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PubMed2026

Optimizing smoking cessation pharmacotherapy and counseling for adult primary care patients: a factorial randomized controlled trial.

BACKGROUND: Even with the most effective smoking cessation pharmacotherapies (i.e., varenicline or combination nicotine replacement [C-NRT]), the majority of people ultimately return to smoking. This research explored how to optimize the use of varenicline and C-NRT to promote smoking cessation. METHODS: Primary care patients participated in a 2x2x2x2 factorial experiment that evaluated 4 factors: 1) Medication Type (Varenicline vs. C-NRT [patch + mini-lozenge]), 2) Preparation (pre-quit) Medication (4 Weeks vs. Standard); 3) Medication Duration (Extended [24 weeks] vs. Standard [12 weeks]); and 4) Counseling Type (Cessation Counseling [4 sessions] vs. Referral Support [2 sessions focused on use of referral resources]). This study was discontinued prior to reaching the proposed sample size (N = 608) due to pandemic-related budgetary constraints. RESULTS: Participants (N = 496) were 55% women and 45.6% Black individuals. There were no statistically significant main effects of the 4 factors on abstinence at 12, 26 or 52 weeks. There was a 3-way interaction between Medication Type, Preparation Medication, and Counseling Type (p = 0.04) predicting the primary outcome of biochemically confirmed abstinence at 52 weeks; cessation counseling vs. referral support improved varenicline quit rates when 4 weeks versus 1 week of pre-quit medication was offered. For C-NRT, counseling type did not significantly improve quit rates regardless of the use of preparation medication. CONCLUSIONS: There was no robust evidence that enhanced pre-quit or extended duration of varenicline or C-NRT increased abstinence rates. More intensive counseling may support cessation for different pharmacotherapy regimens. Given the lack of consistent findings, this research should be viewed as exploratory to guide future research.

Humans↗

PubMed2026

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P = .03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P = .005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P = .15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P = .54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans↗

PubMed2026

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n = 2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120 Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5 mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans↗

PubMed2026

Optimizing eco-engineering pedogenesis of bauxite residues: Synergistic effects of humus and FeSO4/sulfur on microbial community and function.

Eco-engineered pedogenesis represents a promising approach for soil amelioration of bauxite residues (BRs) through exogenous organic matter. However, the role of humus in mediating this process remains poorly understood, significantly impeding the eco-engineering rehabilitation of BRs. In this study, we conducted pot experiments and subsequent microbial analysis to evaluate the individual improvement of humic acid (HA), fulvic acid (FA), and corn straw (SWZ) on the BRs' pedogenesis. High-throughput sequencing analysis revealed that both FA and SWZ were more effective than HA in steering microbial community assembly, as community diversity, dominant taxa enrichment, and species' interaction were all significantly higher (p < 0.05) in the FA/SWZ treatments than in HA treatments. Notably, the combination of FA with FeSO4 specifically enriched halophilic taxa, while FA coupled with sulfur (S) significantly improved the connectivity and complexity of the microbial network, as the average connection degree increasing from 1.008 to 1.113. Hydrolytic enzyme activity assays further indicated that FA, especially when combined with S, was the most effective treatment in restoring microbial function during BR pedogenesis. These findings highlight FA as a critical driver of microbial restructuring and functional recovery in BRs. Moreover, its efficacy can be enhanced by co-amendment with FeSO4 or S. This study provides important theoretical and practical insights for optimizing organic-inorganic amendment strategies to accelerate the eco-engineering pedogenesis of bauxite residues.

Humic Substances↗

PubMed2026

Applications of metal-organic frameworks in smart packaging for food freshness indication: a comprehensive review.

Smart packaging is extensively studied for its multifunctional capabilities in antimicrobial activity, preservation, and atmosphere modification. Recently emerged metal-organic frameworks (MOFs) freshness-indicating packaging becomes a key research direction in smart packaging owing to its distinctive functions and physicochemical properties. As multifunctional materials, the unique porous structure and tunable properties of MOFs provide a distinctive approach for developing food packaging applications dedicated to food freshness indication. Existing MOFs-based smart packaging still faces potential safety risks and technical challenges in practical applications, and there remains a lack of integrated discussion that combines synthesis strategies, packaging design, optimization, and safety assessment. This review elaborates on the application of MOFs in freshness-indicating smart packaging, focusing on diverse MOFs synthesis strategies, the formats of smart packaging, types of indicator signals, and qualitative/quantitative analytical methods. It also delves into the methodology concepts of MOFs-based smart packaging and evaluates MOFs safety in food packaging by addressing potential risks. Studies show that MOFs-based smart packaging achieves qualitative and semi-quantitative analysis of food freshness through multiple signal modalities such as visible color change, fluorescence, and photothermal effects. This review emphasizes that safe MOFs design is critically important and should comply with the overall migration limit of <10 mg/dm2 specified in Regulation (EC) No 1935/2004, lanthanide element limit of <0.05 mg/kg, and FDA threshold of 1.5 μg/person/day. Comprehensive safety assessment and intelligent sensing platforms will constitute pivotal directions for advancing MOFs-based smart packaging toward practical application.

Food Packaging↗

PubMed2026

Optimizing Initial Dosing for Tacrolimus and Mycophenolate in Living Donor Liver Transplantation: A Systematic Critical Review.

BACKGROUND: The pharmacokinetics (PK) of immunosuppressive agents in living donor liver transplantation (LDLT) recipients are expected to differ from those in deceased donor liver transplantation (DDLT) recipients because of the smaller initial liver volume transplanted and pathophysiological changes during liver regeneration. Consequently, the hepatic metabolism, CYP enzyme activity, and glucuronidation may be reduced. The PK of tacrolimus (metabolized by CYP3A5) and mycophenolate (metabolized through glucuronidation) are expected to be affected early post-LDLT. However, the initial dosing recommendations for post-LDLT remain unclear. PURPOSE: This study aimed to recommend initial dosing approaches for tacrolimus and mycophenolate in LDLT recipients based on available PK data in humans. METHODS: A PubMed search was conducted in March 2025 to identify studies investigating the PK data of immediate-release tacrolimus and mycophenolate in pediatric or adult LDLT recipients. RESULTS: After screening, 8 and 8 articles on tacrolimus and mycophenolates, respectively, met the review criteria. The current literature suggests that LDLT recipients require lower tacrolimus doses than DDLT recipients, particularly in the early post-transplant period. In addition, CYP3A5 polymorphisms in both donors and recipients contribute to interindividual variability in tacrolimus exposure, further complicating tacrolimus management. Studies on mycophenolate use in LDLT recipients are limited, with insufficient evidence to support dose reduction. CONCLUSIONS: Reducing the initial tacrolimus dose in LDLT recipients by 30%-50% compared with that in DDLT recipients would be reasonable while maintaining the same initial dose of mycophenolate between LDLT and DDLT recipients.

Humans↗

PubMed2026

Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0 mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index ≥ 25 kg/m2), and treatment with basal insulin ≤ 40 units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. RESULTS: Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5 kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p < 0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p = 0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). CONCLUSIONS: Once-weekly subcutaneous semaglutide 2.0 mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

Adult↗

PubMed2026

PaNDA: Efficient Optimization of Phylogenetic Diversity in Networks.

Phylogenetic diversity (PD) plays an important role in biodiversity, conservation, and evolutionary studies by measuring the diversity of a set of taxa based on their phylogenetic relationships. In phylogenetic trees, a subset of k taxa with maximum PD can be found by a simple and efficient greedy algorithm. However, this algorithmic tractability is lost when considering phylogenetic networks, which incorporate reticulate evolutionary events such as hybridization and horizontal gene transfer. To address this challenge, we introduce PaNDA (Phylogenetic Network Diversity Algorithms), the first software package and interactive graphical user-interface for exploring, visualizing, and maximizing diversity in phylogenetic networks. PaNDA includes a novel algorithm to find a subset of k taxa with maximum diversity, running in polynomial time for networks of bounded scanwidth, a measure of tree-likeness of a network that grows slower than the well-known level measure. This algorithm considers the variant of PD on networks in which the branch lengths of all paths from the root to the selected taxa contribute towards their diversity. We demonstrate the scalability of this algorithm on simulated networks, successfully analyzing level-15 networks with up to 200 taxa in seconds. We also provide a proof-of-concept analysis using a phylogenetic network on Xiphophorus species, illustrating how the tool can support diversity studies based on real genomic data. The software is easily installable and freely available at https://github.com/nholtgrefe/panda. Additionally, we extend the definition of PD to semi-directed phylogenetic networks, which are mixed graphs increasingly used in phylogenetic analysis to model uncertainty of the root location. We prove that finding a subset of k taxa with maximum diversity remains NP-hard on semi-directed networks, but do present a polynomial-time algorithm for networks with bounded level.

network↗

PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗

PubMed2026

Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin: A Randomized Controlled Trial.

BACKGROUND: Fear of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of community-acquired pneumonia (CAP) frequently leads to empiric vancomycin coverage. Data evaluating the use of MRSA polymerase chain reaction (PCR) nasal swab testing to guide vancomycin de-escalation is limited for patients in the intensive care unit (ICU). METHODS: Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin (STOP-Vanc) is a pragmatic, prospective, single-center, non-blinded randomized trial in which adult ICU patients with suspicion of CAP were randomized 1:1 to receive usual care either with (intervention) or without (control) the addition of MRSA nares PCR testing following ICU admission. The primary outcome was vancomycin-free hours alive, defined as the expected number of hours alive and free of vancomycin use within the first 7 days of trial enrollment as estimated using a longitudinal proportional odds state transition model adjusted for baseline covariates. RESULTS: A total of 277 adult ICU patients were randomized. Methicillin-resistant Staphylococcus aureus PCR nasal swab testing had a negative predictive value (NPV) of 98.9% in the intervention arm. The primary endpoint, vancomycin-free hours alive, was 105.7 in the control arm and 109.7 in the intervention arm (adjusted difference, 4 hours; 95% CI, -9.5-18.2; P = .458). CONCLUSIONS: Despite MRSA PCR nasal swab testing demonstrating a high NPV in this critically ill population, MRSA PCR nasal swab testing did not decrease the duration of vancomycin use or 30-day mortality among ICU patients with suspected CAP. Additional clinician education and antimicrobial stewardship interventions might be needed to reduce vancomycin use in this patient population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT06272994 (STOP-Vanc).

Humans↗

PubMed2026

Optimization of a niosomal formulation for Quercetin delivery: Comparative effects on growth performance, antioxidant and immune responses, and disease resistance against Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

Quercetin (QUR) is a flavonoid with antibacterial and antioxidant properties that has been studied for its effects on fish health and the immune system. Due to the low bioavailability of QUR, the present study was primarily aimed at developing a niosomal formulation of QUR to enhance its bioavailability and therapeutic properties. The performance of niosomal QUR was then compared with that of its free form by evaluating their effects on the growth and immune system of rainbow trout, Oncorhynchus mykiss. For this purpose, an optimal QUR-containing niosome was formulated by testing different proportions of cholesterol, surfactant, and stabilizer, and the niosomes were then added to the fish diet. A QUR-free diet and a diet containing QUR-free niosomes (QFN) were considered control groups. Niosomes prepared at low hydrophilic-lipophilic balance (HLB) values showed higher QUR entrapment efficiency (QUR-EE%) (P < 0.01). An increase in the molar ratio of cholesterol to surfactant significantly reduced QUR-EE% (P < 0.05). A surfactant/cholesterol/stabilizer ratio of 1:1:0.1 increased QUR-EE% (P < 0.05). The particle size of the niosomes was also affected by HLB and the surfactant/cholesterol/stabilizer ratio. Low HLB values resulted in smaller particle sizes (P < 0.01). Furthermore, a surfactant/cholesterol/stabilizer ratio of 1:1:0.1 resulted in the smallest niosomal particle size (P < 0.05). The presence of diacetyl phosphate as the stabilizer in the formulation improved the niosomal zeta potential to -40.55 mV. The optimal niosomal formulation (HLB = 6.6; surfactant/cholesterol/stabilizer ratio of 1:1:0.1) remained stable at 2 °C over 10 days of storage, as the niosomal QUR content and size did not show significant changes during this period (P > 0.01). After preparation of the diets containing the optimal niosomal QUR, fish were fed the experimental diets for two months. QUR, in both niosomal and free forms, resulted in better growth performance than the QUR-free diets (P < 0.01). There were no significant differences in growth performance between the free and niosomal forms of QUR; however, 500 mg/kg QUR showed significantly better growth performance than 250 mg/kg QUR (P < 0.01). Although both the niosomal and free forms of QUR enhanced immune and antioxidant components in the fish, the effects of the niosomal form were more significant (P < 0.01). In addition, QUR in both free and niosomal forms reduced fish mortality after challenge with Streptococcus iniae. In conclusion, the results of this study suggest that the niosomal form of QUR has strong potential for improving the immune system of fish and increasing resistance to S. iniae infection.

Animals↗

PubMed2026

Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 ± 0.14) than the BSS group (1.16 ± 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 ± 4.47 seconds) compared to the BSS group (48.62 ± 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.

Humans↗

PubMed2026

Flux rewiring enables native D-glucosamine production in Escherichia coli.

D-Glucosamine is an industrially important amino sugar used in pharmaceuticals, nutraceuticals, and functional materials, yet its production remains dominated by chemical extraction from chitinous biomass, raising sustainability and allergen concerns. Escherichia coli natively synthesizes D-glucosamine directly from D-glucose through endogenous metabolism, revealing an underutilized amino sugar biosynthetic capability. Building on this native pathway, D-glucosamine production was enhanced through targeted genetic modifications and systematic optimization of nitrogen metabolism and cultivation conditions, reaching 9.2 g L-1 under shake-flask conditions. This work extends a phosphorylation-dephosphorylation strategy previously developed for neutral rare sugars to amino sugar biosynthesis, demonstrating the broader applicability of this metabolic design principle. Phosphatase identity emerged as a key control point for product formation: YbiV was the most effective phosphatase for selective D-glucosamine production, whereas alternative phosphatases redirected flux toward D-sedoheptulose. This enzyme-dependent flux partitioning further enabled tunable co-production of D-glucosamine and D-sedoheptulose. Native amino sugar biosynthesis in E. coli provides a controllable framework for producing chemically distinct sugars through endogenous metabolism and establishes a generalizable strategy for engineering amino sugar and other nitrogen-containing metabolite biosynthesis.

Escherichia coli↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

PubMed2026

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n = 75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p = 0.02 to p < 0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans↗

PubMed2026

Digital healthcare solutions in preoperative care: A systematic review.

OBJECTIVE: Active participation in preoperative anesthesia preparation is crucial to ensure safe and efficient care. Compliance with preoperative instructions improves clinical outcomes, enhances patient satisfaction and optimizes use of healthcare resources. As digital communication becomes increasingly integrated into healthcare, interactive digital tools such as smartphone applications and Short Message Service (SMS) reminders may offer a valuable means of engaging patients in their own care. In this review, we evaluated the role of digital tools in guiding patients during their preoperative care pathway for anesthesia. METHODS: Following registration (CRD420250655119), we conducted a systematic review of studies evaluating the use of smartphone applications or SMS reminders designed to support preoperative preparation for anesthesia or procedural sedation in adult patients undergoing elective procedures. The primary outcome was compliance with preoperative instructions. Secondary outcomes included rate of late cancellations, patient satisfaction and cost-effectiveness. Studies were eligible if they reported at least one of these outcomes. RESULTS: Ten studies (1 RCT and 9 observational studies), including 11501 participants, were identified. Compliance with preoperative instructions was assessed in 8 studies, most of which reported higher compliance in patients receiving digital interventions across multiple instruction domains, although statistical significance was not consistently observed. Evidence suggested a beneficial effect on reducing late cancellations and improving patient satisfaction. However, results varied across study designs, and data on cost-effectiveness were limited. CONCLUSIONS: Digital tools for preoperative anesthesia guidance were associated with higher compliance and showed potential reduction of late cancellations and increase of patient satisfaction. However, the current evidence is predominantly observational and heterogeneous, limiting the strength of conclusions. PRACTICAL IMPLICATIONS: With healthcare systems under pressure, digital technologies may offer a scalable and patient-centered care solution to support preoperative anesthesia preparation. Nonetheless, further high-quality research is needed to evaluate their long-term clinical, economic and equity implications.

Humans↗

PubMed2026

Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes.

Conditional activation of antisense oligonucleotides (ASOs) is a promising strategy for selective suppression of cancer cells without affecting normal cells. In this study, we developed a tripled-stranded ASO (tsASO) that is rendered inactive through complexation with two additional oligonucleotides. The key innovation is the use of partial overlap between the parent ASO and the biomarker sequence, combined with toehold-mediated strand displacement, enabling precise conditional activation. The tsASO effectively triggered RNase H-mediated degradation of DYNC1I2 and DARS1 RNAs exclusively in the presence of the ERBB2 sequence. In cell-free systems, the tsASO demonstrated high cleavage efficiency (up to 81%), comparable to the parent ASO efficiency, with minimal background activity in the absence of the biomarker sequence, validating the concept at the molecular level. However, in cells using lipid-based transfection, the tsASO exhibited nonspecific cytotoxicity that did not correlate with biomarker presence or target gene expression. Detailed analysis showed no clear support for known sequence-driven toxicity mechanisms (CpG/TLR9, G-quadruplexes) in the nonimmune cell lines, suggesting that the primary limitation is intracellular delivery rather than the tsASO design. Future work should focus on optimizing delivery platforms to achieve controlled cellular uptake and biomarker-dependent release, unlocking the therapeutic potential of this conditional gene silencing approach.

Oligonucleotides, Antisense↗

PubMed2026

Three-dimensional porous nano-hydroxyapatite@gelatin composite as efficient adsorbent for uranyl ion removal from low-level radioactive wastewater.

The contamination of water resources by uranyl (UO22+) ions poses significant environmental and health risks, requiring the development of efficient and sustainable remediation strategies. Adsorption-based techniques have emerged as promising approaches in the field of UO22+ removal, but the design of cost-effective, high-capacity, and environmentally friendly adsorbents remains challenging. In this study, a three-dimensional porous nano-hydroxyapatite@gelatin (nHAP@Ge) composite was synthesized through glutaraldehyde cross-linking, combining the structural stability of Ge with the high uranium affinity of nHAP. The optimized nHAP@Ge, with a nHAP:Ge mass ratio of 1:0.5, exhibited exceptional UO22+ removal efficiency (97 %), along with high adsorption capacity (364.03 mg/g). Systematic characterizations using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) methods revealed that the porous structure and surface functional groups (-OH, Ca2+, and PO43-) of the material synergistically contributed to binding UO22+ species. Furthermore, the incorporation of nHAP into the Ge framework resulted in enhanced thermal stability while significantly improving the UO22+ adsorption performance. This work presents a scalable, eco-friendly, and recyclable strategy for the effective treatment of uranium-contaminated water, with potential applications in nuclear wastewater treatment and environmental remediation.

Adsorption↗