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Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.

Humans

Genome-wide identification and expression analysis of the CREB/ATF family and its potential role in melanogenesis in the Manila clam (Ruditapes philippinarum).

Ruditapes philippinarum is an economically important bivalve species in China, and shell color is a trait of ecological and commercial significance. Melanin is a key determinant of shell color, and members of the CREB/ATF family have been reported to participate in melanogenesis in other organisms. In this study, members of the CREB/ATF family were systematically identified at the whole-genome level based on genomic and transcriptomic datasets, followed by analyses of their phylogenetic relationships, gene structures, and expression patterns. A total of six CREB/ATF family members were identified and classified into five subfamilies. Expression profiling and RT-qPCR validation revealed that most CREB/ATF genes were highly expressed in the mantle and displayed clear differences among shell-color phenotypes. Except for RpATF4 and RpCREBZF, most members exhibited relatively high expression levels in dark-colored shell strains, particularly in black and zebra-striped clams. Moreover, most genes showed low expression during early embryonic and larval stages but increased expression at the single-siphon spat and juvenile stages. These results suggest that the CREB/ATF family may be involved in melanin-associated shell-color regulation in R. philippinarum, providing important candidate genes and a theoretical basis for further elucidating the molecular mechanisms of shell-color formation in mollusks.

Animals

Teach-Back in Clinical Communication: A Systematic Review and Meta-analysis.

BACKGROUND: Teach-back has been identified as a high-quality clinical communication strategy. Our aim was to synthesize current literature on teach-back effectiveness. METHODS: We searched MEDLINE, Embase, and CINAHL Complete databases to identify relevant studies published between 2018 and 2026. We also included pre-2018 studies identified in prior systematic reviews. Studies were eligible for inclusion if they involved adult patients and/or care partners, delivered teach-back in a single encounter, had a comparator group, and reported proximal/intermediate patient outcomes (as defined in our conceptual model). Two independent investigators screened each citation at the title/abstract and full-text levels and assessed risk of bias. Study characteristics and results were extracted. When meta-analysis was performed, we used standardized mean differences (SMD) to estimate summary effects. We assessed certainty of evidence (COE) using Grading of Recommendations Assessment, Development and Evaluation (GRADE) domains. RESULTS: Our systematic review included 18 randomized controlled trials (RCTs) involving 1985 participants. Across 9 RCTs assessing knowledge acquisition, conceptual inconsistencies precluded meta-analysis. Overall, there was no clear pattern of the effect of teach-back on knowledge (very low COE). In a meta-analysis of 5 RCTs assessing self-efficacy (416 participants), we found that teach-back interventions led to a large increase in self-efficacy relative to usual care (SMD&#x2009;=&#x2009;2.40; 95%CI 0.37-4.44) (very low COE). In a meta-analysis of 7 RCTs assessing adherence to health behaviors (571 participants), teach-back interventions led to a large increase in adherence (SMD&#x2009;=&#x2009;1.04; 95%CI 0.45-1.64) (low COE). Meta-analyses for both self-efficacy and adherence had large confidence intervals that ranged from small to large effect sizes and had substantial heterogeneity. DISCUSSION: In this systematic review and meta-analysis, we did not identify a clear benefit of teach-back on knowledge acquisition but did find evidence that teach-back improves self-efficacy and self-reported, short-term adherence to health behaviors.

clinical communication

Teacher- Versus Video-Delivered Classroom Activity Breaks and Student Physical Activity: The PAAC-3 Trial.

BACKGROUND: Classroom activity breaks may increase moderate-to-vigorous physical activity (MVPA); however, few studies have compared teacher and video-delivered approaches under real-world conditions. METHODS: In this cluster randomized trial, 11 elementary schools were assigned to teacher-delivered (PAAC-T; 5 schools, 192 students) or video-delivered (PAAC-V; 6 schools, 276 students) classroom activity breaks across one academic year. Teachers were trained to deliver two 10-min breaks daily. Intervention delivery was tracked via a web-based platform, and classroom MVPA was assessed using accelerometers at baseline and follow-up. RESULTS: Implementation fidelity was low and highly variable, but comparable between PAAC-T (42.3&#x2009;&#xb1;&#x2009;57.1 activity breaks/teacher/year) and PAAC-V (39.2&#x2009;&#xb1;&#x2009;33.9; p&#x2009;=&#x2009;0.96), with teachers delivering &#x223c;50% of the intended daily activity. Classroom MVPA increased significantly in both groups (PAAC-T: 9.8&#x2009;&#xb1;&#x2009;15.9; PAAC-V: 9.1&#x2009;&#xb1;&#x2009;15.3&#x2009;min/day; p&#x2009;<&#x2009;0.001), with no intervention arm-by-time interaction (p&#x2009;=&#x2009;0.43). IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Classroom physical activity breaks may increase student MVPA, but effectiveness in elementary schools appears to depend on implementation fidelity, administrative support, and equitable system-level infrastructure. CONCLUSIONS: Modest increases in classroom MVPA were observed across both delivery formats, although low and variable implementation fidelity limited conclusions regarding effectiveness and highlighted the need for stronger implementation supports. TRIAL REGISTRATION: NCT03493139.

Humans

Safety and efficacy of Meridian sinew tuina (MST) for post-surgical upper limb lymphedema: a systematic review and meta-analysis.

BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z&#x2009;=&#x2009;20.81; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (&#x2265; 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z&#x2009;=&#x2009;10.62; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N&#x2009;=&#x2009;924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD&#x2009;=&#x2009;-1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD&#x2009;=&#x2009;-2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.

Humans

Influence of soil types with different soil-forming process on the qualitative and quantitative detection of microplastics by near-infrared spectroscopy.

Microplastics (MPs) have become a pressing global environmental threat, with soils-acting as sinks for MPs from multiple sources-gaining increasing attention. Near-infrared (NIR) spectroscopy offers a promising tool for MPs detection due to its rapid, non-destructive, and field-applicable features. Although previous studies have focused on the effects of individual soil components on the NIR detection performance of MPs, there is still a lack of systematic research on how the complex background-formed by the coupling of multiple physicochemical properties in natural soils-affects detection performance. This study focuses on soil types with different soil-forming processes, selected five representative agricultural soils to systematically evaluate how the combinations of physicochemical properties they represented affect the performance of NIR-based qualitative and quantitative analysis of MPs in soils. The results demonstrated that soil type significantly affected both the spectral response and detection performance of MPs. Brown Pedocals and Brown Earth exhibited clearer characteristic absorption and stronger linear responses, achieving higher identification accuracy under low (<1.5 %) or zero MPs concentrations and the best quantitative performance (R2 &#x2265; 0.988, prediction set root mean square error (RMSEP) &#x2264; 0.110 %). In contrast, Phaeozem and Red Soil were more prone to misclassification at low concentrations, while Fluvo-aquic Soil showed the poorest quantitative performance. This study is the first to reveal, at a holistic level, the critical constraints posed by natural soil complexity on the NIR detection of MPs, offering targeted empirical evidence to support the application of NIR technology in real-world soil environments.

Soil

Role of External Vibratory Lithoclast (Lithecbole) in Improving Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy (ESWL).

<b>Background and Objective:</b> Extracorporeal shock wave lithotripsy (ESWL) is a widely used non-invasive treatment for renal stones. However, its effectiveness in clearing stones located in the lower pole of the kidney is often limited due to the anatomical challenges that impede the spontaneous passage of fragmented stones. This study evaluate the efficacy and safety of External Physical Vibration Lithecbole (EPVL) when used as an adjunctive therapy following ESWL in patients with lower pole renal stones, with a focus on improving stone clearance rates. <b>Materials and Methods:</b> This prospective interventional study was conducted at Al Yarmouk Teaching Hospital over two years and included 100 patients with 10-15 mm lower pole renal stones. Patients were randomized into two groups: The ESWL alone and ESWL plus EPVL. All patients received two ESWL sessions (3000 shocks/session). The treatment group additionally received EPVL therapy using a flank-applied vibration device. Follow-up was performed using ultrasound and KUB radiography. Statistical analysis was conducted using appropriate tests with significance set at p<0.05. <b>Results:</b> Baseline characteristics, including age, gender, weight, stone size and location, were statistically comparable between groups. The mean stone size was 12.4&#xb1;1.7 mm. A significantly higher stone-free rate was observed in the ESWL+EPVL group compared to the ESWL-only group (66% vs. 48%, p = 0.027). Although the residual stone size showed a numerical difference favoring EPVL, it was not statistically significant (p = 0.11). Complication rates were low, mild and similar in both groups (p = 0.3). Logistic regression analysis revealed that smaller stone size (p<0.001) and lower patient weight (p = 0.030) were significantly associated with successful stone clearance. Subgroup analysis further confirmed that patients with stones <11 mm or a weight <70 kg had the highest stone-free rates. <b>Conclusion:</b> In this initial evaluation, EPVL demonstrated a safe and effective adjunct to ESWL in enhancing stone clearance for lower-pole renal stones. Its application was associated with improved treatment outcomes without increasing complication rates. Further studies with extended EPVL sessions and longer follow-up are warranted.

Humans

Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16&#x2009;G) or 18-gauge (18&#x2009;G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16&#x2009;G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18&#x2009;G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16&#x2009;G and 17.5 with 18&#x2009;G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist.

Humans

Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis.

BACKGROUND: In SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17&#x2009;604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor agonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups. METHODS: In this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104, 208 weeks) using multiple approaches, including Cox modeling. RESULTS: Baseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACE. The risk of MACE increased across baseline hsCRP level <2, 2-<10, and &#x2265;10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACE across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACE. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT. CONCLUSIONS: In SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03574597.

Humans

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase

RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD+/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

AKT/mTOR signaling pathway

Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial.

BACKGROUND: Orforglipron, an oral GLP-1 receptor agonist, requires further evaluation in east Asian populations with type 2 diabetes, given this group's distinct pathophysiological characteristics. This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes. METHODS: This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan. Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg). Randomisation was stratified by background therapy, baseline HbA1c (&#x2264;8&#xb7;5% or >8&#xb7;5%), and metformin use (yes vs no; applied only to &#x3b1;-glucosidase inhibitors, thiazolidinedione, and glinides). Investigators, participants, and site staff were not masked to treatment. The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron. This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J). FINDINGS: Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80&#xb7;7-87&#xb7;8) had at least one treatment-emergent adverse event (TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81&#xb7;5-92&#xb7;5]) than in the 3-mg (107 [81%, 73&#xb7;5-86&#xb7;8]) and 12-mg (114 [84%, 77&#xb7;4-89&#xb7;6]) groups. Most TEAEs were of mild (267 [67%, 61&#xb7;8-71&#xb7;0]) or moderate (63 [16%, 12&#xb7;5-19&#xb7;6]) severity. Discontinuations due to an adverse event occurred in 19 of 134 participants (14%, 95% CI 9&#xb7;3-21&#xb7;1) in the 36-mg group compared with seven of 132 (5%, 2&#xb7;6-10&#xb7;5) in the 3-mg group and 11 of 135 (8%, 4&#xb7;6-14&#xb7;0) in the 12-mg group. Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3&#xb7;8%, 1&#xb7;6-8&#xb7;6]; 12 mg: 8 [5&#xb7;9%, 3&#xb7;0-11&#xb7;3]; and 36 mg: 11 [8&#xb7;2%, 4&#xb7;7-14&#xb7;1]). Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0&#xb7;8-6&#xb7;3) and in three of 134 in the 36-mg group (2%, 0&#xb7;8-6&#xb7;4) groups. No level 3 (severe) hypoglycaemia events occurred. Outcomes were generally similar across background therapies. INTERPRETATION: Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes. FUNDING: Eli Lilly. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Aged

Efficacy and Safety of Anti-Obesity Medications for Weight Loss Maintenance in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIMS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of anti-obesity medications (AOMs) for long-term weight maintenance following initial weight loss in adults with overweight or obesity. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 October 2025. Eligible studies were randomised controlled trials (RCTs) comparing AOMs with placebo during the weight-maintenance phase in adults with overweight or obesity after initial weight loss achieved through lifestyle, dietary, surgical or pharmacological interventions. Outcomes included anthropometric indices, cardiometabolic measures, safety endpoints, quality of life and neuropsychiatric adverse events. Weighted mean differences (WMDs) and odds ratios (ORs), each with 95% confidence intervals (CIs), were pooled for continuous and categorical outcomes, respectively, using fixed-effect or random-effects models as appropriate. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. The protocol was registered with PROSPERO (CRD420261293040). RESULTS: A total of 12 RCTs comprising 4915 participants met the inclusion criteria. Compared with placebo, AOM therapy during the weight-maintenance phase was associated with prevention of weight regain and additional improvements in anthropometric and cardiometabolic outcomes. AOMs led to further reductions in body weight (BW, WMD: -8.68&#x2009;kg, 95% CI: -13.25 to -4.11), waist circumference (WC, WMD: -7.16&#x2009;cm, 95% CI: -10.34 to -3.98) and body mass index (BMI, WMD: -3.58&#x2009;kg/m2, 95% CI: -5.69 to -1.46). Additional benefits were observed for triglycerides, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Neuropsychiatric adverse events were generally comparable between groups, and available quality-of-life measures favoured AOM treatment. CONCLUSIONS: AOM therapy during the weight-maintenance phase can help prevent weight regain, provide further reductions in body weight and improve cardiometabolic risk factors in adults with overweight or obesity. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Further long-term trials are needed to clarify optimal treatment strategies and safety.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n&#x2009;=&#x2009;6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR&#x2009;=&#x2009;1.35, 95% CI 1.04-1.75, I2&#x2009;=&#x2009;0%) and active disease (RR&#x2009;=&#x2009;1.55, 95% CI 1.01-2.40, I2&#x2009;=&#x2009;50%). UST was associated with a higher risk of active disease (RR&#x2009;=&#x2009;1.30, 95% CI 1.06-1.60, I2&#x2009;=&#x2009;0%) and congenital anomalies (RR&#x2009;=&#x2009;2.08, 95% CI 1.30-3.32, I2&#x2009;=&#x2009;0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR&#x2009;=&#x2009;2.60, 95% CI 1.03-6.57, I2&#x2009;=&#x2009;0%) and low birth weight (RR&#x2009;=&#x2009;2.38, 95% CI 1.01-5.60, I2&#x2009;=&#x2009;0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

Barriers to physical activity in patients with systemic lupus erythematosus in the UK.

INTRODUCTION: Physical activity (PA) may play an important role as a non-pharmacological addition to the management of SLE for disease control and reduction of cardiovascular risk factors. Those with SLE have been reported to engage in PA less than the general population. OBJECTIVE: To describe PA patterns and patient-reported barriers to PA for people with SLE in the UK. METHODS: An online survey was conducted of adults aged&#x2009;&#x2265;&#x2009;18 years. Participants were recruited from posters in outpatient clinics, newsletters and Lupus UK social media platforms. Survey questions included demographic information, perception of disease activity, the International Physical Activity Questionnaire (IPAQ) and specific leisure time questions. RESULTS: Two hundred sixty-eight patients participated, with a median (IQR) age of 51 (39-59) years and SLE disease duration of 10 (4-20) years&#xa0;were included. SLE-diagnosis was collected by self-report. In those with complete IPAQ data, 178/228 (79.1%) were in a moderate/high activity group. Participants in this group were more likely to be in employment and had lower levels of fatigue and pain. Fatigue was the most reported barrier to PA, irrespective of activity levels. Participants in the low PA group were more likely to have SLE-specific barriers such as higher disease activity and higher pain scores. CONCLUSIONS: Perceptions and preferences in relation to PA differ greatly between individuals with SLE. The most common self-reported barrier to PA was fatigue. Exploration of individual perceptions of PA should form part of consultations, to address perceived barriers. Key Points &#x2022; Some patients with self-reported SLE can meet WHO physical activity targets, especially those who remain in work. &#x2022; Fatigue is the most frequently reported barrier to physical activity for patients, irrespective of their activity levels. &#x2022; People are less likely to engage in PA if they believe it will negatively affect their SLE.

Humans

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH&#x2082;O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO&#x2082;/FiO&#x2082;), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6&#x2009;>&#x2009;12.5), the PaO&#x2082;/FiO&#x2082; ratio and Cstat increased significantly after RM (PaO&#x2082;/FiO&#x2082;: 100.8&#x2009;&#xb1;&#x2009;30.3 vs. 125.4&#x2009;&#xb1;&#x2009;38.3&#xa0;mmHg, p&#x2009;<&#x2009;0.05; Cstat: 21.5&#x2009;&#xb1;&#x2009;5.8 vs. 28.0&#x2009;&#xb1;&#x2009;7.0&#xa0;mL/cmH&#x2082;O, p&#x2009;<&#x2009;0.001), Pdriv decreased (19.1&#x2009;&#xb1;&#x2009;3.5 vs. 15.6&#x2009;&#xb1;&#x2009;3.2 cmH&#x2082;O, p&#x2009;<&#x2009;0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6&#x2009;&#x2264;&#x2009;12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

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&#x2009;=&#x2009;38) or to the control group (n&#x2009;=&#x2009;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&#x2009;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

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans