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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

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

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

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

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans

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

Second-Generation ELZA-sub400 Protocol: Individualized High-Fluence Cross-Linking for Ultra-Thin Keratoconus Corneas.

PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospective, single-center, consecutive interventional case series. METHODS: Twenty-nine eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and a post-soak intraoperative thinnest stromal thickness <400 &#xb5;m were included. After epithelial removal and riboflavin soaking, continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm&#xb2; was delivered with total fluence titrated up to 10 J/cm&#xb2; based on intraoperative ultrasound pachymetry and a previously published nomogram targeting an uncross-linked stromal margin of approximately 70 &#xb5;m above the endothelium. Outcomes were assessed at baseline and up to 12 months using corrected distance visual acuity (CDVA) and corneal parameters measured using Scheimpflug tomography and anterior segment OCT (AS-OCT) with Placido-based topography. The main outcome measure was the proportion of eyes without progression at 12 months, defined as <1.0 D increase in maximum keratometry (Kmax). Secondary outcomes included changes in CDVA, refraction, Kmax, stromal thickness, demarcation line depth, densitometry, and safety parameters. RESULTS: At 12 months, 22/29 eyes (76%; 95% CI, 57.9%-87.8%) met the nonprogression criterion. Mean change in Kmax was -0.77 &#xb1; 5.10 D (95% CI, -2.71 to 1.17; P = .418). Mean demarcation line-to-anterior stroma distance was 205 &#xb1; 64 &#xb5;m (95% CI, 180.7-229.3), and demarcation line-to-endothelium distance was 64 &#xb5;m (IQR, 49-152). All demarcation lines remained within the stromal layer; 15/29 eyes (51.7%) had a demarcation line located &#x2264;70 &#xb5;m from the endothelium. Median CDVA changed from 0.10 to 0.32 logMAR (P = .142). Minimum stromal thickness showed a median change of -4.0 &#xb5;m (P = .309). No significant change was observed in densitometry, and no eye developed deep stromal haze or endothelial decompensation. CONCLUSIONS: Second-generation ELZA-sub400 CXL halted ectasia progression in 76% of ultrathin corneas at 12 months and was associated with an acceptable short-term safety profile, including stromal-confined demarcation line formation and no observed endothelial decompensation. The numerical decline in spectacle CDVA observed in this severely affected cohort did not reach statistical significance but is clinically important and warrants confirmation in larger prospective studies.

Humans

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

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

Humans

Late hiatal hernia after Roux-en-Y gastric bypass: a systematic review.

Obesity is a global public health issue. This condition is linked to gastroesophageal reflux disease (GERD) and hiatal hernia (HH), both of which are exacerbated by increased intra-abdominal pressure. Roux-en-Y gastric bypass (RYGB) is one of the most widely performed techniques for treating obesity and is considered a versatile option suitable for most patients. The development of a symptomatic HH and pouch migration can lead to various symptoms and complications. PubMed, EMBASE, and Cochrane Central were searched for studies with late HH after RYGB. We pooled outcomes for symptom resolution. Secondary outcomes were recurrence rate and operation characteristics (mesh use, cruroplasty, gastropexy, reoperation, length of stay, and operative time). A meta-analysis could not be conducted due to significant heterogeneity in HH. HH following RYGB presents with GERD (39-93.6%), obstructive symptoms (29%-88%), and abdominal pain (28.6%-71%). Diagnostic methods include endoscopy, computed tomography scans, and upper gastrointestinal series. Surgical management varies, with primary cruroplasty being the most common approach, sometimes incorporating mesh or fundoplication. Postoperative symptom resolution rates range from 42.9% to 100%, with HH recurrence occurring in 5%-6.54% of cases. Follow-up durations varied, showing improvement in most patients, though some continued to experience reflux and dysphagia HH contributes to obstructive and reflux symptoms, with contrast-enhanced imaging offering the highest diagnostic accuracy. Bioabsorbable mesh may reduce recurrence, highlighting the need for long-term monitoring.

Humans

Nimodipine in animal models of demyelination relevant to multiple sclerosis: a systematic review.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in which axonal injury, neuronal death, and demyelination occur. Treatment for MS relapses remains limited, which alleviates acute loss of function but has no impact on long-term disability. This study aimed to perform a systematic review of the effects of nimodipine on experimental demyelination models, including experimental autoimmune encephalomyelitis (EAE) and Cuprizone models in rodents. METHODS: This study was conducted following the PRISMA statement. A systematic search was performed in PubMed, Scopus, the Cochrane Library, and Google Scholar. The primary outcome was EAE clinical disease severity (peak clinical score and/or cumulative disease burden). Secondary outcomes included relapse activity (when reported), histological myelin outcomes, oligodendrocyte lineage markers, neuroaxonal injury markers, and inflammatory readouts. Risk of bias was assessed using the SYRCLE tool. RESULTS: Out of 4660 results, 5 studies were included in the systematic review (four EAE studies and one cuprizone model). Nimodipine was administered using heterogeneous regimens (oral, intravenous, intraperitoneal, subcutaneous, or osmotic pump delivery; 1-30&#xa0;mg/kg/day). The included studies reported the variable effects of nimodipine on relapse-related outcomes, myelination, inflammatory processes, and neuroprotection in the EAE model of MS. Across EAE studies, nimodipine generally reduced clinical disease severity or cumulative burden, although relapse-related outcomes were inconsistent. CONCLUSIONS: Preclinical evidence suggests that nimodipine may attenuate disease severity and demyelination and may promote repair-related processes in rodent models relevant to MS. However, to evaluate the clinical applicability of nimodipine in MS patients, well-powered, transparently reported preclinical replication and early-phase clinical studies are required before clinical translation.

Animals

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&#x2009;=&#x2009;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 &#xb1; 0.574) than whose who had anatomy teaching only (1.95 SD &#xb1; 0.994) (chi2&#x2009;=&#x2009;185.51, p&#x2009;<&#x2009;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

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

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

Effects of extended problem-based learning interventions on undergraduate nursing education: A systematic review.

OBJECTIVE: Exploring the effects of long-term PBL (problem-based learning) intervention on undergraduate nursing students. METHODS: The article retrieved literature from CINAHL Complete, Academic Search Complete, Web of Science, PubMed, EMBASE, OVID, and Cochrane Library up to January 2025. Studies had to meet all of these criteria: (1) They used a randomized controlled trial (RCT) and quasi-experimental design. (2) The PBL pedagogy intervention lasted 4&#xa0;weeks or longer. (3) The participants were undergraduate nursing students. (4) They reported primary outcomes. These included critical thinking, problem-solving skills and self-directed learning. Two researchers screened articles, extracted data, and assessed quality independently using blinding. They used Cochrane ROB2 for RCTs and ROBINS-I for quasi-experimental studies to judge bias risk. Meta-analysis was performed using RevMan 5.4 software. For continuous variables, standardized mean difference (SMD) and 95% confidence interval were calculated. Heterogeneity was assessed by I2 statistic. When I2&#xa0;>&#xa0;50%, sensitivity analysis was conducted. The source of heterogeneity was explored by excluding studies one by one. The primary outcomes included standardized critical thinking, problem-solving, and self-directed learning assessment results. RESULTS: A total of 11 randomized controlled trials and quasi-experimental studies were retrieved and included for meta-analysis. The experimental group significantly outperformed the control group in critical thinking, problem-solving, and self-directed learning, with differences being statistically significant (P&#xa0;&#x2264;&#xa0;0.05). However, high heterogeneity was observed. After sensitivity analysis, the heterogeneity was reduced and the results remained statistically significant, indicating that the findings were not solely dependent on the excluded studies.

Problem-Based Learning

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

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&#xb0;C to 35&#xb0;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&#xb0;C. For both microbiome and host transcriptomic responses, anemones were held at 20&#xb0;C, 10&#xb0;C, and 0&#xb0;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&#xb0;C than 0&#xb0;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

HYPNOSA: Study protocol for a prospective observational cohort of patients with obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a common chronic disease that affects more than 20% of the adult population. One of the most frequent and characteristic symptoms of OSA is excessive daytime sleepiness (EDS). This symptom is typically treated in patients with OSA with the application of continuous positive airway pressure (CPAP), the gold-standard treatment for this disease. In some patients who are adequately treated with CPAP, residual excessive daytime sleepiness (REDS) persists. The prevalence, associations, and outcomes associated with REDS remain poorly understood. METHODS: Multicenter, prospective, observational cohort study including 1000 patients. Participants will undergo a sleep study for the diagnosis of obstructive sleep apnea (OSA), 24-h ambulatory blood pressure monitoring, clinical assessment, quality-of-life questionnaires, Epworth Sleepiness Scale, and collection of biochemical variables and biological samples. Patients with OSA will receive standard care, and those prescribed continuous positive airway pressure (CPAP) will be monitored for treatment adherence. OSA patients will be assessed at baseline and at 6, 12, and 24 months. DISSCUSION: We aim to establish a prospective observational cohort of patients with obstructive sleep apnea (OSA) treated with CPAP, with and without REDS. The HYPNOSA project will create the largest available registry of patients with OSA and REDS using real-world data, providing accurate prevalence estimates and long-term outcomes. Biological samples will be analyzed to assess the role of specific biomarkers. TRIAL REGISTRATION: Registered at ClinicalTrials.gov. Identifer: NCT06514482.

Adult

Antiadalimumab Antibodies in Patients With Inflammatory Ocular Diseases: Incidence and Clinical Outcomes.

PURPOSE: To determine the incidence, effect on adalimumab drug levels, and clinical consequences of antiadalimumab antibody formation, and to assess potential risk factors. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: One hundred twenty-eight patients treated with adalimumab who underwent antiadalimumab antibody monitoring. METHODS: Beginning October 2023, regularly scheduled antiadalimumab antibody and adalimumab level testing was begun. Using staggered entry analysis, anchored observation to treatment initiation, incidence was calculated. Time-updated models evaluated risk factors for antiadalimumab antibody formation. MAIN OUTCOME: Incidence of antiadalimumab antibodies. RESULTS: Antiadalimumab antibodies developed in 37 of 128 patients for a rate of 0.077 per person-year (PY) (95% confidence interval [CI] 0.055/PY, 0.104/PY). Median serum adalimumab concentrations were significantly lower in antiadalimumab antibody-positive blood samples (2.6 &#xb5;g/mL; interquartile range 0.8, 7.0) than in antibody-negative samples (10.2 &#xb5;g/mL; interquartile range 6.9, 15.1), P < .00001. In time-updated analyses, there was a suggestion that concomitant immunosuppression was associated with a reduced risk of antiadalimumab antibodies (odds ratio [OR] 0.64; 95% CI 0.37, 1.10; P = .10) and weekly adalimumab dosing was associated with a reduced risk (OR 0.62; 95% CI 0.42, 0.91; P = .01). Antiadalimumab antibodies were associated with active ocular inflammation (OR 3.68; 95% CI 1.99, 6.82; P < .00001). CONCLUSIONS: Antiadalimumab antibodies occur commonly among patients treated with long-term adalimumab, with a cumulative incidence of nearly 50% by 8 years of therapy. Antibody formation was associated with lower serum adalimumab levels and active ocular inflammation.

Humans