost ($12.82 vs. $16.54), while simplifying workflow and reducing technical complexity. These findings indicate that sequencing yield may not be a determinant of downstream analytical outcomes for poliovirus VP1 ONT sequencing. Rapid barcoding therefore represents a cost-effective and efficient approach for routine poliovirus surveillance, whereas native barcoding remains advantageous in applications requiring rapid data generation or maximal sequencing depth.

Poliovirus

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans

Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor: A&#xa0;Randomized Trial.

BACKGROUND: Individuals residing in the southeastern United States experience disproportionately worse stroke outcomes. Although blood pressure (BP) reduction is among the most effective strategies for improving stroke outcomes, fewer than one third of survivors of stroke achieve BP control within 1 year of the index event. METHODS: The PACESETTER (Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor) trial enrolled patients with stroke and uncontrolled BP from 3 safety-net health care systems in South Carolina. Patients were randomized 1:1 to the PACESETTER intervention, which included a Bluetooth-enabled electronic pill tray, a BP monitor, and a smartphone application for automated data transmission of medication adherence and BP data to a central server or to usual care. The primary outcome was systolic BP <130&#x2009;mm&#x2009;Hg at 12 months, analyzed according to the intention-to-treat principle. RESULTS: The trial was stopped early due to low recruitment during the COVID-19 and funding constraints. Between September 2019 and February 2023, 120 participants were randomized to PACESETTER (n=60) or the usual care arm (n=60). At 4&#xa0;months, systolic BP <130&#x2009;mm&#x2009;Hg favored the PACESETTER arm (48.8% versus 29.3%, P=0.07), but no significant difference was observed at 12 months (50% versus 47.2%, P=0.82). CONCLUSIONS: Because the trial was terminated prematurely, the effect of the PACESETTER intervention on 12-month BP control after stroke remains uncertain. A trial completed to its full term and sufficiently powered to also evaluate key short-term end points is needed. REGISTRATION: URL: https://www.clinicalstrial.org; Unique Identifier: NCT03401489.

Aged

Desert-derived Ensifer sp. SA403 enhances potato salt tolerance by reshaping rhizosphere microbiome functions and host responses.

Soil salinization increasingly threatens global food security, and potato (Solanum tuberosum L.), a moderately salt-sensitive crop, is particularly vulnerable to saline soils. Plant growth-promoting rhizobacteria (PGPR) offer a promising strategy to improve crop performance, yet how PGPR interact with native microorganisms to enhance potato salt tolerance remains poorly understood. In this study, we identified a desert-derived PGPR strain, Ensifer sp. SA403, which substantially enhanced potato performance under high salinity across sterile, non-sterile and field conditions. Physiologically, inoculation with SA403 reduced shoot Na&#x207a; accumulation and increased the K&#x207a;/Na&#x207a; ratio; notably, these effects were markedly stronger in non-sterile substrates than under sterile conditions, indicating that SA403-mediated ion homeostasis relies on cooperation with the resident microbiota rather than on the strain acting alone. Metagenomic profiling indicated that SA403 strain reshaped rhizosphere communities, significantly enriching beneficial taxa such as Priestia and Bradyrhizobium, and upregulated functional pathways involved in glutathione and sulfur metabolism. Furthermore, host transcriptomic analyses showed that SA403 modulated plant responses to salt stress, with differentially expressed genes enriched in jasmonic acid signaling, ethanolamine metabolism and amino-acid biosynthesis pathways. Field trials on saline soils confirmed that SA403 significantly increased seedling emergence and tuber weight. Together, our results demonstrate that SA403 functions as a biological mediator that optimizes rhizosphere microecology and coordinates ion balance and host signaling to enhance potato salt tolerance. These findings support the potential of SA403 as a robust PGPR-based tool for sustainable potato production on saline soils.

Rhizosphere