Tag: pubmed

J Mol Endocrinol. 2026 Mar 25:JME-25-0171. doi: 10.1530/JME-25-0171. Online ahead of print.

ABSTRACT

Physiologic mechanisms underlying metabolic and renal diseases interact and are highly comorbid, yet their genetic associations and underlying mechanisms have not been systematically elucidated. Using Genome-Wide Association Study (GWAS) summary statistics from UK Biobank, FinnGen, and CKDGen, we integrated and analyzed gout, serum urate, chronic kidney disease, kidney stones, and metabolic syndrome. Using genomic structural equation modeling (GSEM), we created the first genetic linkage map for “Gout-Urate-Kidney-Metabolism” (GUKM) to explore shared genetic architecture. Post-GWAS analyses for GUKM-GSEM GWAS, including functional annotation, enrichment, fine-mapping, causal inference, and gsMap, identified key genetic loci, pathways, tissues/cell types, and potential drug targets. We identified 164 lead SNPs, including rs1260326 (chr2) and rs73607783 (chr8), with GSEA showing significant enrichment of GUKM-GSEM GWAS in cholesterol metabolism and lipid pathways (adjP < 0.05). Tissue and cell enrichment highlighted the liver, renal cortex, pancreas, proximal tubular epithelial cells, and hepatocytes (P < 0.05). Mendelian randomization indicated a potential causal role of GCKR (FDR < 0.05), which gsMap showed to be highly expressed in hepatocytes and liver tissue. The present study revealed the common genetic basis of metabolic and renal diseases and emphasized that lipid metabolism may be a key intermediary pathway connecting the “metabolic-renal axis.” The liver, renal cortex, and pancreas were the primary enriched tissues, and GCKR was identified as a core gene and potential drug target. Overall, this study provides an important reference for the genetic mechanisms, key mechanisms, and intervention targets of related diseases.

PMID:41926080 | DOI:10.1530/JME-25-0171

Spine Deform. 2026 Apr 2. doi: 10.1007/s43390-026-01354-6. Online ahead of print.

ABSTRACT

PURPOSE: Evaluate the utility of intraoperative traction (IOT) during posterior spinal fusion (PSF) in a matched cohort at a high-volume neuromuscular scoliosis (NMS) center.

METHODS: A nested case-control study was performed on a single-center retrospective database of NMS patients. Those diagnosed with cerebral palsy were pair-matched by age (± 1 year), preoperative curve magnitude (± 10°), preoperative traction curve magnitude (± 10°), and flexibility index (± 5%). Paired t tests or Wilcoxon signed-rank tests were used to analyze continuous variables between groups. Fisher’s Exact tests were used to compare categorical variables by group.

RESULTS: Thirty-one unique case-control matches were identified (n = 62). IOT and non-IOT groups were similar in terms of EBL 855 (IQR 500-1200) vs. 800 (IQR 650-1350) cc (p = 0.60), length of ICU stay 1.7 (IQR 1.0-2.7) vs. 2.3 (IQR 1.7-3.1) days (p = 0.14), BMI 18.0 (IQR 14-20) vs. 15.5 (IQR 14-18) (p = 0.10), sex distribution 54.8% vs. 51.6% (p > 0.99), and changes in neuromonitoring signals 4/31 (13%) vs. 3/31 (10%) (p > 0.99). Complication rate was 22.6% (7/31) for IOT and 25.8% (8/31) for non-IOT (p > 0.999). There were no statistical differences in surgical time 414 ± 131 vs. 397 ± 133 min (p = 0.64) or anesthesia time 551 ± 136 vs. 529 ± 135 min (p = 0.56). Both groups had similar postoperative curve magnitude IOT = 37° vs. non-IOT = 42° (p = 0.28) and percent curve correction IOT = 60% vs. non-IOT = 56% (p = 0.30). Percent correction of pelvic obliquity was also similar 78% (IQR 67-90) vs. 68% (IQR 60-91) (p = 0.18) between groups.

CONCLUSION: There was no difference in postoperative curve correction or pelvic obliquity between those treated with IOT versus those without during PSF.

LEVEL OF EVIDENCE: III.

PMID:41926074 | DOI:10.1007/s43390-026-01354-6

Can J Public Health. 2026 Apr 2. doi: 10.17269/s41997-026-01190-1. Online ahead of print.

ABSTRACT

BACKGROUND: While the literature indicates that corporal punishment, and specifically spanking, is associated with several poor outcomes, little is known about the prevalence of spanking and attitudinal beliefs about spanking in Canada. The overall aims of the study were to (1) compute the prevalence of self-reported spanking history and attitudinal spanking beliefs; (2) determine if a spanking history varies according to gender, sexual identity, or birth cohort; and (3) examine how spanking history, gender, sexual identity, and birth cohort are associated with (a) attitudinal spanking beliefs and (b) the practice of spanking one’s own child.

METHODS: Data were obtained from all Canadian provinces for the 2024 Childhood Adversity and Resilience-Youth and Early Adulthood Research Study (CARe-YEARS; n = 3767; ages 18 to 49 years). Data were analysed using descriptive statistics and logistic regression.

RESULTS: In the sample, 55.6% reported being spanked as a child with the lowest prevalence (48.9%) among the youngest birth cohort. Overall, 22.6% reported that the spanking left a mark or bruise, or caused lasting physical pain and 15.0% believed spanking is necessary to properly raise a child. Several gender, sexual identity, and birth cohort differences were noted.

CONCLUSIONS: Ongoing policies and prevention strategies are needed in Canada to further reduce both the attitudinal belief that spanking is necessary to properly raise a child and the use of spanking in a disciplinary context. An important step in advancing child protection in Canada is to repeal the law permitting spanking and to enhance prevention efforts with a focus on gender and sexual identity.

PMID:41926065 | DOI:10.17269/s41997-026-01190-1

Paediatr Drugs. 2026 Apr 2. doi: 10.1007/s40272-026-00747-4. Online ahead of print.

ABSTRACT

BACKGROUND: Infants and young children with severe atopic dermatitis (AD) have a high burden of disease with a strong impact on quality of life. Here we assess long-term efficacy and safety of dupilumab in pediatric patients aged 6 months to 5 years with severe AD.

METHODS: This is a subgroup analysis of patients aged 6 months to 5 years enrolled in the ongoing LIBERTY AD PED open-label extension (OLE) study of dupilumab who had previously participated in the parent study LIBERTY AD PRESCHOOL part B and had severe AD (Investigator’s Global Assessment [IGA] = 4) at parent study baseline. Patients received weight-tiered dupilumab every 4 weeks (200 mg for patients weighing 5 to < 15 kg; 300 mg for patients weighing 15 to < 30 kg). Key endpoints included the incidence and rate of treatment-emergent adverse events (TEAEs), the proportion of patients with a ≥ 75% improvement in Eczema Area and Severity Index (EASI-75) from parent study baseline, proportions of patients achieving IGA = 0/1 and IGA ≤ 2, and the proportion of patients with a ≥ 6-point improvement in Children’s Dermatology Life Quality Index (CDLQI) for patients aged ≥ 4 years or Infants’ Dermatitis Quality of Life (IDQoL) questionnaire for patients aged < 4 years.

RESULTS: This analysis included 121 patients, of whom 50 completed the week 104 visit. TEAEs were reported in 88% of patients; most TEAEs were mild or moderate and not related to treatment. Common TEAEs included upper respiratory tract infection, nasopharyngitis, and cough. Conjunctivitis events were reported in 19% of patients and were mild or moderate, with a median duration of 8 days. No conjunctivitis event led to treatment discontinuation, and most events resolved during the study. One drug-related event (severe urticaria) led to treatment discontinuation, but it was not serious and resolved over time. Serious TEAEs were reported in 17 patients (14%), including one drug-related pinworm event. No serious TEAE led to treatment discontinuation. By week 4 of the OLE study, patients who had received placebo in the parent study exhibited efficacy improvements comparable to patients who had received dupilumab. By week 104, 96% of patients achieved EASI-75 from parent study baseline, 27% of patients achieved an IGA score of 0/1 (clear/almost clear skin), 92% of patients achieved IGA ≤ 2 (clear skin to mild AD), and the least squares mean percent change in EASI from parent study baseline was – 89%. Additionally, 89% (23/26) of patients achieved a ≥ 6-point (clinically meaningful) improvement in CDLQI, and 100% (3/3) of patients achieved a ≥ 6-point improvement in IDQoL.

CONCLUSION: Long-term treatment with dupilumab for up to 2 years showed acceptable safety and sustained efficacy in signs, symptoms, and quality of life in patients aged 6 months to 5 years with severe AD, with a rapid improvement for patients who had received placebo in the parent study. Long-term safety in the OLE study was consistent with the short-term safety profile observed in the parent study, with no new safety signals detected. [Graphical abstract and plain language summary available] CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

PMID:41926052 | DOI:10.1007/s40272-026-00747-4

Prev Sci. 2026 Apr 2. doi: 10.1007/s11121-026-01897-0. Online ahead of print.

ABSTRACT

Developmental cascade models provide a valuable framework for understanding how risk and protective factors interact over time to shape health and behavioral outcomes. Traditional statistical methods, such as logistic regression and structural equation modeling, have been instrumental in uncovering developmental pathways within prevention science. However, these methods often impose constraints on model complexity and face limitations in capturing the non-linear and interdependent nature of developmental processes. Machine learning (ML) offers complementary advantages, such as the ability to incorporate high-dimensional data, detect complex interactions, and enhance predictive accuracy. These capabilities can improve identification of at-risk individuals, support the timing of interventions across developmental stages, and refine theory-driven models. By integrating ML with developmental cascade models, researchers can more effectively identify when and how which risk accumulates and protective factors exert influence, thereby improving the tailoring and efficiency of prevention strategies. This conceptual paper outlines how ML can extend traditional analytic approaches in developmental cascade research, discusses key practical considerations for researchers including data requirements, software selection, and model validation, and highlights its potential to advance prevention science across the life course.

PMID:41926047 | DOI:10.1007/s11121-026-01897-0

Neurol Ther. 2026 Apr 2. doi: 10.1007/s40120-026-00928-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Fatigue is the most prevalent symptom in “long COVID”, affecting 6-7% of patients after COVID-19 infection. Its pathophysiology remains unclear, with viral persistence, immune dysregulation, and mitochondrial dysfunction among proposed mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulatory approach, has been suggested as a potential treatment.

METHODS: We conducted a randomized, sham-controlled, single-blinded pilot study to evaluate adherence and clinical effects of taVNS in long COVID-related fatigue. Forty-five patients were randomized 1:1:1 to sham stimulation, sub-threshold taVNS, or above-threshold taVNS for 4 weeks using the Conformité Européenne (CE)-certified tVNS-L device (25 Hz, 250 µs, 4 h/day). The primary co-endpoints were fatigue severity (MFI-20) and adherence, defined as mean daily stimulation duration. Secondary endpoints included depressive symptoms (BDI-II), health-related quality of life (SF-36), and post-COVID symptom burden (PCS).

RESULTS: Of 45 enrolled patients (mean age 42.4 years; 73% female), 4 (8.9%) dropped out early. Mean stimulation time was 236 min/day, fulfilling the adherence criterion in > 80% of participants. Adverse events were mild, including skin irritation (6.7%) and vertigo (6.7%). Across all groups, questionnaire scores improved over time; however, no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data.

CONCLUSION: taVNS was safe, feasible, and associated with high adherence in long COVID-related fatigue, but showed no superiority over sham stimulation. Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition.

TRIAL REGISTRATION: The trial was approved by the ethics committee (23/7798) and registered at the German Clinical Trials Register, identifier DRKS00031974.

PMID:41926033 | DOI:10.1007/s40120-026-00928-w

Eur J Neurosci. 2026 Apr;63(7):e70486. doi: 10.1111/ejn.70486.

ABSTRACT

How the brain signals prediction errors for non-rewarding, yet significant, sensory events remains a central question. Although the cortical mismatch negativity provides a well-known signature for deviance detection, the contribution of subcortical dopamine remains unclear. This study tested the hypothesis that phasic dopamine in the nucleus accumbens encodes the salience associated with the violation of an ongoing statistical regularity. Using fiber photometry in freely moving rats, we contrasted an auditory oddball paradigm with a many-standards control. Deviant stimuli elicited a significantly amplified dopamine response compared with standard stimuli. Crucially, this dopamine response enhancement was absent in the control condition, demonstrating that the nucleus accumbens dopamine responds specifically to rule violation rather than mere stimulus rarity. The long latency of this signal (~500 ms) relative to the cortical mismatch negativity argues against a direct role in the initial detection of deviance. Instead, our findings support a model in which subcortical dopamine acts as a distinct salience signal, operating in parallel with cortical deviance detection, to evaluate unexpected events and guide subsequent behavioral adjustments.

PMID:41924943 | DOI:10.1111/ejn.70486

Cancer Rep (Hoboken). 2026 Apr;9(4):e70536. doi: 10.1002/cnr2.70536.

ABSTRACT

BACKGROUND: Physical activity (PA) is associated with improved health outcomes among cancer survivors (CS), yet PA participation and access to PA programs in cancer care are low. Mobile health (mHealth) technologies such as wearable activity trackers and smartphone lifestyle applications are promising strategies to promote PA among CS. However, CS’s adoption patterns and willingness to share resulting mHealth data with healthcare providers are underexplored.

AIMS: This study examined mHealth technology ownership and usage as well as willingness to share wearable data with healthcare providers among CS and identified demographic and health-related correlates.

METHODS: Self-reported data were collected from post treatment CS (n = 518; M_age = 56.5 (SD = 14.5); 54.6% female) from a large healthcare system. Univariate logistic regression models examined associations between demographic (age, sex, race/ethnicity, education, income, marital status, employment status, health status, BMI) and disease (time since diagnosis, treatment received, disease stage) characteristics and meeting PA guidelines (i.e., 150 min/week of moderate to vigorous PA) and activity tracker ownership, lifestyle app usage, and willingness to share wearable data with healthcare providers.

RESULTS: Nearly all CS (97.5%) owned a smartphone. Over half (52.9%) owned an activity tracker, and one-third (32.4%) used a lifestyle app. Most (64.3%) were willing to share wearable data with healthcare providers. Participants with a college degree or higher income, those who met PA guidelines, and those who were obese were more likely to own a wearable activity tracker. Along with those factors, younger age (< 65) and full-time employment were also associated with a higher likelihood of using a lifestyle app (p < 0.05). Being employed full-time was significantly associated with willingness to share data with a healthcare provider. No other relationships were significant.

CONCLUSIONS: Many CS use or are open to using mHealth technologies. However, differences in adoption by demographic characteristics and unclear demographic and disease correlates of willingness to share data highlight the need for targeted, inclusive, and evidence-based strategies to integrate these tools into survivorship care. Understanding who adopts mHealth technologies is essential to optimizing their potential to improve long-term cancer outcomes.

PMID:41924934 | DOI:10.1002/cnr2.70536

Health Promot Int. 2026 Mar 2;41(2):daag045. doi: 10.1093/heapro/daag045.

ABSTRACT

In 2020, Health Canada approved the INSTI human immunodeficiency virus (HIV) self-test. Adoption and distribution of alternative HIV testing interventions, like self-testing, are essential in meeting the United Nations 95-95-95 goals. We explored the acceptability of HIV self-testing among sexual health service providers and Two-Spirit, gay, bisexual, and queer men (2SGBQM). Between 2020 and 2021, peer researchers conducted virtual focus groups (13) and interviews (18) with providers (n = 18) and 2SGBQM (n = 38) across Ontario, Canada, and analysed data using community-based participatory research approach and reflexive thematic analysis. HIV self-testing was highly acceptable among both providers and 2SGBQM. Both groups identified ‘increased access to HIV testing’ as a benefit. Providers identified ‘client empowerment’ and ‘reduced workload for providers’ as other perceived benefits. 2SGBQM highlighted ‘convenience’ as a key benefit and rationale for self-testing, though some expressed concerns and hesitance due to ‘fear of needles/blood’ and ‘perceptions of lower accuracy and reliability’ of self-test results. Providers and 2SGBQM referred to the ‘potential for missed connections to care’, and ‘self-harm’ with positive test results as additional concerns for self-testing. Both groups suggested that first-time or inexperienced testers should be tested in-clinic, compared with experienced or regular testers who may benefit from self-testing. Participants expressed that HIV self-testing should be widely available for free, or a modest fee up to $20 CAD. Providers and 2SGBQM both found HIV self-testing highly acceptable, particularly when self-administered by experienced testers. Clinic-based testing remains important, especially for first-time testers and 2SGBQM who have concerns or hesitance regarding self-testing.

PMID:41924929 | DOI:10.1093/heapro/daag045

Vet Rec. 2026 Apr 2. doi: 10.1002/vetr.70554. Online ahead of print.

ABSTRACT

BACKGROUND: Artificial intelligence (AI) is becoming increasingly prevalent in the modern world, including in veterinary medicine. This cross-sectional study aimed to investigate horse carers’ attitudes towards using AI use in equine care.

METHODS: An online survey was distributed to UK horse owners/carers in 2025, covering participants’ demographics and use of AI and their opinions of AI for equine care. Statistical analysis included descriptive statistics, categorisation of free-text responses and logistic regression to determine factors associated with opinions.

RESULTS: Ninety-seven responses were analysed. Participants had a predominantly positive opinion of AI to automate large datasets for equine care, and a predominantly negative opinion for automating communications and medical decision making. Key categories identified in free-text responses were: AI use in general/equine care, desire for human interaction and AI as a supportive aid only. Positive attitudes towards AI for equine care were significantly associated with participants’ opinions of AI in their own lives (odds ratio [OR]: 3.69, 95% confidence interval [CI]: 3.06‒4.45) and understanding of AI (OR: 1.31, 95% CI 1.03‒1.66).

LIMITATIONS: This is a small exploratory study of horse owners/carers in the UK, and the findings may not be more widely generalisable.

CONCLUSION: Horse owners/carers had mixed opinions on the use of AI in equine care, and their primary concern was around it replacing human decision making.

PMID:41924893 | DOI:10.1002/vetr.70554