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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·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

Medically Unexplained Symptoms: A Systematic Umbrella Review of Current Terminology and Reported Rationales.

OBJECTIVES: Toaddress current naming conventions for Medically Unexplained Symptoms (MUS) through a systematic umbrella review. The terminology used and the provided rationales were considered. METHODS: Registered with PROSPERO (CRD42024526020), this review searched 8 key databases, last on January 28, 2025. Reviews including medically unexplained symptoms (or synonym or subtype) in their systematic search terms were included (N=422). RESULTS: A total of 577 references to 111 terms were made across the reviews, with numerous reviews using the same overarching terms, including "functional" (n=233), "somatic" (or variants thereof, n=51), and "medically unexplained" (n=28). Thirty percent of terms (n=179) were to specific syndromes or terms that did not group together under an overarching term, suggesting substantial variability in terms, even though over 60% of authors were primarily associated with just 3 disciplines: medicine, allied health, and psychology. A subset of 23 reviews provided rationales, which were subjected to content analysis and a ROBIS (Risk of Bias in Systematic Reviews) risk-of-bias assessment. This analysis showed that rationales tended to (1) highlight differences between psychological, psychiatric, and other medical fields (n=7); (2) focus on the patient perspective and patient-practitioner therapeutic relationship (n=10); or (3) follow broad and/or commonly used terms (n=7). DISCUSSION: The current landscape of terminology used for MUS remains varied, nuanced, and inconsistent between disciplines. Moving forward to a more universal language accepted and used by both patients and practitioners would aid in the diagnosis, management, and treatment of MUS.

Humans

Effects of strength and balance training on the structure of the aging brain.

BACKGROUND: While it is established that motor training induces structural changes in the brains of young adults, structural adaptations in aging brains are less studied. METHODS: This randomized controlled study investigated the impact of long-term strength and balance training on the structural plasticity in 60 elderly adults (64 - 82 years old, 70.6 ± 4.7) using multi-modal neuroimaging. We compared the effects of three months of strength training to balance training of the same duration and to a passive control group. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to assess grey matter (GM) and white matter (WM) plasticity. White matter tract integrity (WMTI) modelling was employed to explore the microstructural underpinnings of white matter alterations. RESULTS: We found that strength training was associated with changes in diffusion metrics consistent with white matter microstructural remodeling, specifically increased extra-axonal axial diffusivity in the bilateral inferior fronto-occipital and longitudinal fasciculi. Additionally, both balance and strength training mitigated reductions in axonal water fraction in the splenium of the corpus callosum and the right posterior corona radiata observed in the control group. CONCLUSION: These results underscore the potential relevance of strength and balance training to induce beneficial neural plasticity by counteracting aging-related demyelination in the corpus callosum and highlight the specific role of strength training in facilitating white matter reorganization in key transmission fiber pathways.

Humans

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n = 38) or to the control group (n = 37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n&#x200a;=&#x200a;70) or cefoxitin (n&#x200a;=&#x200a;70), 2&#x2005;g every 8&#x2005;h for 5&#x2005;days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P&#x200a;=&#x200a;0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P&#x200a;=&#x200a;0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P&#x200a;=&#x200a;0.753), and mortality was 15.7% and 12.9%, respectively (P&#x200a;=&#x200a;0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n&#x202f;=&#x202f;10), positive control (PC; 400IU commercial non-recombinant eCG; n&#x202f;=&#x202f;20), or treatment group (T; 400IU r-eCG; n&#x202f;=&#x202f;15). Ewes were inseminated with fresh-diluted semen (200&#x202f;&#xd7;&#x202f;106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P&#x202f;<&#x202f;0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P&#x202f;<&#x202f;0.05). On day 13, largest follicle diameter did not differ (P&#x202f;>&#x202f;0.05) among groups; however, fewer follicles > 2&#x202f;mm occurred in PC than NC and T (P&#x202f;<&#x202f;0.05). CL number was higher in T than PC (2.0&#x202f;&#xb1;&#x202f;0.3 vs. 1.0&#x202f;&#xb1;&#x202f;0.0, P&#x202f;<&#x202f;0.01), while NC did not differ (1.0&#x202f;&#xb1;&#x202f;0.25). Conversely, pregnancy rate was higher (P&#x202f;<&#x202f;0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P&#x202f;=&#x202f;0.92 and P&#x202f;=&#x202f;0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals

Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50&#xa0;&#x3bc;L) was deposited onto squares of black cotton and exposed to 45&#xa0;&#xb0;C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28&#xa0;days (n&#xa0;=&#xa0;5 per day, per climate condition). Source testing included AP test reagent, ABAcard&#xae; p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ&#x2122; System (Promega, Australia) and quantified using Quantfiler Trio&#x2122; (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p&#xa0;<&#xa0;0.01) and the number of sperm observed decreased significantly (p&#xa0;<&#xa0;0.01). All ABAcard&#xae; p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45&#xa0;&#xb0;C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5&#xa0;ng, IQR: 87.5&#xa0;ng) compared to day 0 (181.5&#xa0;ng, IQR: 1172.4&#xa0;ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

Humans

Not just when, but how: An exploratory dual-control approach to video feedback in motor learning.

The present study provides exploratory evidence for a novel dual-control paradigm. It examines whether combining temporal over video feedback timing with learner-controlled interactive playback functions (pause, slow-motion, rewind) would enhance motor skill acquisition beyond temporal autonomy alone. Sixty-four novice adults were randomly assigned to one of four conditions: Full Control (self-controlled timing + interactive replay), Partial Control (self-controlled timing + non-interactive replay), Yoked Full Control (externally controlled timing + interactive replay), or Yoked Partial Control (externally controlled timing + non-interactive replay). Motor accuracy (Radial Error), movement consistency (Bivariate Variable Error), technical execution, and self-efficacy were assessed at pre-test, 24-h retention, and 72-h retention following two acquisition sessions on a dart-throwing task (120 trials total). The Full Control group demonstrated the greatest and most durable learning gains across all outcomes. The Group &#xd7; Time interaction was significant across all dependent variables (&#x3b7;2&#x209a; ranging from 0.140 to 0.234), with Full Control demonstrating superior retention at both 24 and 72&#xa0;h relative to other groups (though differences relative to Partial Control were more pronounced at 72-h retention). Critically, the Yoked Full Control group showed comparatively weaker outcomes despite access to the same interactive playback functions. These findings suggest that interactive video tools may be most useful when learners can regulate both when feedback is accessed and how it is inspected. Theoretical and practical implications for the design of learner-centered video feedback systems are discussed.

Humans

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

Evaluation of the intraoperative analgesic effects of perioperative electroacupuncture: a randomised, blinded clinical trial in dogs.

OBJECTIVE: To evaluate the effect of perioperative electroacupuncture (EA) on intraoperative analgesic requirements in dogs undergoing tibial tuberosity advancement (TTA) surgery. STUDY DESIGN: Prospective, randomised, blinded, controlled clinical study. ANIMALS: A group of 29 client-owned dogs diagnosed with cranial cruciate ligament rupture that underwent TTA surgery. METHODS: Dogs were treated with EA at predefined acupuncture points (LI-4, ST-36, LIV-3, SP-6 and GB-34) perioperatively as additional analgesia (group EA, n = 14) or were allocated to the control group (group C, n = 15). All dogs were anaesthetised with a standardised protocol including methadone, dexmedetomidine, propofol and ketamine. The intraoperative delivery of sevoflurane and fentanyl was guided in response to signs of nociception by a purpose-designed flowchart, by the same anaesthetist who was blinded to treatment group. A Wilcoxon rank sum test was applied for the fentanyl consumption analysis. Heart rate, mean arterial blood pressure and end-tidal sevoflurane were descriptively analysed between groups for specific time points. A p value < 0.05 was considered significant. RESULTS: The EA group needed significantly less fentanyl with 0.7 (0-2.7) &#x3bc;g kg-1 hour-1 administered versus 2.0 (1.2-5.5) &#x3bc;g kg-1 hour-1 in group C (p = 0.031). Fifty percent of the EA group was not administered a fentanyl bolus, whereas all dogs in group C required at least one bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Perioperative EA reduced mean fentanyl consumption by more than 60% in dogs undergoing TTA surgery.

Animals

Glaucoma filtering surgery combined with phacoemulsification in the era of new aqueous humor filtration devices: A systematic review.

We evaluate the efficacy and safety of filtering glaucoma surgeries combined with phacoemulsification (PCE)-including new aqueous humor drainage devices-compared to standalone procedures. We performed a systematic search up to March 23, 2025, including all comparative studies assessing trabeculectomy (TRAB), non-penetrating deep sclerectomy (NPDS), Xen&#xae; Gel Stent (XEN), or Preserflo&#xae; MicroShunt (PMS) combined with PCE, versus the same surgery alone. Key exclusion criteria include inadequate follow-up (less than 12-month), absence of a defined success criterion, more than 50% of loss to follow-up at 12-month, and lens extraction performed without PCE. Main outcome was surgical success at &#x2265;&#x202f;12 months. Secondary outcomes included intraocular pressure (IOP) reduction, decrease in hypotensive medications, and rates of complications. A total of 27 studies were included for analysis. Among studies comparing TRAB/PCE with standalone TRAB, half reported similar success rates, while others favored standalone TRAB, particularly using strict IOP thresholds. Safety profiles were comparable. For NPDS/PCE, data mostly showed equivalent outcomes versus standalone NPDS, with comparable safety. In studies on XEN/PCE and PMS/PCE, results suggested similar rates of surgical success, efficacy in IOP and medication reduction, and safety compared to their stand-alone procedures. Small differences occasionally favored standalone procedures under stricter success definitions. Current evidence suggests that combined filtering glaucoma surgery provides long-term efficacy and safety comparable to standalone, though some subgroups and outcome thresholds may slightly favor standalone approaches. The limited availability of high-quality prospective trials underscores the need for further large-scale robust studies.

Humans

Smoke-Free Home Intervention in Permanent Supportive Housing: A Cluster Randomized Clinical Trial.

IMPORTANCE: Chronic diseases related to tobacco use and secondhand smoke exposure are the leading causes of death among formerly homeless adults living in permanent supportive housing (PSH) in the US. OBJECTIVE: To evaluate the efficacy of a brief, smoke-free home intervention in promoting voluntary smoke-free home adoption among PSH residents. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial, data collection occurred from January 11, 2022, to March 31, 2025. Participants were residents aged 18 years or older who smoked cigarettes at home in 40 multiunit PSH sites in the San Francisco Bay area, randomized to intervention or waiting list control clusters, and housing staff who worked at the study sites. INTERVENTION: Residents in intervention sites received one-on-one in-person coaching from research staff on adopting a smoke-free home; waiting list control site residents received no interventions during the study but were offered the intervention once the intervention group completed follow-up. Staff in both intervention and control sites received training on providing brief tobacco cessation coaching. MAIN OUTCOMES AND MEASURES: Primary outcomes were smoke-free home adoption for at least 90 days and 7-day carbon monoxide-verified point prevalence abstinence (PPA; expired carbon monoxide level &#x2264;5 ppm) at 6 months. Secondary outcomes were any adoption (&#x2265;1 day) of a smoke-free home in the past 90 days among residents and changes in Smoking Knowledge, Attitudes, and Practices (S-KAP) scores among staff. RESULTS: The trial enrolled 400 residents (mean [SD] age, 54.5 [10.7] years; 251 [63.1%] male), 191 in the intervention and 209 in the control cluster. At 6 months, 13 residents (6.8%) in the intervention and 10 (4.8%) in the control group adopted a smoke-free home for at least 90 days (odds ratio [OR], 1.45; 95% CI, 0.69-3.07). Few residents achieved 7-day PPA, though more intervention residents (12 [6.3%]) achieved it compared with controls (2 [1.0%]) (OR, 6.94; 95% CI, 1.69-28.45). Intervention residents had greater odds than control residents of any smoke-free home adoption of at least 1 day (121 [63.4%] vs 77 [36.8%]; adjusted OR, 3.83 [95% CI, 2.63-5.57]). Among staff, mean (SD) S-KAP scores increased at 6 months vs baseline for beliefs (by 0.21 [0.55] points) and practices (by 0.24 [0.61] points) pertaining to providing cessation treatment. CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, the brief intervention did not result in a significant increase in smoke-free home adoption for at least 90 days, though more residents in the intervention than the control group attempted adoption for at least 1 day. These findings support the scalability of this approach to reduce smoking in PSH, but more intensive interventions may be needed to sustain intervention effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04855357.

Humans

Joint association of sedentary behaviour and physical activity with cardiovascular disease: a systematic review and meta-analysis.

This systematic review and meta-analysis of cohort studies aimed to synthesize existing evidence on the joint association of physical activity (PA) and sedentary behaviour (SB) with cardiovascular disease (CVD) risk among adults. We searched PubMed, EMBASE, and Cochrane for English studies published between January 2010 and February 2025 that examined the joint association of PA and SB (fatal and non-fatal) CVD among adults and pooled their results through meta-analyses using study-level data. Using findings from 17 studies, the pooled effect size for the lowest PA + highest SB group was 1.78 (95% CI: 1.59-2.00), suggesting increased risk for CVD compared with the reference group (i.e. highest PA + lowest SB). Compared with the same reference group, we found an increased risk for CVD in the lowest PA + lowest SB (HR = 1.25, 95% CI: 1.12-1.40) and the highest PA + highest SB (HR = 1.16, 95% CI: 1.06-1.27) groups. Subgroup analyses according to domains or types of PA and SB exposure, outcome measures, and exposure measurement method revealed a similar pattern. In conclusion, individuals with the lowest PA combined with the highest SB may experience an increased risk for CVD events compared with those with the highest PA and lowest SB. There was also an increased risk for individuals with a combination of either low PA + low SB and high PA + high SB, albeit to a lesser extent. Although substantial study-level heterogeneity exists, the results highlight the potential value of considering both behaviours jointly in relation to CVD risk.

Humans

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans

Aquablation/AquaBeam Waterjet Therapy for Benign Prostatic Hyperplasia: Three-Year Functional and Ejaculatory Outcomes in a Multicenter Real-World Italian Cohort.

OBJECTIVE: To evaluate the 3-year functional outcomes of Aquablation/AquaBeam waterjet therapy for bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), with particular attention to urinary symptoms, quality of life, continence, ejaculatory function, and complications. METHODS: We performed a retrospective analysis of a prospectively maintained multicenter database including 218 consecutive men who underwent Aquablation/AquaBeam for symptomatic BPH between January 2019 and January 2022 at three referral centers. Functional outcomes assessed preoperatively and during follow-up included International Prostate Symptom Score (IPSS), IPSS quality-of-life item (IPSS-QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), continence, and ejaculatory function. Median follow-up was 36&#x2009;months. Ejaculatory preservation was evaluated only in patients with preserved antegrade ejaculation at baseline. RESULTS: Median age was 61&#x2009;years (IQR 57-66), median prostate-specific antigen (PSA) was 2.52&#x2009;ng/mL (IQR 0.40-21.60), and median prostate volume was 55&#x2009;mL (IQR 40-73). Median operative time was 56&#x2009;min, while median catheterization time and length of hospital stay were both 48&#x2009;h. Functional improvements were evident from the 3-month follow-up and remained stable through 36&#x2009;months. At 36&#x2009;months, median IPSS improved to 5 and median Qmax to 18&#x2009;mL/s. Median PSA changed modestly from 2.52&#x2009;ng/mL at baseline to 2.75&#x2009;ng/mL at 36&#x2009;months. No cases of de novo urinary incontinence were observed throughout follow-up. Among patients with preserved antegrade ejaculation at baseline, 87% maintained antegrade ejaculation at 36&#x2009;months. Most postoperative complications were minor (Clavien-Dindo grade I-II, 20.2%). One grade III rectal injury occurred (0.5%). Median hemoglobin decreased from 15.2&#x2009;g/dL preoperatively to 14.0&#x2009;g/dL before hospital discharge, and two patients required blood transfusion. During the 36-month follow-up, no surgical retreatment was required, whereas 11 patients (5.0%) received temporary medical retreatment. CONCLUSION: In this multicenter real-world cohort, Aquablation/AquaBeam was safe and effective over 3&#x2009;years, providing durable improvement in lower urinary tract symptoms and quality of life while preserving continence and antegrade ejaculation in most patients. These findings support Aquablation/AquaBeam as a valuable minimally invasive surgical option for selected men with BPH, particularly those who prioritize preservation of ejaculatory function. Longer-term and comparative studies are warranted. TRIAL REGISTRATION: 48281.

Humans