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A hybrid effectiveness-implementation trial to integrate precision skin cancer risk feedback in federally qualified health centers.

BACKGROUND: Skin cancers are the most common type of cancer in the United States, occur in all segments of the population, and are preventable. Our previous research with primary care patients' demonstrated interest in and efficacy of a precision prevention intervention providing feedback on MC1R risk level (higher versus average) in combination with prevention education materials relative to a standard educational intervention. Our current study is a hybrid type 1 effectiveness-implementation trial deployed at six federally-qualified health centers. This paper presents the study protocol. METHODS: A community advisory panel will guide development of study materials and measures. Staff training at each clinic will be completed in-person. Patients will be approached and screened in-person. Those completing genetic testing and the baseline survey will be randomized to the precision versus standard intervention for each risk level with a target sample size of 286 for each combination. Primary outcomes of effectiveness, assessed at 6 and 12 months, include a tanning score (5 items assessing intentional and unintentional tanning), number of sunburns, conduct of a skin self-examination, and electronic health record documentation of clinician-patient communication about skin cancer prevention. Effectiveness comparisons will focus on the precision relative to the standard intervention among higher risk participants. Implementation data will be collected to identify barriers and facilitators. RESULTS: Effectiveness and implementation outcomes will be evaluated following study completion. CONCLUSIONS: Results will guide subsequent scale-up of the precision intervention, including modifications of the intervention as well as methods for implementation. CLINICAL TRIALS IDENTIFIER: NCT07222995.

Humans

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Driving Under the Influence of Cannabis Among U.S. Young Adults Who Use Cannabis: Evidence From the 2021-2024 National Survey on Drug Use and Health.

PURPOSE: To estimate the prevalence of driving under the influence of cannabis (DUIC) and identify associated factors among U.S. young adult drivers reporting past-year cannabis use. METHODS: This cross-sectional study analyzed pooled 2021-2024 National Survey on Drug Use and Health. The analytic data were restricted to drivers aged 18-25 years who reported past-year cannabis use (N = unweighted 17,141; weighted N = 10,814,381). The outcome was self-reported past-year DUIC. Independent variables included demographics, substance use, mental health, cannabis-related perceptions, and driving behaviors. These relationships were assessed by modified Poisson regression. RESULTS: The weighted prevalence of DUIC was 28.0%, representing approximately over three million young adults. DUIC prevalence increased with cannabis use frequency, from 2.51 times higher among those using cannabis 12-49 days (adjusted prevalence ratio [APR]: 2.51; 95% confidence interval [CI]: 2.29-2.75) to 3.63 times higher among those reporting use on 300-365 days (APR: 3.63; 95% CI: 3.60-3.76), compared with those using cannabis 1-11 days. Cannabis use disorder (APR: 2.34; 95% CI: 2.06-2.65), simultaneous alcohol and cannabis use (APR: 1.29; 95% CI: 1.28-1.30), and perceived easy cannabis availability (APR: 2.36; 95% CI: 2.33-2.39) were also associated with higher prevalence of DUIC. Nonenrollment in school and living in a state with a medical cannabis law were associated with lower DUIC prevalence. DISCUSSION: DUIC is highly prevalent among U.S. young adults who use cannabis, with a clear graded association across categories of cannabis use frequency. Public health interventions should address frequent use, cannabis use disorder, alcohol-cannabis co-use, and perceived cannabis availability.

Humans

Effect of Music on Pain, Anxiety, and Satisfaction During Intrauterine Device Application: A Randomized Clinical Trial.

This randomized controlled trial aimed to determine the effect of music played during intrauterine device (IUD) insertion on perceived pain, state anxiety, and satisfaction levels. The study was conducted with 70 women who applied to a maternal and child health and family planning center and were randomly assigned to the intervention and control groups using simple randomization. Data were collected using a Demographic Information Form, the State-Trait Anxiety Inventory (STAI-I), and the Visual Analog Scale (VAS), as well as Bluetooth speakers and the musical piece Evgeny Grinko-Valse. Participants in the intervention group listened to music before and during the IUD insertion procedure, whereas the control group received routine care only. Data were analyzed using SPSS version 26 with appropriate descriptive and inferential statistical methods. Women in the music group had significantly lower perceived pain (p&#x2009;<&#x2009;0.001) and state anxiety levels during the procedure (p&#x2009;=&#x2009;0.022), and significantly higher satisfaction levels compared with the control group (p&#x2009;<&#x2009;0.001). In addition, post-procedure state anxiety levels were positively correlated with pain intensity experienced during and after the procedure (r&#x2009;=&#x2009;0.542 and r&#x2009;=&#x2009;0.496, respectively; p&#x2009;<&#x2009;0.001), and negatively correlated with procedural satisfaction (r&#x2009;=&#x2009;-0.652; p&#x2009;<&#x2009;0.001). These findings suggest that listening to music during IUD insertion may help reduce pain and anxiety while potentially enhancing patient satisfaction. Trial Registration: NCT06215183.

Humans

Workforce Representation in Ophthalmology Oral Board Examiners and Examinees.

PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study. SUBJECTS: ABO oral board examiners and examinees. METHODS: We utilized data from the American Board of Ophthalmology (ABO) and Association of American Medical Colleges (AAMC) to assess board examiner and examinee demographic characteristics from 2011 to 2024. Examiner characteristics included gender, years of experience, initial certification year and average examiner score. Examinee characteristics included gender, years since residency graduation and exam outcome (pass/fail). We utilized logistic regression to examine temporal trends in examiner and examinee gender from 2013 to 2024. MAIN OUTCOME MEASURES: Gender distribution of examiners and examinees. RESULTS: Overall, the proportion of women examiners increased over the study period. Notably, the most pronounced increase occurred following the transition from in-person to virtual oral board exam administration in 2020, rising from 31.3% (95% CI: 24.1%-38.4%) in 2019 to 49.1% (95% CI: 43.8%-54.4%) in 2024 (p < .001). The percentage of women examinees remained stable (41.7% [95% CI: 37.6%-45.8%] in 2019; 37.5% [95% CI: 33.0%-42.0%] in 2024, p-value: .019). CONCLUSIONS: The representation of women among the ABO oral board examiners has increased significantly following the transition to virtual exams while the proportion of examinees remained stable. Strategies to increase flexibility in scheduling exams may be beneficial in continuing to improve examiner representation.

Humans

High-frequency contralesional dorsal premotor cortex and low-frequency contralesional primary motor cortex rTMS in subacute stroke with severe upper limb impairment: comparable motor outcomes and differential regional degree centrality changes.

BACKGROUND: The contralesional dorsal premotor cortex has been proposed as a potential neuromodulatory target for patients with severe upper limb impairment due to subacute ischemic stroke. This proof-of-concept study aimed to compare behavioral outcomes and resting-state neuroimaging findings between high-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex and guideline-supported low-frequency stimulation over the contralesional primary motor cortex. METHODS: In this randomized trial, 46 patients with severe upper limb impairment in the subacute stage after ischemic stroke were randomly assigned to receive either high-frequency rTMS over the contralesional dorsal premotor cortex or low-frequency rTMS over the contralesional primary motor cortex. Low-frequency stimulation over the contralesional primary motor cortex served as an evidence-supported active comparator for poststroke upper limb motor recovery. Stimulation was administered five times per week for two weeks using magnetic resonance imaging-guided neuronavigation. All participants received concurrent standard rehabilitation therapy. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes included the Arm Subscore of the Motricity Index, the Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index, and resting-state functional magnetic resonance imaging-derived degree centrality. RESULTS: Both groups showed significant improvements in the primary and secondary behavioral measures (p&#x202f;<&#x202f;0.01), with no significant between-group differences in the magnitude of change (p&#x202f;>&#x202f;0.05). In neuroimaging analyses, patients receiving high-frequency rTMS over the contralesional dorsal premotor cortex showed significantly greater degree centrality changes in the ipsilesional middle occipital gyrus, contralesional medial superior frontal gyrus, and contralesional middle frontal gyrus than those receiving low-frequency rTMS over the contralesional primary motor cortex (p&#x202f;<&#x202f;0.05). Within the high-frequency stimulation group, degree centrality changes in the ipsilesional middle occipital gyrus were positively correlated with improvements in the Fugl-Meyer Assessment for Upper Extremity (r&#x202f;=&#x202f;0.619, false discovery rate-corrected p&#x202f;=&#x202f;0.018). CONCLUSIONS: High-frequency rTMS over the contralesional dorsal premotor cortex produced behavioral improvements comparable to guideline-supported low-frequency rTMS over the contralesional primary motor cortex, without establishing superiority or formal non-inferiority. Exploratory neuroimaging analyses showed greater degree centrality changes in the ipsilesional middle occipital gyrus after high-frequency premotor stimulation, and these changes correlated with upper-limb motor improvement. These findings support further investigation of contralesional dorsal premotor cortex-targeted high-frequency rTMS for severe subacute post-stroke upper limb impairment. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2000038049.

Humans

"Abrazos, no Balazos": Intensity of Risk for Exposure to Violence and Armed Conflict Trajectories for Adolescents and Young Adults in M&#xe9;xico 2018-2024.

PURPOSE: "Abrazos, no balazos" (Hugs, not gunshots) is the approach to violence used by the Federal Mexican government from 2018 to 2024. This study identifies distinct conceptually useful latent class growth trajectories in the annual intensity of risk for exposure to events and fatalities from violence against civilians and battles for adolescents and young adults (AYAs) in M&#xe9;xico from 2018 to 2024. METHODS: Data are from the Armed Conflict Location and Event Data project. Latent class growth analyses were conducted with four longitudinal dependent variables assessed in seven sequential years (2018-2024). RESULTS: In most of the Mexican states, AYAs experienced low intensity-flat trajectories (p >.096) in the annual intensity of risk for exposure to events and fatalities from violence against civilians and battles. AYAs who lived in states with extremely, markedly, or moderately elevated 2018 intensities of risk for exposure to violence experienced decreasing trajectories (p =.000). One latent class with a mildly elevated-increasing trajectory (p =.000) in the annual intensity of risk for exposure to violence was identified for each of the four longitudinal dependent variables. DISCUSSION: During the time that the Federal Mexican government used the "Abrazos, no balazos" approach, AYAs in the majority of the states in M&#xe9;xico had intensity of risk for exposure to violence and armed conflict trajectories that were consistent with the goals of primary and secondary violence prevention. Violence prevention efforts should be augmented in states with unfavorable trajectories.

Humans

Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans

Psychiatric Diagnoses and Psychotropic Medications Among Military-Affiliated Adolescents and Young Adults With Polycystic Ovary Syndrome.

PURPOSE: To study rates of psychiatric diagnoses and psychotropic medication prescription among U.S. military-affiliated adolescents and young adults (AYA) with polycystic ovary syndrome (PCOS). METHODS: This retrospective matched cohort study included U.S. military-affiliated AYA (aged 15-21 years) enrolled in TRICARE Prime for at least 6 months during the surveillance period (January 2016 to October 2023). Military-affiliated AYA were grouped into three categories: individuals diagnosed with PCOS (N = 6,911), age-matched individuals with no diagnosed PCOS symptoms (N = 35,814), and individuals with diagnosed symptoms suggestive of PCOS (N = 2,136). The presence of a psychiatric diagnoses and prescriptions for psychotropic medications were obtained via the International Classification of Diseases, 10th Revision, Clinical Modification codes and National Drug codes, respectively. RESULTS: AYA with diagnosed PCOS had higher odds of having a psychiatric diagnosis and being prescribed a psychotropic medication compared to an age-matched comparison group (psychiatric diagnosis odds ratio [OR] = 2.48 [2.35-2.62], medication OR = 2.14 [2.03-2.25]) and individuals with symptoms suggestive of PCOS (psychiatric diagnosis OR = 1.11 [1.003-1.23], medication OR = 1.16 [1.05-1.28]). DISCUSSION: The odds of psychiatric comorbidities and psychotropic medication prescription were more than twice as high as among U.S. military-affiliated AYA with PCOS. More research is needed to determine whether health-care utilization and military-related factors impact mental health outcomes among AYA with PCOS. Additionally, tailored, multidisciplinary mental health services for AYA with PCOS are needed.

Humans

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (&#x2265;15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41&#xa0;&#xb1;&#xa0;0.24 vs. 2.35&#xa0;&#xb1;&#xa0;0.06, P&#xa0;<&#xa0;0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An&#xa0;RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG&#xa0;(MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6&#x2009;months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3&#x2009;months (relative risk ratio [RRR]&#x2009;=&#x2009;0.717; 95% CI: 0.320-1.606) and 6&#x2009;months (RRR&#x2009;=&#x2009;0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6&#x2009;months (RRR: 0.698, 95% CI: 0.528, 0.929, p&#x2009;=&#x2009;0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6&#x2009;months and those who completed more MBS skills-building activities had less burnout at 3 and 6&#x2009;months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

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

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (&#x3b2; = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans

Safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in USA and Puerto Rico: Results from a Phase III, randomized, active-controlled study.

MenACYW-TT, a quadrivalent meningococcal tetanus toxoid-conjugate vaccine, is approved for prevention of invasive meningococcal disease in infants&#x2009;&#x2265;&#x2009;6&#x2009;weeks of age in the USA. This Phase III study (NCT03673462; September 17, 2018 - March 16, 2023) evaluated the safety of MenACYW-TT compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM197-conjugate vaccine (MenACWY-CRM) when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in a four-dose series (3+1 schedule). Participants were randomized 3:1 to receive MenACYW-TT (Group 1; n&#x2009;=&#x2009;2080) or MenACWY-CRM (Group 2; n&#x2009;=&#x2009;697) at 2, 4, 6, and 12&#x2009;months of age, with concomitant administration of routine pediatric vaccines (DTaP5-IPV/Hib, PCV13, rotavirus, hepatitis B, MMR, and varicella vaccines). Safety assessments included immediate unsolicited adverse events within 30&#x2009;minutes post-vaccination, solicited injection site and systemic reactions within 7d, unsolicited AEs within 30d, serious adverse events (SAEs) including adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) throughout the study. MenACYW-TT and MenACWY-CRM were overall well tolerated, and safety profiles were comparable. Solicited injection site reactions occurred in 84.9% and 84.6% of participants in Groups 1 and 2, respectively; solicited systemic reactions in 87.1% and 88.2%, respectively. During the entire study, 5.2% in Group 1 and 3.0% in Group 2 experienced at least one SAE; 0.9% and 0.1%, respectively, reported at least one AESI. Three deaths occurred in Group 1. All SAEs, AESIs, and deaths were unrelated to study vaccines. This study supports the safety profile of MenACYW-TT in infants and toddlers aged&#x2009;&#x2265;&#x2009;6&#x2009;weeks.Study registration: Clinicaltrials.gov: NCT03673462; EudraCT: 2019-004459-35.

Child, Preschool

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU&#xb7;mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays