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Comparative effectiveness and safety of pharmacological interventions for sleep outcomes in chronic non-cancer pain: a systematic review and network meta-analysis.

Sleep disturbances are highly prevalent among individuals with chronic non-cancer pain and are associated with worse pain severity and poorer prognosis. The comparative trade-offs between the effectiveness and safety of available pharmacotherapies for sleep outcomes in this population remain poorly defined. Ninety-eight RCTs involving 28,920 participants (mean age 53.2 years, 71.2% female) were included. Moderate-certainty evidence demonstrated that melatonin significantly improved sleep quality compared with placebo (standardized mean difference [SMD] = -0.60, 95%CI: -0.98, -0.22). Ten agents (e.g., amitriptyline, oxycodone, gabapentin, pregabalin, duloxetine) also showed statistically significant improvements in subjective sleep quality (SMD = -0.24 to -1.07), but most effects were supported by low-certainty evidence and were accompanied by an increased risk of adverse events (odds ratio [OR] = 1.90 to 37.00). Conversely, melatonin was not associated with an increased risk (OR = 0.88, 95%CI: 0.19, 3.94). Our findings indicate that melatonin shows promise as a safe, adjunctive option for improving sleep quality in this population, but larger, condition-specific trials are warranted to confirm these effects. Other pharmacological agents are limited by lower-certainty and unfavorable safety profiles. These results should be interpreted cautiously given limited direct comparisons, heterogeneous chronic pain populations, the high proportion of trials at high risk of bias, and the predominance of subjective sleep outcomes.

Humans

Glymphatic dysfunction mediates inflammation-driven vascular burden and cognitive decline in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is increasingly recognized as a disorder involving microvascular dysfunction, impaired perivascular clearance, and inflammatory processes. However, how systemic inflammatory burden, neurovascular coupling (NVC), glymphatic MRI markers, vascular lesion burden, and cognition are interrelated remains unclear. MATERIALS AND METHODS: In this prospective study, 155 patients with CSVD and 70 healthy controls (HCs) underwent multimodal MRI. NVC was quantified using the cerebral blood flow/fractional amplitude of low-frequency fluctuations ratio. Glymphatic function was assessed via the diffusion tensor image analysis along the perivascular space (ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) fractions. Structural equation modeling (SEM) was employed to evaluate the direct and indirect effects of inflammatory markers on vascular burden and cognitive performance. RESULTS: Patients with CSVD exhibited significantly diminished NVC (specifically in the right median cingulate and left frontal gyri) and impaired glymphatic function (lower ALPS-index; higher CPV and PVS fractions) compared to HCs. SEM revealed that inflammatory biomarkers exerted both a direct effect on vascular burden and a substantial indirect effect (accounting for 66.3% of the total effect) mediated through two pathways: a single-mediation path via glymphatic function (42.8%) and a serial-mediation path via NVC and glymphatic function (23.5%). Increased vascular burden was significantly associated with poorer cognitive performance. CONCLUSION: Inflammation drives CSVD progression and cognitive decline primarily through the disruption of NVC and glymphatic clearance mechanisms. These findings highlight glymphatic dysfunction as a critical mediator of inflammation-related structural brain damage.

Humans

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female

Transcriptomic and Metabolomic Profiling Identifies a Core Gene-Metabolite Axis Driving African Swine Fever Virus Replication in the Soft Tick Ornithodoros lahorensis.

African swine fever virus (ASFV) causes an incurable swine disease with nearly 100% mortality, posing a catastrophic threat to global pig production. The soft tick Ornithodoros lahorensis acts as a critical biological vector that sustains persistent ASFV replication and mediates long-distance viral transmission, yet the molecular mechanisms governing ASFV-tick interplay remain poorly understood. Here, we integrated transcriptomics and metabolomics to systematically dissect molecular changes in O.&#xa0;lahorensis across three infection stages: Uninfected control, early infection (7&#x2009;days post-infection, dpi), and late persistent infection (21 dpi). Multi-omics integration revealed that ASFV extensively remodels tick host metabolism, predominantly activating purine/pyrimidine metabolism, lipid biosynthesis, and energy metabolism. We further characterized a conserved regulatory module consisting of 12 core genes and 8 signature metabolites that collectively support ASFV genome replication and virion assembly. Three hub metabolic genes (TK1, ATP5F1B, and IMPDH) were selected for functional validation via siRNA silencing in ticks; individual gene silencing suppressed ASFV loads by 89.2%, 91.5%, and 87.8%, respectively (p&#x2009;<&#x2009;0.001***). This work represents the first comprehensive multi-omics investigation of ASFV infection in O. lahorensis. We identified tick-specific molecular targets to block vector-mediated ASFV spread and established a standardized multi-omics analytical pipeline for tick-virus interaction research. Our findings elucidate the mechanistic basis of long-term ASFV persistence in soft ticks and deliver novel actionable clues for developing vector-targeted ASF intervention strategies.

Animals

Dynamics of soil fungal communities restored with biochar from a quarry site.

Quarrying activities have intensified due to population expansion, leading to landscape degradation and ecological destruction. Quarry restoration is usually mandatory in Hong Kong, China. Although biochar is used for sustainable soil amendment, its effectiveness in restoring quarry soil with poor properties has rarely been investigated. A 24-month field study was conducted to evaluate the ecological feasibility of restoring a quarry site by using native species (that is, Castanopsis fissa and Cyclobalanopsis edithiae) and biochar amendment. The results revealed that after 24 months, the application of biochar increased the organic carbon, phosphorus and potassium of the vegetated soil by at least 120 %, 31 % and 12 %, respectively, due to higher cation exchange capacity and better plant growth. The relative abundance of Ascomycota and Basidiomycota increased by 24 % and 47 % with biochar application when C. fissa was planted, which was likely associated with the improved nutrient cycling and soil fertility. Even though adding biochar to bare soil was found to increase the complexity of fungal co-occurrence networks, biochar application only increased fungal diversity in vegetated quarry soil but usually reduced its fungal richness. Moreover, fungal co-occurrence networks in vegetated soil became less complex, suggesting that biochar potentially helped plants to assemble specific, beneficial fungal communities. This effect is most pronounced in the soil planted with C. edithiae, where the structure of fungal communities after 24 months was significantly different from that at other restoration times. This study identifies key fungal phyla enhanced by biochar in quarry soil and provides an effective strategy for facilitating the restoration and management of degraded lands, especially quarry sites.

Charcoal

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145&#xa0;particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI&#xa0;=&#xa0;10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals

Ultrasound protocols used to detect vascular gas emboli in divers: a systematic review.

INTRODUCTION: Venous gas emboli (VGE) detected via ultrasound can be used as a surrogate marker for decompression stress. While Doppler ultrasound is the historical gold standard, two-dimensional (2D) ultrasonography offers advantages for on-site monitoring, including a wider field of view and reduced dependence on noise-free environments. This systematic review evaluates 2D ultrasonography protocols used in decompression research since the 2015 International Meeting on Ultrasound for Diving Research, identifying methodological similarities, differences, and adherence to consensus recommendations. METHODS: A search of PubMed and Scopus identified studies using 2D ultrasound to detect VGE in divers. Inclusion criteria were: (1) use of 2D ultrasound, (2) detection of VGE or monitoring of decompression stress, (3) inclusion of a diver cohort, and (4) publication after 2015. Data extraction focused on VGE scoring systems, ultrasound hardware, measurement protocols, and operator experience. Risk of bias was assessed using ROBINS-I-V2, and compliance with the 2015 consensus recommendations was evaluated. RESULTS: Twenty studies were included. The Eftedal-Brubakk scale was most commonly used (n = 15), with cardiac ultrasound as the primary imaging modality; one study assessed a peripheral vessel. Common shortcomings included post-dive measurements lasting less than two hours, underreporting of operator experience and hardware specifications, limited individual-level data, and inappropriate use of parametric statistics for ordinal bubble grade data. No study fully complied with all consensus recommendations. CONCLUSIONS: This review demonstrates that, although two-dimensional ultrasound is widely used for post-dive VGE assessment, methodological heterogeneity with multiple shortcomings remain. Furthermore, nearly all studies restricted imaging to the heart, thus leaving peripheral vessel assessment largely unexplored.

Embolism, Air

An introductory practical guide to secondary data analysis in pediatric urology.

INTRODUCTION: Secondary data analysis (SDA) has become an increasingly important approach in pediatric urology, enabling the study of long-term outcomes, care variation, and disparities in populations with chronic or congenital urologic conditions. With the growing availability of large datasets, a structured approach to designing and conducting SDA studies is increasingly relevant. OBJECTIVES: To provide an introductory, practical guide to SDA in pediatric urology by (1) summarizing commonly used data sources with representative studies, (2) outlining a stepwise approach to designing and executing SDA studies, and (3) highlighting key methodological considerations, limitations, and opportunities for future work. STUDY DESIGN: Narrative review of existing literature and commonly used datasets relevant to pediatric urology, including administrative claims, hospital encounter databases, clinical registries, electronic health record networks, and population-based surveys. RESULTS: Data sources differ in scope, clinical granularity, longitudinal follow-up, and representativeness, and each is suited to specific research questions. We present a practical workflow for SDA, including dataset selection, cohort definition, and analytic planning. Linkage across datasets can provide a more comprehensive view of care patterns and outcomes, although feasibility is influenced by legal, technical, and data-quality constraints. DISCUSSION: SDA enables population-level analyses and the study of rare conditions that are challenging to evaluate through single-center or prospective designs. However, careful cohort definition, feasibility assessment, and awareness of data limitations are essential to ensure validity and interpretability. CONCLUSION: SDA provides a scalable, cost-efficient framework for generating meaningful evidence in pediatric urology. Continued efforts to harmonize data elements, improve linkage infrastructure, and support cross-institution collaboration will enhance the quality and impact of future research. This article provides a practical framework and examples to support the design and execution of SDA studies.

Humans

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans

The future of pediatric vesicoureteral reflux management.

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition in pediatric urology, yet important uncertainties persist regarding risk stratification, imaging strategies, and prevention of long-term renal damage. Emerging technologies may help address these challenges. This review provides a forward-looking overview of recent advances in artificial intelligence (AI) and immunomodulation that may influence future management of pediatric VUR. METHODS: A forward-looking literature review was performed using the PubMed database (January 2000-March 2025), focusing on studies addressing AI, immunomodulation, or vaccination in the context of VUR and urinary tract infections. Criteria of inclusion were the relevance to pediatric VUR, the novelty of the proposed concept, the potential clinical implications and, for the AI literature, the existence of a clinical evaluation of the algorithm on a dataset from patients. KEY FINDINGS AND LIMITATIONS: AI-based models show promising performance in supporting clinical decision-making, including prediction of the need for voiding cystourethrography, automated grading of VUR, estimation of recurrent urinary tract infection risk and prediction of chemoprophylaxis. These tools may facilitate more individualized diagnostic and therapeutic strategies, although current evidence is largely retrospective and requires prospective validation. Immunization and immunomodulatory approaches aim to reduce infection burden and modulate inflammatory pathways associated with renal scarring. While early experimental and adult clinical data are encouraging, pediatric-specific evidence remains limited, and clinical applicability in children with VUR is not yet established. CONCLUSION: Artificial intelligence and immunologically targeted strategies represent complementary, emerging approaches that may contribute to more personalized management of pediatric VUR. At present, both should be regarded as exploratory tools whose clinical impact will depend on further validation and appropriately designed pediatric studies.

Humans

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals

Can host genetics transform the sustainable control of tropical theileriosis? Insights from the Tick-Theileria interface.

Tropical theileriosis, caused by the tick-transmitted apicomplexan parasite Theileria annulata, remains a major constraint on cattle production across North Africa, the Mediterranean basin, the Middle East and South Asia. Current control depends on acaricides, the theilericidal drug buparvaquone and live attenuated schizont vaccines, but acaricide resistance, buparvaquone-resistance mutations and the logistical demands of vaccination are eroding the sustainability of these tools. Host genetics offers a complementary and durable alternative. Indigenous Bos indicus breeds are consistently more resistant to ticks and tolerate T. annulata infection better than exotic Bos taurus cattle, and this advantage has a measurable heritable component. Unlike previous reviews, which treat tick resistance, T. annulata immunobiology and livestock genomic selection as separate subjects, we integrate all three and assess host genetics specifically against the failure modes of current control. We review the tick, parasite and host interface, the evidence for natural resistance, and the genetic and immunological mechanisms involved, including signal-regulatory protein, bovine major histocompatibility complex class II and inflammatory pathway genes. We then assess whether genomic selection, multi-omics, machine learning and gene editing can translate these mechanisms into resistant cattle, and we weigh the biological, economic and infrastructural barriers to implementation. The evidence indicates that host genetics will not replace existing control but could reduce reliance on acaricides and chemotherapy. That contribution remains prospective rather than demonstrated: no resistance marker for T. annulata has yet been validated, prediction accuracies are moderate and transfer poorly between breeds, and no endemic production system has implemented selection for resistance.

Animals

Efficacy and safety of postoperative chewing gum for gastrointestinal recovery in children undergoing surgery: an updated systematic review and meta-analysis.

Chewing gum may stimulate gut motility through a "sham feeding" mechanism, but evidence in children is limited. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing chewing gum plus usual care versus usual care alone in patients younger than 18 years undergoing any surgery. We searched five databases through June 2025. Primary outcomes were the time to first flatus, time to first defecation, and postoperative length of stay (LOS). Certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Ten studies (n&#x2009;=&#x2009;649) were included: abdominal surgery (5), spinal fusion (3), and tonsillectomy (2). Chewing gum may result in little to no difference in the time to first flatus (MD&#x2009;-&#x2009;3.58&#xa0;h, 95% CI&#x2009;-&#x2009;8.08 to 0.91) or first defecation (MD&#x2009;-&#x2009;3.23&#xa0;h, 95% CI&#x2009;-&#x2009;6.63 to 0.18), both with low certainty. LOS evidence was very uncertain (MD&#x2009;-&#x2009;0.18 days, 95% CI&#x2009;-&#x2009;0.70 to 0.33). Subgroup analyses suggested shorter LOS after abdominal surgery (MD&#x2009;-&#x2009;0.60 days, 95% CI&#x2009;-&#x2009;1.99 to 0.79) but not after spinal fusion (MD 0.10 days, 95% CI&#x2009;-&#x2009;0.29 to 0.50; p for interaction&#x2009;=&#x2009;0.0362). The benefits of postoperative chewing gum in children remain uncertain, with potential surgery-specific differences in LOS warranting investigation.

Humans

Specialized pro-resolving mediators in obesity and overweight conditions: A systematic review of human and animal evidence on comparative differences and associations.

Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.

Animals

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals

The Role of Small Segmental Duplications in Generating Identical Isoforms Through Alternative Splicing Sites.

Alternative splicing plays a crucial role in expanding proteomic diversity but can also generate identical isoforms under certain conditions. While mutually exclusive splicing of tandem exons has occasionally been reported to produce identical isoforms, the extent to which other splicing events contribute to this phenomenon remains unclear. In this study, we demonstrate that alternative 5' and 3' splice site selection can also lead to the formation of identical isoforms, providing an additional type of splicing event for functional redundancy in transcriptomes. To address this, we analyzed reference genome annotations from 15 plant species, including Arabidopsis thaliana and wheat (Triticum aestivum), obtained from the RefSeq database. Identical isoforms were computationally defined as transcripts with distinct exon-intron structures but identical coding sequences. Our analysis reveals that the majority of alternative 5' and 3' fragments originate from small segmental duplications, suggesting that sequence repetition within gene regions facilitates the emergence of such splicing patterns. We also observed differences in the annotated 5' UTRs of some identical isoforms. However, since the alternative splicing sites themselves were not located within UTRs, these differences may reflect annotation uncertainty rather than genuine AS-derived variation. Given that UTR predictions in reference databases are not always precise, such observations should be interpreted cautiously. Expression analysis using an isoform-specific k-mer approach confirmed that identical isoforms can be differentially regulated. These findings suggest that, beyond expanding protein diversity, alternative splicing can also generate redundant isoforms that are differentially expressed at the RNA level, indicating potential regulatory roles. By elucidating the structural and regulatory factors contributing to the formation and retention of identical isoforms, our study provides new insights into the evolutionary and functional significance of alternative splicing in plants.

Alternative Splicing

Parents' Awareness of Their Adolescents' Sexual Behaviors and Experiences: A Concordance Analysis.

PURPOSE: Adolescence is a developmental period during which sexual exploration is normative. Parental awareness of adolescents' sexual behaviors can be protective during this stage; however, research suggests both parents and adolescents tend to avoid open conversations about these sensitive issues. This study aimed to examine concordance between parent proxy-reports and adolescent self-reports across three domains of adolescents' sexual behaviors and experiences. METHODS: Data were collected from a national sample of 522 parent-adolescent dyads (aged 15-17 years) from the AmeriSpeak panel (data collected May-September 2022). Prevalence-adjusted bias-adjusted kappa (PABAK) statistics were calculated to evaluate agreement. RESULTS: Findings revealed weak-to-moderate concordance regarding adolescents sending and receiving sexual photos (PABAKs = 0.54-0.79), whereas stronger concordance was observed for experiences related to nonconsensual sharing of sexual photos (PABAKs = 0.92-0.94), with high agreement largely driven by low reported prevalence of these experiences. Strong concordance regarding whether adolescents had ever had sex (PABAK = 0.80) was largely driven by both parents and adolescents reporting the adolescent had not had sex. Concordance regarding sexually transmitted infection and pregnancy prevention methods varied, ranging from weak to strong agreement across specific methods (or lack thereof; PABAKs = -0.07-0.79). DISCUSSION: Results highlight significant discrepancies in parents' knowledge about their adolescents' sexual behaviors and experiences. Interventions aimed at enhancing trust and open dialogue between parents and adolescents about sexuality-related topics, as well as ensuring adolescents have a variety of trusted sources to consult for sexual information, can help adolescents make informed sexual health decisions.

Humans

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans