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Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The clinical potential of orexin 2 receptor (OX2R) agonism for improving measures of wakefulness and cataplexy in patients with narcolepsy type 1 has been described in a phase 2 study. Here, we aimed to evaluate the safety, tolerability, and efficacy of alixorexton, another oral OX2R agonist, in narcolepsy type 1. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, adult participants (aged 18-70 years) with narcolepsy type 1 were recruited from 46 hospitals and private research centres across the USA, Europe, and Australia. Participants were centrally randomly assigned (1:1:1:1) in blocks of four via an interactive response technology system stratified by region and baseline weekly cataplexy rate (WCR) to receive 4 mg, 6 mg, or 8 mg tablets of alixorexton or placebo once daily for 6 weeks, followed by an optional 7-week open-label extension. Participants had narcolepsy type 1, diagnosed per the International Classification of Sleep Disorders, Third Edition, and confirmed by overnight polysomnography and the Multiple Sleep Latency Test or cerebrospinal hypocretin-1 concentrations. The sponsor, assessors, investigators, and participants were masked during the randomised double-blind treatment period. Efficacy and safety assessments were conducted in participants who received at least one dose of study drug. The primary endpoint was change from baseline to week 6 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT). Safety endpoints included treatment-emergent adverse events. This trial was registered with ClinicalTrials.gov (NCT06358950) and is completed. FINDINGS: Between May 24, 2024, and May 5, 2025, 153 individuals were screened and 92 participants were randomly assigned to receive alixorexton 4 mg (n=23), 6 mg (n=22), 8 mg (n=24), or placebo (n=23). Mean age was 33&#xb7;5 years (SD 12&#xb7;1), 57 (62%) were women, and 35 (38%) were men. At week 6, the observed MSL on the MWT was 2&#xb7;3 min (SD 2&#xb7;7) for placebo, 24&#xb7;0 min (8&#xb7;7) for alixorexton 4 mg, 25&#xb7;9 min (9&#xb7;4) for 6 mg, and 28&#xb7;2 min (11&#xb7;4) for 8 mg. Alixorexton improved MSL on the MWT, with a least-squares mean placebo-corrected change from baseline of 22&#xb7;2 min (95% CI 17&#xb7;2-27&#xb7;2) for alixorexton 4 mg, 24&#xb7;1 min (19&#xb7;0-29&#xb7;1) for 6 mg, and 26&#xb7;0 min (21&#xb7;0-31&#xb7;0) for 8 mg (adjusted p=0&#xb7;0099 for 4 mg, adjusted p<0&#xb7;0001 for 6 mg and 8 mg). Treatment-emergent adverse events occurring in at least 5% of participants given alixorexton and more frequently than those given placebo up to week 6 were pollakiuria (38 [55%]), insomnia (19 [28%]), salivary hypersecretion (17 [25%]), micturition urgency (ten [14%]), blurred vision (ten [14%]), and hyperhidrosis (five [7%]). INTERPRETATION: In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1. FUNDING: Alkermes.

Humans

How to assess different types of abstract concepts in brain disorders: A systematic review.

The clinical evaluation of semantic knowledge has predominantly relied on tools targeting concrete concepts, whereas abstract knowledge has historically received limited attention despite its importance in everyday communication. Only a few instruments have explored the internal subdivision of abstract knowledge, likely due to the intrinsic difficulty of defining specific types of concepts or dimensions, resulting in a fragmented and heterogeneous neuropsychological assessment framework that limits our understanding of this domain. This systematic review examined the tools used to assess various types of abstract concepts in clinical populations. A literature search has been performed on the electronic databases of PubMed and Google Scholar (last update: October 2025). A total of 17 tests is reviewed, differing in the test characteristics, i.e. ranging from automatic to controlled processes and varying in ecological validity, the type of stimuli employed, and the abstract dimensions explored. Most studies have focused on neurodegenerative patients, while comparatively few have examined other clinical conditions. The risk of bias of the reviewed studies was assessed using an ad hoc developed instrument. This review highlights the need for future research to extend investigations to additional abstract domains and clinical populations, while also identifying key challenges related to stimulus selection and the determination of the most appropriate assessment framework.

Humans

Effects of Cognitive Behavioral Couple Therapy With Integrated Mindfulness on Mindful Attention, Depressive Symptoms, and Dyadic Adjustment in Low-Income Couples: A Pilot Randomized Clinical Trial.

Psychosocial distress can exacerbate marital conflict, maladjustment, and mental health vulnerability. This pilot randomized clinical trial examined cognitive-behavioral couple therapy (CBCT) integrated with mindfulness in low-income Brazilian couples (per-capita household income up to one minimum wage). Thirty-four participants (17 heterosexual couples) were randomized (independent computer-generated sequence) to an experimental (n&#x2009;=&#x2009;16) or waitlist control group (n&#x2009;=&#x2009;18). We assessed dyadic adjustment, mindful attention, marital social skills, and depressive symptoms (R-DAS, MAAS, IHSC, BDI-II) at baseline, post-treatment, and 3-month follow-up. The intervention was eight 80-min conjoint sessions plus daily home exercises. Time&#x2009;&#xd7;&#x2009;group effects favored the experimental group for dyadic adjustment, mindful attention, and depressive symptoms (all p&#x2009;<&#x2009;0.001,&#x2009;=&#x2009;0.20-0.37), but not marital social skills (p&#x2009;=&#x2009;0.14). Because two outcomes differed at baseline, effects were confirmed with baseline- and dependence-adjusted sensitivity analyses. These findings provide preliminary evidence that CBCT with mindfulness may benefit disadvantaged couples.

Adult

Efficacy and Safety of the C3 Inhibitor Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of the complement C3 inhibitor pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies reporting pegcetacoplan use in PNH. Outcomes included transfusion-requirement, hemoglobin normalization, mean hemoglobin levels, lactate dehydrogenase normalization, reticulocyte count normalization, and safety endpoints. Pooled proportions with 95% confidence intervals were calculated using random-effects models, and heterogeneity was assessed using the I2 statistic. RESULTS: Five studies comprising 271 patients were included. Transfusion avoidance was observed in 80.6% of patients, with a pooled transfusion-requirement rate of 19.4%. LDH normalization occurred in 68.5% of patients (I2&#x2009;=&#x2009;0%). Hemoglobin normalization was observed in 42.9%, while reticulocyte count normalization reached 66%. Any-grade adverse events occurred in 83.5% of patients, most commonly pyrexia, headache, and dizziness. Serious adverse events occurred in 16.6%, decreasing to 12% after sensitivity analysis. Breakthrough hemolysis was reported in 14.8%, and infections in 17%. CONCLUSION: Pegcetacoplan demonstrates consistent efficacy signals across key hematologic endpoints and an acceptable safety profile, supporting its potential role as an important therapeutic option, particularly in patients with persistent extravascular hemolysis despite C5 inhibition.

Humans

Retention strategies and participant retention rates among prospective longitudinal pregnancy cohorts: a systematic mapping review.

Prospective longitudinal pregnancy cohorts can answer questions about fetal and early life exposures and later health outcomes; however, there are challenges to retaining participants in longitudinal studies, particularly over life transitions like the birth of a child. Optimal methods for retaining participants in longitudinal research are unclear. A systematic mapping review was conducted to identify prospective cohort studies and randomized controlled trials that enrolled pregnant participants and their infants. Data on retention rates and 17 retention strategies was extracted. A random effects meta-analysis generated pooled annual retention rates inversely weighted to the number of baseline participants. Spearman rank coefficients were used to assess correlation between strategy use and retention. A random-effects meta-regression was used to determine if select retention strategies were associated with participant retention. We identified 130 studies, involving 472 022 pregnancies. A downward trend in pooled mean retention rates were observed. Studies utilized an average of 6.8 (SD 3.9) retention strategies. Statistically significant associations were not observed between strategy use and retention rates at follow-up (p&#x202f;>&#x202f;0.05). Prospective studies of pregnant people and their infants used multiple retention strategies. Participant retention rates declined over time, suggesting that additional factors may influence study participation in the postpartum period.

Humans

Targeted variant analysis of feline mediastinal lymphoma using MassARRAY and clinical associations.

Lymphoma is the most commonly diagnosed cancer in cats. This study used the Agena MassARRAY to genotype 40 variants across 17 genes in feline mediastinal lymphoma. These variants have previously been identified in tumors, including T- and B-cell lymphomas, acute and chronic lymphocytic leukemias, and mast cell tumors, in humans, dogs, and cats, using various methods. They were selected based on high prevalence reported in prior oncology studies, potential relevance to targeted therapy, and suitability for multiplex PCR amplification. Pleural fluid samples were collected from 76 cats with mediastinal lymphoma, including 69 domestic shorthairs, two Persians, two Siamese, two Wichienmaat, and one Scottish Fold. The most prevalent variants were found in the BCL2, KIT, STAT3, and ZEB1 genes. Specifically, BCL2 c.83275986G&#xa0;>&#xa0;A and c.83275992G&#xa0;>&#xa0;T were present in 71.1% and 57.9%, respectively. In cats with variant-positive in KIT c.163965724C&#xa0;>&#xa0;CT significantly reduced (11&#xa0;days) compared to wild-type cats (94&#xa0;days) (p&#xa0;<&#xa0;0.001). In cats with variant-positive in STAT3 c.42942437C&#xa0;>&#xa0;CA, resulted in shorter median survival compared to wild-type cats (18&#xa0;days vs. 77&#xa0;days, p&#xa0;=&#xa0;0.006). The findings suggest that the variant panel could be useful for the genomic landscape of feline mediastinal lymphoma and warrant further validation.

Animals

Effects of time-restricted eating on markers of glucose metabolism and regulation in individuals with prediabetes or type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: This systematic review and meta-analysis aimed to investigate the effects of time-restricted eating (TRE) on glucose metabolism and regulation in individuals with prediabetes (fasting blood glucose of 5.6-6.9 mmol/l or HbA1c of 39-47 mmol/mol [5.7-6.4%]) or type 2 diabetes (fasting blood glucose &#x2265;7 mmol/l or HbA1c &#x2265;48 mmol/mol [6.5%]). METHODS: A literature search was performed in MEDLINE, Embase and CENTRAL from inception to 5 August 2025. Moreover, forward and backward citation searches were performed. Eligible studies were RCTs in adults with prediabetes or type 2 diabetes, lasting &#x2265;2 weeks, reporting markers of glucose metabolism and regulation, comparing TRE (&#x2264;12 h eating window) with a non-time-restricted control diet. Studies involving pregnancy, other fasting regimens, or non-peer-reviewed publications were excluded. Data were pooled as weighted mean differences with 95% CIs using random-effects generic inverse variance models in Cochrane Review Manager Web, and results are presented as forest plots. The certainty of evidence was defined using Grading of Recommendations, Assessment, Development and Evaluations methodology, and risk of bias was estimated by using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). RESULTS: Out of 2043 records identified through the database search, as well as 1249 from forward and backward citation searches, ten RCTs including 599 participants were included. The mean length of the studies was 4 months, and the eating windows ranged from 4 to 10 h per day. The pooled meta-analysis showed no overall effect of TRE on HbA1c (-3.33 mmol/mol; 95% CI -6.87, 0.20 (-0.30% points; -0.63, 0.02); p=0.06, moderate certainty). Nevertheless, following stratification by subgroups, TRE resulted in a reduction in HbA1c of 0.93 mmol/mol (-1.70, -0.17 [-0.09% points; -0.16, -0.02]; p=0.02) in individuals with prediabetes but not in individuals with type 2 diabetes (-4.68 mmol/mol; -10.08, 0.72 (-0.43% points; -0.92, 0.07); p=0.09). TRE reduced fasting blood glucose in the pooled analysis (-0.30 mmol/l; -0.53, -0.07; p<0.01, moderate certainty) as well as in the subgroup analyses in individuals with prediabetes (-0.14 mmol/l; -0.27, -0.01; p=0.03) and with type 2 diabetes (-0.48 mmol/l; -0.78, -0.17; p<0.01). Moreover, TRE lowered body weight by 1.6 kg (-2.2, -1.0; p<0.001) in the pooled analysis. The evidence was limited by imprecision arising from wide confidence intervals in some of the included studies, which may be due to small sample sizes. Lastly, the effects of TRE on markers of insulin sensitivity, beta cell function and continuous glucose monitoring measurements were inconclusive. CONCLUSIONS/INTERPRETATION: Moderate-certainty evidence indicates that TRE reduces fasting blood glucose but not HbA1c. The subgroup analyses revealed that TRE improved HbA1c and fasting glucose in individuals with prediabetes and improved fasting glucose in individuals with type 2 diabetes. Future large-scale studies should investigate long-term effects of TRE in prevention and treatment of type 2 diabetes. TRIAL REGISTRATION: PROSPERO CRD42024523591 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Three authors (JS, A-DT, THA) are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, partly funded by a grant from the Novo Nordisk Foundation.

Humans

A homogeneous immunoassay based on AlphaLICA technology for detecting florfenicol residues in animal-derived foods.

Florfenicol (FF), a broad-spectrum amide antibiotic widely used in livestock, poultry, and aquaculture, poses potential threats to food safety and public health due to its residual accumulation. In this study, a novel homogeneous immunoassay based on Amplified Luminescent Proximity Homogeneous Assay (AlphaLICA) technology was developed for the first time for rapid screening of FF residues in milk and egg matrices. By covalently immobilizing the FF-BSA conjugate and goat anti-mouse IgG onto luminescent and photosensitive microspheres, respectively, the method achieved wash-free, homogeneous quantitative detection through a competitive immunoreaction. Under optimized conditions, the assay exhibited a linear range of 0.2-16.2 ng mL-1, with a limit of detection of 9.7 pg mL-1 and a limit of quantification of 183 pg mL-1. The intra- and inter-batch coefficients of variation ranged from 3.08% to 5.70% and 2.44% to 7.09%, respectively. Spike recovery rates in milk and egg matrices ranged from 93.18% to 107.17% (RSD &#x2264; 5.57%). Cross-reactivity with 11 other common antibiotics, including chloramphenicol and thiamphenicol, was below 0.1%, demonstrating excellent specificity. Comparative analysis with a commercial ELISA kit showed high consistency (r2 = 0.9332, p < 0.001). With high sensitivity, strong specificity, simple operation, and a detection time of only 10 min, this method provides a reliable technical platform for high-throughput, rapid monitoring of FF residues in milk and egg matrices.

Journal Article

Lipid metabolism in hepatopancreas and ovaries of the mud crab Scylla paramamosain during vitellogenesis.

Ovarian lipids are essential nutrients that fundamentally determine oocyte and offspring quality, and ultimately affect the reproductive performance of decapod crustaceans. Lipids accumulated in the ovaries during vitellogenesis are mainly derived from the hepatopancreas. However, the molecular mechanisms underlying lipid metabolism in the hepatopancreas and ovaries during vitellogenesis remain largely unclear. In this study, comparative transcriptomic and lipidomic analyses were conducted on the hepatopancreas and ovaries of the mud crab Scylla paramamosain. From early to late vitellogenic stages, 454 lipid species were significantly increased and 17 decreased in abundance in the hepatopancreas, and 609 increased and 23 decreased in abundance in the ovaries. Meanwhile, there were 1481 upregulated and 963 downregulated transcripts in the hepatopancreas, and 3402 upregulated and 1478 downregulated transcripts in the ovaries. Subsequently, KEGG pathway co-enrichment analysis showed that the de novo biosynthesis of glycerophospholipids and glycerolipids was enhanced in the hepatopancreas, with upregulated ALDH, GPAT, plsC, PLPP, FASN, and HSD17B8 transcripts and elevated abundances of PC, PE, PS, PA, PG, DG, and TG species from the early to late vitellogenic stages in mud crabs. In contrast, glycerophospholipid catabolism and conversion were activated in the ovaries, with upregulated PLA2G, LYPLA1, NTE, GPCPD1, PLD_1, PGS1, and CRLS transcripts and elevated abundances of LPC, LPE, LPS species. These findings provide novel insights into the molecular mechanisms of lipid metabolism during vitellogenesis in decapod crustaceans.

Animals

Analyzing salinity tolerance in grass carp (Ctenopharyngodon idella): Insights from genome-wide association study and genomic selection.

Grass carp (Ctenopharyngodon idella) is one of the most widely cultured freshwater fish species globally. However, the expansion of its farming scale faces severe limitation owing to freshwater scarcity; therefore, the development of strains with greater salinity tolerance is key for expanding production using brackish water resources. To investigate the genetic basis of salinity tolerance in grass carp, a genome-wide association study (GWAS) was conducted using 200 individuals representing extreme phenotypes, namely salinity-tolerant and salinity-sensitive groups. In total, 17 single nucleotide polymorphisms (SNPs) related to salinity tolerance were detected, which were distributed across 11 chromosomes. Through gene annotation, 38 candidate genes were obtained from these loci. Enrichment analysis revealed these candidate genes are primarily implicated in key biological processes, including osmotic regulation, energy metabolism, and stress responses. Analyses of different SNP densities revealed that the 5&#xa0;K SNP density panel can balance prediction accuracy and computational efficiency. The BayesA model achieved the highest prediction accuracy under the GWAS_Evenly selection strategy, with substantial reductions in mean absolute error and mean square error. This study reveals the genetic mechanisms of salinity tolerance in grass carp, which might be optimized through genomic selection, and provides insights for selectively breeding new varieties with greater salinity tolerance.

Animals

Does Timing Matter? Age of First Mobile Phone Acquisition and Psychological Outcomes in Middle and Late Adolescence.

The age at which adolescents acquire their first smartphone has decreased markedly in recent years; however, evidence on its long-term effects on psychosocial adjustment remains limited. This study investigated whether age at first mobile phone acquisition is associated with psychosocial functioning in middle and late adolescence, including social integration and competence, emotion regulation difficulties, disordered eating behaviors and problematic social media use (PSMU). The sample comprised 1179 adolescents aged 15-17 years (53.8% female). Linear regression and generalized additive mixed models were used to examine both linear and nonlinear associations, adjusting for age, gender and school clustering. Earlier smartphone acquisition was linearly but weakly associated with greater emotion regulation difficulties, disordered eating and PSMU, even after adjustment for covariates. In contrast, associations with social integration and competence were nonlinear: acquiring a first smartphone between ages 6 and 10 or after age 13 was associated with lower social integration in adolescence, whereas acquisition between ages 11 and 13 was linked to higher social functioning. These findings suggest that the developmental timing of first smartphone access shows a modest association with subsequent psychosocial functioning during middle and late adolescence. Focusing on the timing of access, alongside other demographic and contextual factors, may contribute to a better understanding of digital influences on adolescent well-being.

Humans

Clinical predictors of severe and fatal respiratory syncytial virus infection in adults and the elderly: A retrospective cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as a cause of severe respiratory illness in adults, especially the elderly and those with comorbidities. However, data on outcomes and risk factors for severe disease in this population remain limited. METHODS: We retrospectively analyzed 123 adult patients diagnosed with RSV infection at a tertiary center in Taiwan from 2015 to 2023. Clinical characteristics, laboratory data, detection of other pathogens, clinical course and outcome were reviewed. Multivariable logistic regression identified risk factors for severe RSV infection, including ICU admission and 30-day mortality. RESULTS: The mean age was 55.7 years; 50% were aged &#x2265;60 years and 13% were &#x2265;75 years. ICU admission occurred in 17%, with significant associations to viral coinfection and elevated C-reactive protein (CRP). Thirty-day mortality was 13%, and overall in-hospital mortality was 18%, all among patients with comorbidities. Independent predictors of 30-day mortality included late elderly (aOR 24.2, p&#x202f;=&#x202f;0.03), high CRP > 11.5&#x202f;mg/dL (aOR 16.4, p&#x202f;=&#x202f;0.005) and thrombocytopenia < 34,103/&#x3bc;L (aOR 11.4, p&#x202f;=&#x202f;0.01). CONCLUSION: Advanced age (&#x2265;75 years), high CRP, and severe thrombocytopenia are key predictors of mortality in adults RSV patients. These findings highlight the need for targeted prevention strategies, including vaccination, in high-risk populations.

Co-infection

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal&#x202f;=&#x202f;21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

Humans

Effects of exercise snacking on neuromuscular performance in insufficiently active adults: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of exercise snacking (ES) on neuromuscular performance in insufficiently active adults. METHODS: Six databases were searched from inception to July 17, 2026. Randomized controlled trials and non-randomized studies of interventions involving insufficiently active adults undertaking ES interventions were included. Outcomes were functional performance, muscular strength, and muscular power. A three-level random-effects meta-analysis was performed. Risk of bias was assessed with RoB 2 or ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Nine studies (13 reports) involving 313 participants were included. In the primary three-level model, ES showed a small positive overall effect on neuromuscular performance (g = 0.37, 95% CI 0.16-0.58, p&#x202f;=&#x202f;0.001), which remained supported under trial-clustered robust inference with small-sample adjustment. Domain-specific estimates for muscular power/velocity, functional performance, and muscular strength were positive but imprecise and were not statistically supported after small-sample robust adjustment. Robust moderator tests provided no evidence of between-subgroup differences, and the certainty of evidence was low for all outcomes. CONCLUSION: Current low-certainty evidence suggests that ES may produce a small improvement in overall neuromuscular performance. However, domain-specific effects remain uncertain because of the limited number of independent trials, and the overall prediction interval crossed zero, indicating uncertainty across future populations and settings. Larger, preregistered randomized controlled trials are needed to confirm these preliminary findings.

Adult

Urban stormwater infrastructure as a microplastic superhighway: a critical review of transport dynamics, modelling, and mitigation across pavements and drainage networks.

This review examines the transport, fate, modelling, and mitigation of Microplastics (MPs) in urban stormwater infrastructure, with emphasis on pavements, runoff pathways, micro-drainage, and macro-drainage systems. Following a systematic review approach, more than 1000 records were screened and approximately 50 core studies were retained when they addressed urban stormwater or drainage-related MP transport with adequate methodological reporting; marine-only studies and biological-effect studies without direct relevance to transport processes were excluded. The evidence shows that stormwater systems function not merely as passive conduits but as dynamic reactive transport systems with temporary storage, where particle mobilisation, sedimentation, resuspension, and temporary retention regulate MP export. Road surfaces, especially high-traffic areas, are major reservoirs of tyre wear, road-marking, atmospheric, and litter-derived particles that are rapidly mobilised during rainfall. Conventional grab sampling may underestimate MP loads, which in some cases exceed treated wastewater effluent loads by up to six-fold. Drainage structures such as manholes can immobilise up to 17.3% of near-neutrally buoyant particles, while biofouling and aggregation may shift buoyant polymers from wash-load to bedload. Mitigation systems, including permeable pavements, bioretention, wetlands, and technical inserts, can achieve high removal of coarse MPs, but performance declines for fine particles below 100&#xa0;&#xb5;m. The review highlights the need for standardised flow-proportional sampling, physically informed modelling, and treatment-train strategies targeting both surface sources and in-network storage.

Microplastics

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged &#x2265;21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for &#x2265;60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10&#xb7;0 months (IQR 4&#xb7;6-17&#xb7;2); median follow-up for progression-free survival was 11&#xb7;0 months (IQR 4&#xb7;8-18&#xb7;4) for STRIDE plus lenvatinib plus TACE and 8&#xb7;3 months (4&#xb7;1-15&#xb7;5) for TACE. Median progression-free survival was 13&#xb7;0 months (95% CI 12&#xb7;2-16&#xb7;7) for STRIDE plus lenvatinib plus TACE versus 9&#xb7;8 months (8&#xb7;0-11&#xb7;4) for TACE (HR 0&#xb7;70 [95% CI 0&#xb7;57-0&#xb7;86]; p=0&#xb7;0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24&#xb7;6 months (IQR 16&#xb7;5-31&#xb7;5) for STRIDE plus lenvatinib plus TACE and 22&#xb7;9 months (14&#xb7;9-30&#xb7;2) for TACE, median overall survival was 39&#xb7;5 months (95% CI 34&#xb7;1-not reached) for STRIDE plus lenvatinib plus TACE and 34&#xb7;7 months (28&#xb7;8-not reached) for TACE (HR 0&#xb7;84 [95% CI 0&#xb7;65-1&#xb7;09]; p=0&#xb7;18). At this data cutoff, median progression-free survival was 12&#xb7;9 months (95% CI 10&#xb7;2-15&#xb7;9) for STRIDE plus TACE and 8&#xb7;1 months (6&#xb7;5-10&#xb7;2) for the first 175 participants randomised to TACE (HR 0&#xb7;71 [95% CI 0&#xb7;56-0&#xb7;91]), with median follow-up of 10&#xb7;3 months (IQR 4&#xb7;6-23&#xb7;7) for STRIDE plus TACE and 7&#xb7;7 months (3&#xb7;0-18&#xb7;5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult

Plant species identification by genome skimming across the vascular plant tree of life.

Accurate species identification is essential for biodiversity conservation and sustainable use, yet standard plant DNA barcoding often fails to achieve species-level resolution. We present a large-scale empirical evaluation of genome skimming as a tool to improve plant species discrimination. Using standardised data from 1969 individuals representing 475 species from 32 genera across major lineages of the vascular plant tree of life, we compare conventional plastid + internal transcribed spacer (ITS) barcodes with genome skimming approaches. Standard barcoding using rbcL, matK, trnH-psbA and ITS resolved about half of species (49.3%), with six genera showing <&#x2009;25% species discrimination. By contrast, genome skimming enabled the recovery of complete plastid genomes, yielding 57.6% species discrimination. It also generated sufficient nuclear genomic data for additional resolution from k-mer analysis, achieving 66.8% species discrimination - an average gain of 17.5% over standard barcodes - while eliminating cases of extreme failure (<&#x2009;25% resolution). The recovery of complete plastomes and ribosomal DNAs from genome skims also ensures backward compatibility with existing barcode datasets. Our results demonstrate that genome skimming provides data that substantially improves species-level resolution across diverse plant lineages and offers a scalable, high-throughput approach for building comprehensive reference resources to support global biodiversity initiatives.

DNA Barcoding, Taxonomic