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PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗
PubMed2026

Disentangling oscillatory and aperiodic neural activity in autism: A spectral parameterization analysis of neurofeedback intervention.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by atypical neural oscillations and heterogeneous alterations in excitation/inhibition (E/I) balance, the directionality of which varies across individuals, neural circuits, and developmental stages. While Alpha-band neurofeedback (NFB) is a promising intervention, its underlying neurophysiological mechanisms remain unclear, partly due to the conflation of periodic and aperiodic signals in traditional EEG analysis. METHODS: This randomized controlled trial recruited 40 children with ASD, assigned to either an experimental group (Alpha-training NFB) or a no-feedback group. Resting-state EEG and behavioral assessments (SRS, ABC) were collected pre- and post-intervention. We employed spectral parameterization to decompose neural activity into aperiodic (1/f slope, offset) and periodic (periodic alpha power, center frequency) components. RESULTS: NFB training yielded significant behavioral improvements in social cognition and relating skills. Physiologically, the experimental group exhibited a significant steepening of the aperiodic slope (increased exponent), reflecting a reduction in neural noise and potential optimization of inhibitory modulation. Furthermore, we observed enhanced periodic alpha power and an acceleration of the alpha center frequency (ACF), indicative of improved neural efficiency and maturation. These physiological shifts in frontal and occipital regions were significantly correlated with improvements in behavioral scores. CONCLUSION: Alpha-training NFB was associated with improvements in caregiver-rated behavioral scores and modulated spectral features of resting-state EEG in children with ASD. These findings validate the utility of spectral parameterization markers in evaluating neuromodulatory interventions.

Humans↗
PubMed2026

The co-existence of Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome: A systematic review of the literature.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Humans↗
PubMed2026

Construction of circRNA-miRNA-mRNA regulatory networks in the intestine of turbot (Scophthalmus maximus) following Vibrio anguillarum infection.

Circular RNAs (circRNAs) play pivotal roles in post-transcriptional regulation by acting as molecular sponges for microRNAs (miRNAs) within the competitive endogenous RNA (ceRNA) network. However, the regulatory mechanisms in teleost immune responses remain poorly understood. In this study, circRNA-miRNA-mRNA networks were investigated in turbot (Scophthalmus maximus) following Vibrio anguillarum infection to elucidate host-pathogen interactions. Through high-throughput sequencing of intestinal tissues, a total of 50 differentially expressed circRNAs (DE-circRNAs) (18 at 2 hpi, 16 at 12 hpi, 16 at 48 hpi), 212 DE-miRNAs (11 at 2 hpi, 70 at 12 hpi, 15 at 48 hpi), and 1774 DE-mRNAs were identified. Functional enrichment analyses (GO/KEGG) revealed significant associations with immune pathways, including the MAPK signaling pathway and gap junction. An integrated circRNA-miRNA-mRNA regulatory network was constructed, highlighting key interactions including novel_circ_0002573/DE-miR-27a-3p/FGB and novel_circ_0002423/novel_347/GNE, which may regulate inflammatory and antibacterial responses. The expression patterns of selected circRNAs, miRNAs and mRNAs were validated using qRT-PCR, confirming the reliability of the sequencing results. Importantly, fibrinogen beta chain (FGB) and CXCR4/CXCL12 signaling were identified as critical immune modulators. These findings provide insights of the ceRNA regulatory networks involved in teleost intestinal immunity and provide potential molecular targets for selective breeding of disease resistance in this species.

Animals↗
PubMed2026

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals↗
PubMed2026

Maternal transfer of nonylphenol drives oxidative, immune, and epigenetic dysregulation in zebrafish offspring.

Nonylphenol (NP), a widespread surfactant and endocrine-disrupting pollutant, poses significant ecological and public health risks globally; however, its transgenerational effects remain poorly understood. Using zebrafish (Danio rerio), we compared chronic maternal NP exposure (50 and 100 µg/L, 28 days) with acute embryonic exposure (0.22 µmol/L) during 0-3 days post-fertilization (dpf) to delineate mechanistic differences in toxicity. Maternal NP exposure produced severe developmental defects in offspring, including edema, axial curvature, impaired swim bladder inflation, reduced growth, cardiac dysfunction, and decreased viability. These phenotypes were accompanied by systemic molecular disruptions including oxidative stress, altered estrogen receptor (ER) expression, dysregulated mitogen-activated protein kinase (MAPK) signaling, and suppressed innate immune response characterized by attenuated neutrophil/macrophage density, reduced CD68 and complement protein C3 expression, diminished nitrite load, and downregulation of pro-inflammatory mediators at both transcript and protein levels. Maternal exposure further induced apoptosis and persistent epigenetic reprogramming (alterations in DNA methylation and histone-modifying enzymes), hallmarks of transgenerational toxicity. In contrast, direct embryonic NP exposure elicited morphological abnormalities without significant lethality, accompanied by induction of pro-inflammatory cytokines, nitric oxide (NO) synthesis, and MAPK activation, reflecting an augmented inflammatory response. These mechanistic contrasts reveal that maternal NP exposure is a potent driver of systemic, heritable molecular reprogramming, whereas embryonic exposure triggers acute inflammatory pathways. Together, our findings underscore the global relevance of NP as a transgenerational toxicant, advocating for its urgent inclusion in ecotoxicological risk assessments and regulatory frameworks.

Animals↗
PubMed2026

Male accessory gland proteins in Grapholita molesta: Identification and reproductive functional validation of four accessory gland-specific lipases.

Accessory gland proteins (Acps), synthesized in the male accessory glands (AGs), are transferred to females via spermatophores during mating and elicit diverse post-mating physiological and behavioral responses. However, Acps have not been comprehensively characterized in Grapholita molesta, a cosmopolitan orchard pest. Here, using data-independent acquisition mass spectrometry, we describe an integrated proteomic approach combining comparative AG analyses (virgin vs. newly mated) with spermatophore profiling to identify Acps in G. molesta. According to the established screening criteria, we identified 83 confirmed Acps, which were classified into nine categories. Tissue-specific expression patterns of 20 randomly selected Acp genes were evaluated, revealing that these genes were specifically or highly expressed in male AGs. Among the 83 confirmed Acps, four Acps harbored the PLN02872 superfamily domain and were classified into the canonical lipase family. Notably, their transcripts were all highly expressed in the AGs during the pre-maturation stage. These four Acps were selected for preliminary validation of their male reproductive functions. RNAi-mediated knockdown of three out of four lipase genes in G. molesta males significantly decreased the fertility of mated females, with phenotypes including a significant reduction in egg production and egg hatching rate. This study provides a comprehensive catalog of high-confidence Acps, lays a foundation for subsequent in-depth functional characterization of these reproductive proteins, and offers promising molecular targets for the development of novel genetic regulation-based integrated pest management strategies.

Animals↗
PubMed2026

A clinical study on the efficacy of rectal administration of Tongfu Qinghua decoction combined with external application of Ruyi Jinhuang powder in treating acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdominal disease with high mortality in moderate and severe cases. Integrated Chinese and Western medicine therapy has promising clinical application prospects. OBJECTIVES: This study investigated the efficacy and safety of Tongfu Qinghua decoction enema combined with Ruyi Jinhuang powder external application for AP and its therapeutic effects across different age groups. METHODS: A total of 100 AP patients from October 2023 to August 2025 were randomly divided into observation and control groups (50 cases each). The control group received conventional Western medicine and the observation group received additional combined Chinese medicine therapy. Outcomes including hospital stay, symptom relief, inflammatory and pancreatic injury markers, clinical efficacy and adverse reactions were compared, with subgroup analysis of patients aged 18-40, 41-60 and 61-75 years. RESULTS: The observation group had significantly shorter hospital stay, faster symptom relief and gastrointestinal recovery (P<0.05). Post-treatment inflammatory and pancreatic markers improved significantly and the total effective rate was higher (P<0.05), with no significant difference in adverse reactions (P>0.05). Benefits were consistent across all age subgroups, with younger patients recovering faster and elderly patients still achieving significant improvement. CONCLUSION: This combined therapy is effective and safe for AP patients aged 18-75 years, significantly improving clinical outcomes and worthy of clinical promotion.

Humans↗
PubMed2026

The Incidence of Suicide Following Metabolic and Bariatric Surgery: A Prognosis Systematic Review and Meta-Analysis of Longitudinal Studies.

BACKGROUND: Metabolic and bariatric surgery (MBS) effectively manages severe obesity but may lead to psychological complications such as completed suicides and suicide attempts. This review aimed to analyze suicide and self-harm incidence post-MBS. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library databases on August 16, 2022, for longitudinal studies with incidence data on suicide following MBS. We performed a single proportion meta-analysis on the incidence of outcomes and assessed the certainty of evidence using the GRADE approach. The review was registered with PROSPERO (CRD42022352137). RESULTS: Eighty-four studies were included. The meta-analysis showed an incidence of 230.64 suicides per 100,000 participants (95% CI: 167.51 to 317.49) in pooled individual-level data and an incidence of 43.02 suicides per 100,000 person-years (95% CI: 32.49 to 56.97) in pooled person-year data. Evidence was low certainty or very low certainty. CONCLUSIONS: The average suicide incidence (231 per 100,000 people) in people with obesity who underwent MBS significantly exceeded the 2019 WHO global estimate for the general population (nine per 100,000 people). These findings underscore the need to incorporate structured psychological screening and follow-up into the perioperative management process of MBS, as patient mental health may play a pivotal role in postoperative adherence and long-term outcomes.

Humans↗
PubMed2026

Assessment of Surgical Salvage Outcomes for Exposed Cranial Neuromodulating Devices.

OBJECTIVES: Implanted neuromodulating devices (NMDs) such as cochlear implants (CIs) and deep brain stimulators (DBSs) are commonly used in modern medicine. Rarely, complications arise post-operatively, including hardware exposure. Traditional teaching suggests that these devices require removal if exposed; however, surgical salvage is a high risk, high reward alternative. We review our single institution experience managing NMD exposure with surgical salvage. METHODS: Retrospective chart review was performed on individuals who had a NMD implanted and underwent an attempt at surgical salvage for exposure during the study period (January 01, 2021 through December 31, 2023). Study outcome success was defined as maintaining a functional NMD 1&#x2009;year after salvage was attempted. Surgical techniques associated with successful salvage were compared. RESULTS: Nine of 729 patients (1.2%) implanted with NMDs experienced hardware exposure during this 2-year study period. Nine subjects were referred for NMD salvage; however, only 6 of 9 subjects (66.7%, CI&#x2009;=&#x2009;3; DBS&#x2009;=&#x2009;3) underwent NMD salvage attempts. Four of the subjects had successful salvage demonstrated successful salvage with a functioning NMD and without wound healing concerns 1&#x2009;year after their salvage procedure. CONCLUSIONS: Classic teaching states that exposed NMDs require explantation. However, this approach necessarily imposes time without benefit from the NMD between explantation and reimplantation. Our experience demonstrates that surgical salvage can be a successful alternative for the majority (66.7%) of individuals.

Humans↗
PubMed2026

Diagnostic criteria and severity assessment for syndesmosis injury using magnetic resonance imaging: A systematic review.

High ankle sprains involving syndesmosis injury present challenges in both diagnosis and severity assessment. Magnetic resonance imaging is widely regarded as the preferred modality for evaluating syndesmosis injury and related structural damage. This systematic review primarily examined the diagnostic utility of magnetic resonance imaging. Secondarily, it explores grading and prognostics of syndesmosis injuries with magnetic resonance imaging and identified possible imaging parameters predictive of injury severity. A comprehensive search of MEDLINE, Embase, CINAHL Complete, and Scopus was performed through February 12, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Peer-reviewed human studies in English that used magnetic resonance imaging to assess syndesmosis injury were included. Excluded were review articles, case reports, abstract-only studies, and biomechanical or cadaveric investigations. Twenty-seven studies comprising 1931 ankles met inclusion criteria. Magnetic resonance imaging demonstrated high diagnostic accuracy for complete tears of the anterior and posterior inferior tibiofibular ligaments. Ancillary signs such as the ring-of-fire edema pattern, distal tibiofibular joint effusion, and widening of the distal joint space exhibited high specificity with variable sensitivity and may assist in grading injury severity. Magnetic resonance imaging in chronic syndesmosis injury primarily detects fibrotic scarring and post-injury changes. Evidence gaps remain regarding the parameters that best determine injury severity and indicate early surgical intervention in competitive athletes. Consolidating multiple magnetic resonance imaging findings into standardized diagnostic criteria may improve reliability and clinical decision-making.

Humans↗
PubMed2026

Rhinoplasty Difficulty Scale: Development and Psychometric Analysis of a Surgeon's Assessment of Rhinoplasty Technique and Nasal Deformity Correction.

BACKGROUND: Rhinoplasty surgeons lack a universal scale of the relative difficulty of rhinoplasty techniques and rhinoplasty deformities. OBJECTIVE: To compare the expert opinion of the difficulty of rhinoplasty techniques and rhinoplasty deformities among international rhinoplasty surgeons, as measured by a scale of difficulty. METHODS: A cross-sectional survey of rhinoplasty surgeons collected training levels, experience, case volume, and perceived expertise. Rhinoplasty techniques/deformities (n = 64) were rated from 1-10, representing the least to most technically demanding. Rasch analysis was used to examine the fit of the observed data to Rasch model requirements, assess rating scale functioning, and provide estimates of internal consistency. RESULTS: Respondents (n = 63) were in practice (<5 years, 14%; 5-10, 20%; 10-20, 20%; 20-30, 26%; >30, 20%), and rhinoplasty volume ranged from <25 (14%) to >100 cases/year (32%). Self-reported expertise was comfortably novice (32%), intermediate (10%), advanced (28%), and expert (30%). Otolaryngology (42%), facial plastic surgery (30%), and plastic surgery (28%) were represented. Rasch estimates of internal consistency reliability were excellent (0.96 for surgeons and 0.99 for items); the item difficulties were more heterogeneous (mean: 0, SD: 1.23) than the distribution of surgeons (mean: -0.09, SD: 0.58). Survey items were ordered by difficulty, ranging from least difficult (inferior turbinate reduction = 1.01) to most difficult (contracted nose repair post-infection = 8.24). CONCLUSION: The newly developed Rhinoplasty Difficulty Scale provides ratings of common rhinoplasty techniques and deformities with a high correlation among experts using this rating scale.

Humans↗
PubMed2026

Penalized Cumulative Probability Model for a Continuous Outcome Subject to Detection Limits.

Mixed-type outcome data occur when the outcome variable's distribution is a mixture of both continuous and discrete ordinal variables. Such mixed-type outcomes are common in biomedical, psychological, and the health sciences, particularly for variables having either a detection or quantitation limit. When interest lies in identifying a combination of genomic features associated with a mixed-type outcome, any method used would require a variable selection strategy for high-dimensional data. Unfortunately, few variable selection methods exist for modeling a mixed-type outcome when the covariate space is high dimensional. This study develops a high-dimensional penalized cumulative probability model (CPM), to allow for the identification of genomic features associated with mixed-type outcome of interest. We demonstrated how such model may be estimated using the iterative penalization procedure-the generalized monotone incremental forward stagewise (GMIFS) algorithm. The Model-X knockoffs procedure was combined with the estimation algorithm to control the false discovery rates (FDR) when performing variable selection. Through extensive simulation studies, our penalized CPM was shown to outperform alternative methods in terms of controlled variable selection performance by achieving high statistical power with the FDR being controlled at the target level. We demonstrate the utility of our method by applying it to predict estimated glomeruli filtration rate (eGFR) in kidney transplant recipients at 24&#x2009;months post-transplant using baseline gene expression data as predictors. Our CPM model identified five genes associated with this mixed-type outcome which have important links to renal disease, which may provide prognostic guidance for kidney transplantation recipients.

Models, Statistical↗
PubMed2026

ChIP-seq profiling identifies diapause-regulated H3K27me3 targets in the fat body of Culex pipiens.

Culex pipiens, a principal vector of significant arboviruses, survives winter through diapause, a hormonally controlled inactive phase that enhances endurance under severe cold circumstances. Recent data suggests that epigenetic processes, namely histone post-translational modifications (hPTMs), play a crucial role in regulating seasonal dormancy. Prior studies from our laboratory indicated a decrease in the methylation of Histone 3 (H3K27me3) in diapausing fat body tissue, associated with elevated expression of the histone demethylase UTX. Nonetheless, the precise genomic areas impacted by these chromatin alterations remained unidentified. We used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) to delineate the genome-wide distribution of H3K27me3 across fat body chromatin in diapausing (D) and non-diapausing (ND) female Cx. pipiens. Notably, the higher signal at transcription start sites (TSSs) reflects localized redistribution rather than a global decrease, as diapausing fat bodies retain less H3K27me3 overall but concentrate it at promoters. To investigate the functional significance of these chromatin alterations, we confirmed a number of target loci via ChIP-qPCR and assessed gene expression with qRT-PCR. We identified many critical genes that were markedly increased in diapausing mosquitoes, exhibiting an inverse relation to H3K27me3 enrichment. Our data demonstrates different H3K27me3 chromatin landscapes between diapausing and non-diapausing Cx. pipiens, corroborating a hypothesis of selective, locus-specific repression in the non-diapause state and its targeted removal during diapause to permit activation of dormancy-associated genes. These results suggest that chromatin remodeling is a core driver of the diapause switch.

Animals↗
PubMed2026

Age-related differences in semen quality in Holstein-Friesian bulls: a paired within-bull comparison of early and mature reproductive stages.

Genomic selection has changed dairy cattle breeding by increasing the use of young bulls for artificial insemination and shortening the reproductive lifespan of sires. Under these conditions, semen quality at the beginning of commercial use has become an important practical issue. Semen samples from 39 fertile Holstein-Friesian bulls used for commercial AI were collected between 2013 and 2016, during the introduction of genomic selection in Poland. This paired within-bull study compared semen collected from the same bulls at an early reproductive stage (13-20 months; young bulls, YB) and at full maturity (5-6 years; mature bulls, MB). The evaluation included conventional ejaculate traits, CASA-derived motility and kinematic descriptors, mtDNA copy number, and mitochondrial content per sperm cell. Importantly, all ejaculates met the quality requirements for commercial insemination. Ejaculate volume, sperm concentration, mitochondrial DNA copy number, and mitochondrial content did not differ significantly between age groups. The CASA-derived sperm movement profile, in contrast, differed with age. Semen from young bulls showed a higher proportion of progressively motile spermatozoa, whereas semen from mature bulls showed higher velocity-related parameters, including VSL, VCL, and STR. These findings indicate that bull age mainly affected sperm movement characteristics rather than semen output or mitochondrial content. Overall, the results support the use of young bulls in artificial insemination programs and show that age-related differences in semen quality are expressed mainly through changes in the post-thaw sperm motility and kinematic profile.

Animals↗
PubMed2026

Long-term mortality in pediatric sepsis: a systematic review and meta-analysis.

BACKGROUND: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software. RESULTS: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I2 = 98.2%, p&#x2009;<&#x2009;0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited. CONCLUSION: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Humans↗
PubMed2026

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n&#x2009;=&#x2009;38) or to the control group (n&#x2009;=&#x2009;37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four&#x2009;weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans↗
PubMed2026

Effect of Music on Pain, Anxiety, and Satisfaction During Intrauterine Device Application: A Randomized Clinical Trial.

This randomized controlled trial aimed to determine the effect of music played during intrauterine device (IUD) insertion on perceived pain, state anxiety, and satisfaction levels. The study was conducted with 70 women who applied to a maternal and child health and family planning center and were randomly assigned to the intervention and control groups using simple randomization. Data were collected using a Demographic Information Form, the State-Trait Anxiety Inventory (STAI-I), and the Visual Analog Scale (VAS), as well as Bluetooth speakers and the musical piece Evgeny Grinko-Valse. Participants in the intervention group listened to music before and during the IUD insertion procedure, whereas the control group received routine care only. Data were analyzed using SPSS version 26 with appropriate descriptive and inferential statistical methods. Women in the music group had significantly lower perceived pain (p&#x2009;<&#x2009;0.001) and state anxiety levels during the procedure (p&#x2009;=&#x2009;0.022), and significantly higher satisfaction levels compared with the control group (p&#x2009;<&#x2009;0.001). In addition, post-procedure state anxiety levels were positively correlated with pain intensity experienced during and after the procedure (r&#x2009;=&#x2009;0.542 and r&#x2009;=&#x2009;0.496, respectively; p&#x2009;<&#x2009;0.001), and negatively correlated with procedural satisfaction (r&#x2009;=&#x2009;-0.652; p&#x2009;<&#x2009;0.001). These findings suggest that listening to music during IUD insertion may help reduce pain and anxiety while potentially enhancing patient satisfaction. Trial Registration: NCT06215183.

Humans↗