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PubMed2026

Playing with Fire, Losing the Drive: Bidirectional Links Between Problematic Smartphone Use and Grit Dimensions.

This study examined bidirectional longitudinal associations between grit dimensions (consistency of interest [CI] and perseverance of effort [PE]) and problematic smartphone use (PSU) and tested cognitive flexibility as a mediating mechanism. A sample of 1,641 Chinese university students (55.2 percent female; Mage = 20.1 years) completed measures at two time points 6 months apart. A four-variable cross-lagged panel model revealed that CI and PSU negatively predicted each other over time, whereas PSU unidirectionally predicted decreased PE. Cognitive flexibility partially mediated the PSU-to-PE pathway (indirect effect = -0.004, 95 percent bootstrap CI [-0.010, -0.0001]). Competing models analysis confirmed this directionality: the forward mediation (PSU → cognitive flexibility → PE) was significant, whereas the reverse was not. These findings demonstrate that grit dimensions exhibit distinct longitudinal patterns with PSU and identify cognitive flexibility as a cognitive mechanism through which PSU specifically undermines effort persistence. Implications for dimensional approaches to grit and targeted interventions are discussed.

Humans↗

PubMed2026

Patient-reported outcome measures for depression or anxiety symptoms in patients with cardiovascular disease: A COSMIN systematic review.

BACKGROUND: Depression and anxiety are common in patients with cardiovascular disease (CVD), but the measurement quality of patient-reported outcome measures (PROMs) used in this population remains unclear. This review aimed to evaluate the methodological quality, measurement properties, and certainty of evidence for depression and anxiety PROMs in adults with CVD and to inform instrument selection. METHODS: Following COSMIN and PRISMA guidance, four databases were searched from inception to February 2026. Studies assessing measurement properties of PROMs in adults with CVD were included. Methodological quality was evaluated using the COSMIN Risk of Bias checklist, and certainty of evidence was graded using an adapted GRADE approach. RESULTS: Sixty-six studies assessing 38 PROMs were included, comprising 29 generic and 9 CVD-specific instruments. Six PROMs met COSMIN Category A criteria: Cardiac Depression Scale-Short Form, Patient Health Questionnaire-9, Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Generalized Anxiety Disorder-7, and Major Depression Inventory. Four instruments were classified as Category C because of insufficient structural validity. Content-validity evidence was largely indeterminate or of limited certainty. Only 24 studies used confirmatory factor analysis or Rasch analysis, and no study assessed measurement error or responsiveness. Cross-cultural validity evidence was scarce. CONCLUSIONS: Six PROMs met Category A criteria, but selection should remain purpose- and context-specific. Particular attention should be given to somatic symptom overlap and intended clinical use. Further validation should prioritize content validity, measurement invariance, responsiveness, measurement error, and clinimetric performance.

Humans↗

PubMed2026

A profile of firearm-related fatalities admitted to the Diepkloof Forensic Pathology Service Soweto medico-legal mortuary during the COVID-19 and post COVID-19 periods.

This retrospective descriptive study examined firearm-related fatalities during (April-December 2020; n = 241) and after (April-December 2023; n = 299) COVID-19 lockdowns using 540 cases from the Diepkloof Forensic Pathology Service, Soweto, South Africa. Data was obtained from autopsy reports, forensic records, police statements, and death scene documentation. Firearm violence affected young adult Black males (22-43 years), with only minor demographic shifts post-pandemic. The overall burden and core patterns of violence remained stable, with criminal activity - primarily robbery and interpersonal violence - persisting as the leading contexts, and homicide the dominant manner of death. Post-COVID-19 findings demonstrated contextual shifts, including increased incidents in public and social environments, reflecting greater mobility and resumption of social activity. A significant rise in mean blood alcohol concentration (0.09 g/100 mL vs 0.14 g/100 mL; p < 0.0001) suggests increased alcohol involvement following easing of restrictions. Unfortunately, persistent information gaps, noted particularly in circumstantial history, incident location, firearm type, highlighting the need for improved data provision and capture systems. While the epidemiology of firearm-related fatalities remained unchanged, the post-COVID-19 period was characterised by increased alcohol involvement, shifts toward public-space violence, and fewer gunshot wounds per victim, suggesting changes in situational and behavioural dynamics rather than underlying drivers of violence.

Humans↗

PubMed2026

Efficacy of a self-guided online resilience intervention for improving mental health among university students: A randomized controlled trial.

Epidemiological data indicates that university students are an at-risk population for the development of mental disorders. Online interventions have been proposed as promising tools for reducing barriers to treatment and establishing easily accessible health-care services promoting mental health and resilience. This study investigated the efficacy of a Learning Management System (LMS)-based self-guided online resilience intervention. 216 university students took part in a randomized controlled trial with an intervention and a waitlist control group and three measurement points (pre, post and follow-up). We conducted per-protocol (PP) and intention-to-treat (ITT) analyses with mental distress as primary outcome, and self-reported resilience and resilience factors as secondary outcomes. Further, attitudes towards online interventions, adherence, satisfaction and possible negative effects were explored. Satisfaction with the intervention was high and PP analyses (n = 150) revealed significant improvements in mental distress and self-compassion at post-test and acceptance at follow-up. No favourable effects were found for self-reported resilience and resilience factors. Adherence was low and ITT analyses revealed no significant effects. Overall, the study provides preliminary evidence for the LMS-based self-guided online intervention as a potentially valuable tool for university mental health services under optimal adherence conditions. Further research into determinants of adherence is needed to improve intervention reach.

Humans↗

PubMed2026

Viral replication through phase separation: Cytosolic and nuclear condensates.

Replication of many RNA and DNA viruses occurs within specialized intracellular hubs organized as membraneless biomolecular condensates (BCs) driven by liquid-liquid phase separation. As obligate intracellular parasites, viruses depend on the host cell machinery to complete their replication cycles and therefore actively remodel the intracellular environment to favor viral genome replication, transcription, and assembly. Cytosolic and nuclear phase-separated replication compartments (RC) provide concentrated and dynamic platforms that promote efficient interactions between viral genomes and viral or host proteins essential for infection. The formation of viral replication BCs is typically facilitated by viral proteins enriched in intrinsically disordered regions and low-complexity domains, which enable multivalent interactions with viral nucleic acids and cellular factors. These interactions are mediated by diverse biophysical forces, including hydrophobic and π interactions, hydrogen bonding, molecular crowding, and osmotic effects. Throughout infection, viral BCs remain highly dynamic, allowing continuous exchange of components and functional maturation of replication hubs. Their properties and activities are further regulated by post-translational modifications of viral and host proteins, such as phosphorylation, acetylation, and methylation. In this review, we summarize current evidence supporting liquid-liquid phase separation as a central organizing principle of viral RCs. We focus on representative RNA and DNA viruses that replicate in the cytosol or nucleus, highlighting virus-specific strategies, conserved mechanisms, and the consequences of BC formation for viral replication efficiency, host antiviral responses, and therapeutic intervention.

Phase Separation↗

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

Safety and efficacy of recombinant botulinum toxin type A (Eveotox®) in patients with post-stroke upper limb spasticity: Results from a Phase Ib/II clinical trial.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Humans↗

PubMed2025

Examining Behavioral Interventions for Infancy and Early Toddlerhood: A Systematic Review of Intervention Effects, Parameters, and Participants.

Rapid advancement is paving the way to identify children who would likely benefit from early intervention during the first years of life, prior to the onset of significant delays in development. With the widely acknowledged benefits of early intervention, key questions arise: Does behavioral intervention targeted to infancy and early toddlerhood improve developmental outcomes? What procedures might be used, and under what circumstances? Who do these interventions work for? The current review comprehensively examined the literature on behavioral interventions based in operant learning, focused on key developmental areas with children in the first two years of life. We located and synthesized 69 studies with unique participant cohorts that included 1735 children. The search revealed many studies focused on the first year of life, of which a large proportion investigated approaches to increase communication. We provide implications, limitations, and future directions on how behavioral interventions for infants and young toddlers can inform current practice and future intervention research this population.

Humans↗

PubMed2026

Applications and outcomes of virtual reality in inpatient psychiatry: A systematic review.

BACKGROUND: Virtual reality (VR) has been widely used in outpatient psychiatric services and has demonstrated benefits across several clinical diagnoses, but its use and effects in inpatient settings remain to be explored. This systematic review aimed to examine the use of VR during psychiatric hospitalization, including types of VR applications, barriers and facilitators of implementation, and effects on various outcomes. METHODS: The review was registered in PROSPERO (#CRD42023446524). Following PRISMA guidelines, databases (Ovid, SciVerse, Web of Science, Cochrane Library, ProQuest, and WorldCat) were searched from 1983 to 2025 using keywords related to VR and psychiatric disorders. Studies involving the use of VR with psychiatric inpatients (≥85%) were included. Descriptive statistics and narrative syntheses were used to summarize findings. Study quality was assessed with the Mixed Methods Appraisal Tool. RESULTS: After full-text screening, 37 studies (N = 1,004) met inclusion criteria. VR was used for both assessment and intervention, with cognitive-behavioral therapy/exposure (35%) and assessment (24%) being the most frequently used. VR use in inpatient units appeared feasible, acceptable, and safe for inpatients and clinicians, though findings remain preliminary. Several facilitators (e.g. adequate staff training and supervision) and common barriers (e.g. technical difficulties and limited resources) were identified. The most consistent improvements were observed in clinical symptoms (e.g. anxiety) compared with psychosocial, cognitive, and physiological outcomes. CONCLUSIONS: These findings suggest that inpatient settings represent a promising, yet understudied context for VR-based assessments and interventions. High-quality trials and systematic reporting of implementation are needed in future studies to inform research and clinical practice.

Humans↗

PubMed2026

Toileting dysfunction in SATB2-associated syndrome: results from a caregiver survey.

BACKGROUND: Toilet training and continence are major developmental milestones, but children with neurogenetic conditions often experience extreme difficulties, sometimes never achieving full continence. These challenges impose ongoing burden on caregivers, especially as children age and require toileting assistance outside the home. SATB2-associated syndrome (SAS) is a rare genetic disorder in which such functional issues have not been systematically studied. We sought to assess bladder and bowel function in individuals with SAS and compare symptoms burden to normative data. METHODS: Caregivers completed a survey that included the Vancouver Symptom Score (VSS) for Dysfunctional Elimination Syndrome. VSS scores were analyzed and compared to published norms. Additional data included toilet training milestones, continence status, urinary tract infections, and bowel treatment history. RESULTS: Of the 32 individuals with SAS represented in the caregiver-reported survey, over half (53%) were not toilet trained, and only 22% were fully trained for both day and night (mean age at toilet training 6.9 years). The SAS group (n = 32) had a median total VSS of 16.0 (range: 6-30), indicating clinically significant dysfunction, while control data (n = 49) reported a median of 5.0 (range: 0-12, p < 0.001), with the greatest differences observed in daytime wetting, nighttime wetting, wetting extent, and fecal soiling. CONCLUSIONS: Individuals with SAS experience markedly elevated elimination symptom burden. Findings support the need for early screening and intervention to promote continence and reduce caregiver strain. A clinical pathway is proposed for screening, evaluation, and management of elimination dysfunction in SAS.

Humans↗

PubMed2025

The Factors That Contribute to Dysfunctional Behavior in Active Military Personnel: An Umbrella Review.

Dysfunctional behavior in active military personnel is a complex and challenging issue for military forces worldwide. Effective management of this issue requires a comprehensive understanding of the factors that contribute to dysfunctional behavior in military populations. The current study presents an umbrella review that synthesized and analyzed the existing literature on contributory factors to dysfunctional behavior in active military personnel using a systems thinking-based framework. Eleven systematic reviews were identified as eligible for inclusion in the umbrella review. The synthesis identified 14 contributory factors to the following types of dysfunctional behavior: suicidal behavior, substance misuse, domestic violence perpetration, and destructive leadership. The analysis indicated that existing literature focuses on contributory factors relating to the military personnel themselves and not influences in the broader military system or wider society. Additionally, few studies have sought to understand how factors interact to create dysfunctional behavior. Future research would benefit from the use of systems thinking-based frameworks and methods to investigate the factors, across the broader military system and society, that contribute to dysfunctional behavior in active military personnel.

Humans↗

PubMed2026

Melatonin Levels in 89 Individuals With Smith Magenis Syndrome.

In patients with Smith-Magenis syndrome (SMS), an inverted circadian rhythm of melatonin (MT) contributes to the sleep disturbance. Standard treatment of sleep disturbance with MT often leads to extremely high daytime MT levels, resulting in even more sleep disorders. We therefore retrospectively evaluated the MT data of 89 SMS patients. Mean MT levels in participants on exogenous MT were significantly higher than in participants that did not use MT (p = < 0.0001). In 9 participants with very high MT levels, these dropped significantly after discontinuation of exogenous MT (p = 0.0037). In 12 participants, MT levels were significantly higher after MT therapy start compared to MT levels before MT start (p = 0.028). MT is catabolized principally by the CYP1A2 enzyme, with a half-life of about 40 min. CYP1A2 genotyping was performed in five participants with high MT levels during MT use. Although clinically suspected to be a poor CYP1A2 metabolizer, all five turned out to have haplotype CYP1A2*1F, which is associated with increased enzyme activity. This shows that genotyping of CYP1A2 is not suitable to estimate the level of CYP1A2 enzyme activity. When prescribing MT, it is strongly recommended to measure a MT level prior to treatment in order to determine the dose to be given. Checks of the MT level during treatment are necessary due to the frequent occurrence of poor CYP1A2 metabolism. Since CYP1A2 genotyping does not provide adequate information about the level of CYP1A2 enzyme activity, we propose a simple way to determine CYP1A2 phenotype.

Humans↗

PubMed2026

Noncombustible Nicotine or Tobacco Product Use After Smoking Cessation and Major Vision-Impairing Diseases: A Nationwide Cohort Study.

OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to noncombustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco. DESIGN: Retrospective cohort study. PARTICIPANTS: About 179 273 adults from the Korean National Health Insurance Service who smoked CC in 2011 to 2012 and reported cessation in 2018 to 2019, classified into complete quitters and NNTP switchers. METHODS: This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk. MAIN OUTCOME MEASURES: Adjusted SHRs for incident major vision-impairing eye diseases. RESULTS: Among 32 316 matched participants followed for a mean of 4.6 years, 6328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups. CONCLUSIONS: Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.

Humans↗

PubMed2026

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans↗

PubMed2026

Redefining the real problem in psychedelic trials: Why fighting the Lessebo matters more than blinding integrity.

Imperfect blinding is not specific to psychedelic trials. In randomized trials, treatment allocation is frequently correctly guessed, yet blinding integrity is rarely assessed outside of psychedelic research and is generally not considered a barrier in regulatory evaluation. The intense debate in psychedelics may reflect a broader double standard affecting mental health research, when uncertainties arising from imperfect blinding are confounded by those linked to patient-reported outcome measures. Indeed, people living with mental disorders are often viewed as unreliable reporters, despite well-documented limitations of clinician-rated scales and the absence of robust biological markers of symptomatic change. Importantly, it is the maintenance of reasonable doubt of treatment allocation that sustains internal validity and ethical feasibility of placebo-controlled designs, rather than perfect blinding. Concerns about expectancy bias in psychedelic trials are closely tied to blinding debates. When allocation is inferred, expectations may cluster in the arm perceived as active or in stereotyped experiences and influence outcomes differently in active and control arms, leading to a risk of lessebo, a negative placebo effect due to the negative expectation related to receiving a placebo. However, we argue that an underrecognized mechanism of lessebo is disappointment. This risk may reflect insufficient clinical management of disappointment rather than pre-treatment expectation alone. We therefore propose shifting the emphasis from preserving inevitably imperfect blinding towards mitigating disappointment in both arms. Establishing non-stereotyped expectations prior to treatment through structured psychoeducation, strengthened therapeutic alliance, and realistic preparation would help avoid lessebo effects. Such strategies would enhance ethical rigor, interpretability, and the clinical usefulness of psychedelic trials.

Humans↗

PubMed2026

The interplay between circadian misalignment or sleep disturbances and cognition and brain function in individuals with different degrees of insulin resistance - a systematic review.

Disruption of sleep increases the risk of type 2 diabetes and worsens cognitive outcomes, yet few studies have evaluated the interaction between insulin resistance and sleep parameters in relation to cognitive outcomes or the risk of dementia. This systematic review examines how circadian misalignment and sleep disturbances affect cognition and neuroimaging findings in individuals with varying degrees of insulin resistance. Across 27 studies, disrupted circadian rhythmicity and sleep disturbances were negatively associated with brain health, possibly through its effects on insulin sensitivity, whereas the impact of sleep duration and quality were inconclusive. Methodological heterogeneity, reliance on cross-sectional designs, and limited control for confounders restricted definitive conclusions and highlighted the need for longitudinal and interventional studies with objective measurements. Nonetheless, the findings support circadian rhythmicity as a potentially modifiable risk factor for preserving cognition in insulin-resistant populations. Future research should prioritise prospective and interventional studies and focus on biological markers rather than self-reported outcomes.

Humans↗

PubMed2026

Genetic Screening of Colombian Patients With Early-Onset Parkinson Disease.

BACKGROUND AND OBJECTIVES: Early-onset Parkinson disease (EOPD), defined as symptom onset before 50 years of age, accounts for approximately 10% of patients and is suggested to have a greater genetic component than typical late-onset forms of the disease. Recessive variants in PRKN, PINK1, and DJ-1, are the most common genetic cause of EOPD, however, most studies are in patients of white ancestry. This study aims to analyze genetic variants in PRKN, PINK1, and DJ-1 in Colombian patients to help address the gap in EOPD genetic research of South American populations. METHODS: We analyzed 43 unrelated patients with EOPD using Sanger sequencing for the PRKN, PINK1, and DJ-1 genes and employed multiplex ligation-dependent probe amplification to detect copy number variants. Additionally, long-read whole-genome sequencing was conducted on 3 unresolved patients with age at onset before 30 years of age (long-read sequencing [LRS] patient A-C). RESULTS: We identified known pathogenic single-nucleotide variants and copy number variants in the PRKN gene accounting for 2 patients' disease (4.6% of patients). We observed 2 pathogenic variants in PRKN (c.155delA; p.N52Mfs*29 and c.1083+1G>A) in patient 1, who reported an age at onset of 16 years. We further detected a homozygous duplication of PRKN exons 5-6 in an additional patient, age at onset of 18 years. DISCUSSION: Our study helps characterize genetic contributors to EOPD in Colombian patients, demonstrating genetic forms (PRKN, PINK1, and DJ-1) are rare. Our results highlight a need to include diverse populations in research to improve genetic understanding of disease.

Journal Article↗

PubMed2026

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

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

Animals↗