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PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗

PubMed2026

Conserved host-exclusive oligonucleotide motifs enriched in pathogenic genes of human oncogenic viruses.

Comparative viral genomics can reveal sequence-level constraints influencing virus-host interactions. Relative minimal absent words (rMAWs) are short oligonucleotide motifs present in viral genomes but completely absent from the host, potentially reflecting selective pressures related to host adaptation and immune evasion. Using the EAGLE algorithm and the GRCh38 human reference genome, we systematically screened for prevalent rMAWs (prMAWs) across six major human oncogenic viruses: Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), human T-cell leukemia virus type 1 (HTLV-1), and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). highly conserved 11- and 12-bp prMAWs were identified in EBV, HBV, HTLV-1, and HHV-8/KSHV, with sequence prevalences ranging from 91.5% to 97.9%. Conversely, no short prMAWs were detected in HCV or HPV, likely reflecting differences in genome architecture, mutation rates, and long-term host adaptation to the human host. Importantly, the identified host-exclusive motifs exhibited non-random genomic distribution and were preferentially embedded within viral genes central to replication, persistence, immune modulation, and oncogenesis, including EBNA-1 (EBV), HBx (HBV), Tax-associated regions (HTLV-1), and lytic replication genes of HHV-8/KSHV. Notably, all detected prMAWs were enriched in GC nucleotides and exhibited marked CpG over-representation, suggesting sequence constraints associated with epigenetic regulation and viral persistence. Collectively, these highly conserved, host-exclusive signatures offer promising, candidates for sequence-directed approaches in the diagnosis, monitoring, and investigation of virus-associated cancers.

Humans↗

PubMed2025

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin ≤ 18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin ≤ 18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the ≥ 11- ≤ 18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans↗

PubMed2026

Sexual selection purges mutation load, but not overall genetic diversity, decreasing vulnerability to extinction.

Theory suggests sexual selection will enhance population viability by purging deleterious alleles. However, direct genomic evidence for this fundamental idea is scarce and contradictory. We combined long-term experimental evolution with whole-genome resequencing to directly test how sexual selection affects mutation load, genomic divergence, and extinction risk in small populations (maximum Ne = 40) of Tribolium castaneum. After 156 generations, populations evolving under strong sexual selection carried substantially fewer deleterious alleles than populations under weak sexual selection, based on both individual-level estimates of missense and nonsense variants and population-level Rxy analyses, indicating more efficient purging of deleterious alleles. In contrast, nucleotide diversity and runs of homozygosity were similar across treatments, indicating that purging acted most strongly on deleterious variation, and that reduced mutation load in these small populations under strong sexual selection was not explained by demographic effects. Importantly, population-level mutation load estimates best explained extinction risk under inbreeding, directly linking sexual selection to purging and population viability. Genome scans of high and low sexual selection populations revealed peaks of divergence, which included genes involved in courtship, sex discrimination, and seminal fluid proteins. Our results provide direct genomic evidence that sexual selection can reduce mutation load without eroding standing genetic diversity and thus adaptive potential, while driving adaptive divergence in reproductive traits. This beneficial purging may help explain the widespread prevalence of sexual reproduction in nature despite inherent costs and have important ramifications as to how we manage populations of conservation concern.

Animals↗

PubMed2026

Rational design of high-productivity perfusion processes for CHO Cells: From growth inhibitory strategies to model-driven optimization.

While perfusion culture for Chinese hamster ovary (CHO) cells offers advantages such as continuous operation and flexibility, it suffers from product loss through cell bleeding and difficulties in reaching high productivity due to sustained rapid cell growth. Growth inhibitory strategies are widely used to enhance productivity in fed‑batch processes; however, their practical implementation and comparative effectiveness in perfusion processes remain insufficiently explored. Meanwhile, process development often relies on costly trial‑and‑error approaches. Here, we systematically compared three growth inhibitory strategies in perfusion culture-low cell‑specific perfusion rate (CSPR), sodium butyrate, and mild hypothermia-with respect to cell growth, metabolism, productivity, and product quality. Genome‑scale metabolic flux sampling analysis revealed that low‑CSPR and sodium butyrate induce a convergent up‑regulation of energy metabolism, correlating with greater gains in specific productivity (qp). Building on this insight, we developed a growth‑kinetic model for the combined low‑CSPR + butyrate strategy, incorporating parameter uncertainty. This model‑guided framework enabled the rational design of two distinct high‑productivity perfusion processes: a sustained mode that achieved robust long‑term stability alongside substantial productivity gains, and a high‑intensity mode that pushed qp and daily volumetric titer to their maxima, with increases of up to 108.94% and 190.36%, respectively, in a model CHO cell line with a moderate baseline productivity. Our study provides a proof‑of‑concept framework for perfusion intensification, from strategy selection to rational process design.

Animals↗

PubMed2026

Assessment of temporomandibular joint space changes after orthognathic surgery in skeletal malocclusion patients: a systematic review.

PURPOSE: To interpret postoperative changes in temporomandibular joint (TMJ) joint space dimensions and condylar position following orthognathic surgery in patients with skeletal malocclusions, and to determine whether reported alterations represent clinically meaningful displacement or physiological adaptive remodeling. MATERIALS AND METHODS: A comprehensive search of PubMed, SCOPUS, Web of Science, EBSCOhost, and Cochrane Library was performed to assess pre- and postoperative TMJ changes using three-dimensional imaging. Joint spaces including anterior (AJS), superior (SJS), and posterior (PJS) and condylar morphology were evaluated. Methodological quality was appraised using the Joanna Briggs Institute (JBI) checklist. Due to methodological and clinical heterogeneity, findings were synthesized narratively with attention to malocclusion type and surgical movement. RESULTS: A total of 16 studies consisting 628 patients undergoing BSSO, Le Fort I osteotomy, vertical ramus osteotomy, or bimaxillary surgery were included. Most studies reported minor, adaptive postoperative changes in AJS, SJS, and PJS. Class II patients showed more consistent increases in AJS/SJS, whereas Class III patients demonstrated variable posterior or anterior remodelling depending on surgical movement. Volumetric analyses revealed region-specific adaptations without significant condylar displacement. Postoperative temporomandibular disorder symptoms were infrequent, and no consistent evidence supported detrimental TMJ effects attributable to surgery. CONCLUSION: Postoperative TMJ joint space changes after orthognathic surgery primarily represent physiological adaptive remodeling rather than pathological condylar displacement, with reported variability driven by malocclusion type, surgical movement, fixation method, and imaging protocol. Recognizing these predictable patterns is essential to prevent overinterpretation of postoperative imaging and to improve clinical assessment through standardized three-dimensional and long-term evaluation strategies.

Humans↗

PubMed2026

Meta-PseU: A meta-classifier for robust prediction of RNA pseudouridine modification sites from long sequences.

BACKGROUND AND OBJECTIVES: Pseudouridine (Ψ) represents one of the most abundant and conserved RNA modifications. Ψ provides an additional hydrogen-bond donor that enhances RNA structural stability and modulates translation. It participates in diverse biological processes, including RNA-protein interactions, splicing, translational control, and stress responses. Aberrant pseudouridylation is implicated in cancer, neurodegenerative disorders, and autoimmune diseases. Despite its biological importance, experimental identification of Ψ sites remains time-consuming and costly, limiting the feasibility of transcriptome-wide profiling. Computational approaches have therefore become essential complements to experimental techniques. However, state-of-the-art machine-learning and deep-learning predictors often suffer from limited generalizability due to small training datasets. To overcome these issues, we aim at constructing new long-sequence datasets and developing a novel Ψ site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA Ψ-site prediction. The Ψ modification sites in RMBase 3.0 were mapped to the reference genomes across three species of human, mouse, and yeast, and the RNA sequences with a length of 201 were generated by extending the upstream and downstream from the mapped, central sites. To eliminate sequence redundancy, the sequences were clustered using CD-HIT with a 70% sequence identity threshold. We developed Meta-PseU, a logistic regression-based meta-classifier that considered 118 machine learning and deep learning classifiers. The datasets and programs are freely accessible at https://github.com/kuratahiroyuki/MetaPseU. RESULTS: By optimizing model configuration, we proposed the Meta-PseU model stacking 32 machine learning and deep learning classifiers out of 118 classifiers. Meta-PseU substantially improved model generalizability, overcoming a key limitation of existing approaches. It greatly outperformed state-of-the-art predictors and achieved increasing accuracy with increasing sequence length. CONCLUSIONS: Long-sequence datasets were newly constructed as benchmarks for RNA Ψ-site prediction. Meta-PseU offers a new framework for robust Ψ-site identification by using long sequences.

Pseudouridine↗

PubMed2026

Hip Arthroscopy-Assisted Management of Pipkin Types I and II Femoral Head Fracture-Dislocations: Mid-Term Clinical and Radiographic Outcomes.

OBJECTIVES: Hip arthroscopy-assisted surgery has been proposed as a minimally invasive option for femoral head fractures; however, evidence with mid-term follow-up remains limited. This study aimed to evaluate the clinical and radiographic outcomes of arthroscopy-assisted management for Pipkin Types I and II femoral head fracture-dislocations with a minimum follow-up of 5 years. METHODS: This retrospective study included 23 consecutive adults (19 Pipkin I and 4 Pipkin II) treated with hip arthroscopy-assisted fragment excision or internal fixation between March 2013 and January 2020. Preoperative computed tomography was used for surgical planning, and fixation was placed with arthroscopic headless screws. Clinical outcomes were assessed using the Harris Hip Score (HHS) and Thompson-Epstein (T-E) criteria. Radiographic evaluation included avascular necrosis (AVN), heterotopic ossification (HO; Brooker), osteoarthritis (OA; Tönnis), and fracture reduction quality (Matta's criteria). Group comparisons were evaluated using independent samples t-tests, Mann-Whitney U tests, and Fisher's exact test. The mean follow-up was 86.2 ± 21.2 months. RESULTS: The cohort consisted of 19 males and 4 females with a mean age of 28.7 ± 9.9 years. Fifteen patients underwent fixation and eight underwent excision. The final mean HHS was 98.3 ± 1.9, with 21 patients (91%) achieving excellent and 2 (9%) good T-E criteria. There were no significant differences between the fixation and excision groups in demographic characteristics, operative time, or functional outcomes (all p > 0.05); however, hospital stay was significantly shorter in the excision group (2.9 ± 0.6 vs. 5.5 ± 4.6 days, p = 0.028). In the fixation group, mean maximal displacement improved from 7.6 mm preoperatively to 2.6 mm postoperatively, with anatomic reduction achieved in 6 cases (40%), imperfect in 6 (40%), and poor in 3 (20%). Patients with Pipkin Type I fractures had significantly higher HHS than those with Type II fractures (98.7 ± 1.7 vs. 96.0 ± 0.8, p = 0.018). Complications were rare, with one case of Brooker Grade I HO and one case of mild OA. No AVN or total hip arthroplasty occurred during the follow-up. CONCLUSIONS: Hip arthroscopy-assisted management of selected Pipkin Type I and II femoral head fractures yields excellent mid-term clinical outcomes with acceptable radiographic reduction and a low complication rate. This minimally invasive technique represents a viable alternative in appropriately selected patients when fragment characteristics and surgical expertise permit.

Humans↗

PubMed2026

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB↗

PubMed2026

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12 months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade ≥ 2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade ≥ 3 pulmonary adverse events following SBRT and in overall grade ≥ 2 oesophageal adverse events among patients with clinical stage I-II and those aged >70 years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes↗

PubMed2026

Integration of Clinical Case Scenarios With Anatomical Dissection Teaching-Is Recall Improved Among Medical Students?

BACKGROUND: There is ongoing debate about how best to deliver anatomy teaching in a modern medical curriculum. Some studies suggest that the separation of basic sciences and clinical teaching can impact students' confidence in anatomy, which has potential long-term implications on their medical career. This suggests new pedagogic approaches to improve anatomy teaching may be beneficial. This study aimed to establish if integrating a clinical case into anatomy practical classes would improve students' anatomy recall compared to anatomy teaching alone. APPROACH: A ten minute clinical scenario was developed, which focused on the typical history, examination, investigations and management of a hip fracture patient. Medical students (n = 220) currently studying lower limb anatomy were randomised by pre-assigned anatomy groups to become intervention or control. In the intervention group, students received the clinical case teaching, followed by their anatomy session. In the control group, students attended the anatomy session. Students in both groups were then assessed on hip anatomy. The intervention group also gave their perception of the clinical case. EVALUATION: This study showed that participants who received integrated teaching performed significantly better in the anatomy recall test (3.64 SD ± 0.574) than whose who had anatomy teaching only (1.95 SD ± 0.994) (chi2 = 185.51, p < 0.00001). Most participants (93.5%; 101/108) strongly agreed/agreed that integrating clinical cases into anatomy teaching benefited their learning. IMPLICATIONS: These results suggest that students' anatomy recall may be improved by integrating clinical cases and anatomy teaching. It also suggests that students found this approach beneficial for their learning.

Humans↗

PubMed2026

Upscaling Genotyping by Amplicon Sequencing With GBAS-GUI.

Genotyping by amplicon sequencing (GBAS) is a relatively low-cost approach for generating genotypic data compared with established genomic methods, making it highly scalable and particularly suitable for large-scale genetic monitoring projects. However, most existing analytical pipelines are either marker-specific, insufficiently scalable, or lacking efficient data management systems for the long-term integration of genotypic information, limiting the full potential of GBAS. Here, we address this gap by introducing GBAS-GUI (https://github.com/sonnenbe-dot/GBAS-GUI), a pipeline capable of generating GBAS-based genotypic data for a wide variety of loci at scale. GBAS-GUI integrates a graphical user interface with multiple checkpoints to improve accessibility and robustness. It implements multiprocessing architecture and a relational database that links genotypic data with associated sample metadata to enhance scalability and data management. The pipeline further enables marker screening through automated calculation of polymorphism information content (PIC) and implements a strategy to recover homologous genotypic information from paralogous loci with non-overlapping amplicon length ranges. Using multiple empirical datasets, we demonstrate substantial improvements in processing speed, database management and handling artefacts related to co-amplification of unspecific regions and duplicates of the same genomic region. We further show that incorporating the full sequence information captured by an amplicon increases marker information content beyond what is achievable with length-based genotyping alone and expands the analytical versatility of GBAS. Overall, GBAS-GUI provides a robust, scalable and versatile framework that unlocks the potential of GBAS for large-scale population genetic and phylogeographic studies.

Genotyping Techniques↗

PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2026

Operationalizing Local Ecological Knowledge for Aquatic Biodiversity Conservation: A Systematic Review and Management Framework.

Effective conservation and management of aquatic biodiversity is severely constrained by the absence of long-term ecological data in small-scale, tropical, and data-poor fisheries, where roughly one-quarter to one-third of freshwater fish species and 37.5% of elasmobranchs are threatened with extinction once Data Deficient species are accounted for. Conventional monitoring and stock-assessment tools are often financially and technically inaccessible in these systems, leaving managers without the evidence needed to prioritize conservation action or implement precautionary governance. Local Ecological Knowledge (LEK) is a largely underutilized resource for natural resource management that can provide temporal depth, spatial resolution, and species-specific ecological insights unavailable from scientific records. We conducted a systematic review and bibliometric synthesis of 60 peer-reviewed studies (1997-2025) applying LEK to assess fish conservation status, examining how, where, and through what methods this knowledge has been used. Our analysis identifies four complementary pathways through which LEK informs conservation management: reconstructing multi-decadal population changes, documenting spatial contraction and habitat loss, detecting extreme rarity and local extirpation, and characterizing intrinsic sensitivity to exploitation based on life-history traits. Despite growing methodological rigor, freshwater systems and African fisheries remain critically underrepresented, and formal integration of LEK into fisheries governance and biodiversity assessment remains the exception rather than the rule. We propose a practical three-stage framework to operationalize LEK within existing management and conservation systems. Recognizing fishing communities as legitimate co-producers of ecological knowledge is both scientifically necessary and an equity imperative for achieving global biodiversity commitments under the Kunming-Montreal Global Biodiversity Framework.

Biodiversity↗

PubMed2026

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans↗

PubMed2026

Ultrasound-guided high-voltage vs conventional pulsed radiofrequency in elderly cervical radiculopathy: A randomized controlled trial.

BACKGROUND: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. OBJECTIVES: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. METHODS: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60-85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature ≤42°C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (ΔNRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. RESULTS: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46-2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11-10.83, P=0.004). Responder rates (≥50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1-3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). CONCLUSION: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control ≤42°C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.

Humans↗

PubMed2026

The effects of cold temperature on the development, microbiome, and transcriptome of the sea anemone Nematostella vectensis.

Thermal conditions impact essentially all aspects of the physiology for ectotherms. While the effects of high temperatures have been widely studied, cold temperature effects on aquatic invertebrates and their microbial communities have been poorly characterized. To determine the diverse effects of exposure to cold temperatures, we assessed acute and long-term impacts of ecologically relevant low temperatures on the development, microbiome, and gene expression of the sea anemone Nematostella vectensis. Two hours post fertilization, embryos were exposed to temperatures from 4°C to 35°C and development rate to the juvenile stage was quantified. We found temperature impacts the development rate of embryos, where lower temperatures extended development time and resulted in mortality below 10°C. For both microbiome and host transcriptomic responses, anemones were held at 20°C, 10°C, and 0°C and compared at 24 hours and 7 days. Extended exposures to colder temperatures caused restructuring of the host-associated microbiome, with the loss of common taxonomic groups from the class Bacteroidia and Bacilli. Lastly, cold stress induced significant changes in gene expression, which were more pronounced at the 10°C than 0°C but showed little change over time in each temperature. Interestingly, expression of genes associated with innate immunity were among the most differentially expressed genes including heat shock proteins and innate immune genes providing a potential host-imposed mechanism to explain the shift in the microbiome. Overall, cold temperatures have broad effects on many facets of this sea anemone and its microbial community and indicate the importance of cold temperature events when characterizing how ectotherms acclimate to thermal variation.

Animals↗

PubMed2026

Understanding Suicide through Coroners' Narratives: implications for primary care from a mixed‑methods study of 157 Coroners' reports.

Suicide is a major public health concern, and general practice is often a recent point of contact before death. While mental illness is well recognised, the broader social and contextual factors influencing suicide risk remain under-reported in primary care and epidemiological research Aim To describe the demographic, clinical, and psychosocial characteristics of individuals who died by suicide, integrating coronial quantitative data with qualitative narrative accounts to identify implications for primary/ secondary care and public health. Design and setting Explanatory sequential mixed‑methods study of 157 consecutive deaths by suicide recorded by coroners (2018-19) across five English local authorities. Method Demographic, clinical, and social data were extracted from coroners' records and summarised descriptively. Narrative case summaries were coded and analysed thematically to identify contextual, relational, and service factors preceding death. Results Of 157 individuals: 79% were male; 65% lived in the most deprived IMD quintile; 85% had a diagnosed mental health condition; 62% had a long‑term physical illness; 41% had a previous suicide attempt. About half consulted a GP in the preceding three months; mental health featured in about half of those consultations. Common stressors were relationship breakdown (37.2%), housing instability (22.1%), and work pressures (18.2%). Seven interlinked themes were identified: Mental health; Alcohol/Substance use, Physical health; Social connectedness; Life course trauma, Socioeconomic and Structural Vulnerability; Healthcare access. Service transitions were key vulnerability points Conclusion Coroners' records offer important insights into the complex circumstances preceding suicide and highlight opportunities for GPs to recognise intersectional complexity and support integrated, cross-sector suicide prevention approaches.

General Practice↗