Nevin Manimala

J Clin Rheumatol. 2026 Feb 2. doi: 10.1097/RHU.0000000000002322. Online ahead of print.

ABSTRACT

BACKGROUND: Psoriatic arthritis (PsA) shares genetic features with psoriasis (PsO), with HLA-Cw6 being the main risk allele that may shape its clinical phenotype. This study aimed to evaluate the association between HLA-Cw6 status and clinical features, comorbidities, and treatment outcomes in PsA.

METHODS: We conducted a retrospective study of 426 patients with PsA who fulfilled the CASPAR criteria and had documented HLA-Cw6 status. Demographic, clinical, laboratory, and treatment-related variables were extracted from medical records. Patients were compared according to HLA-Cw6 positivity using descriptive, bivariate, and multivariate analyses.

RESULTS: HLA-Cw6 was present in 24.6% of the patients. HLA-Cw6-positive individuals were more frequently female (65.7% vs. 46.1%, P=0.001) and showed earlier PsO onset (28.0 vs. 35.3 y, P=0.009) and longer PsO-arthritis latency (17 vs. 9 y, P=0.024). Dactylitis was significantly less common in HLA-Cw6-positive patients (25.7% vs. 38.0%, P=0.022). HLA-Cw6-positive patients received more targeted therapies (1.8 vs. 1.5 drug classes, P=0.014) and had shorter TNFi persistence (17 vs. 36 mo, P=0.044). IL-12/23 inhibitors showed longer persistence in this group, although the difference was not statistically significant. In multivariate models, HLA-Cw6 was independently associated with female sex (OR: 4.11, P=0.003), lower frequency of dactylitis (OR: 0.33, P=0.020), and greater odds of difficult-to-manage PsA (OR: 12.53, P=0.001) and treatment-refractory PsA (OR: 15.39, P=0.001) based on recent EULAR definitions.

CONCLUSIONS: HLA-Cw6 identifies a PsA subset with distinctive clinical features and increased therapeutic complexity. These findings support the potential of HLA-Cw6 as a biomarker for PsA characterization and individualized therapy.

PMID:41622883 | DOI:10.1097/RHU.0000000000002322

Disabil Rehabil. 2026 Feb 2:1-9. doi: 10.1080/09638288.2026.2621082. Online ahead of print.

ABSTRACT

BACKGROUND: Children with disabilities (CWD) experience greater obstacles than those without disabilities, including increased poverty, reduced healthcare opportunities, minimal educational resources, and stigma. This research explored the impact of community interventions on reducing stigma and discrimination toward children with disabilities.

METHODS: A repeated cross-sectional survey design (2019/2021) was implemented with community members in three low-resource compounds in Lusaka, Zambia, regarding stigma related to disability and participation in sensitization events via Kusumala+, a community-based intervention designed to improve quality of life for households with CWD. The analysis included descriptive statistics and linear regression assessing group mean change over time.

RESULTS: Participants included N = 259 (2019) and N = 1037 (2021). Subscales of stigma were identified: attitudes (t = 9.7, p < 0.001) and discrimination (t = 4.1, p < 0.001), which both significantly changed from baseline to follow-up. The effect size for the change in discrimination was d = 0.28 (95% CI 0.15-0.42) (weak to moderate effect) and for attitudes was d = 0.67(95% CI 0.53-0.81) (strong effect). Attitudes improved if event attendance occurred and increased with each additional event. In contrast, discrimination improved only when one event attendance occurred, not with each additional event change, in adjusted or unadjusted models.

CONCLUSION: Sensitization activities and events show promise as targeted interventions to reduce stigma and discrimination and create supportive community environments for CWD and their families.

PMID:41622874 | DOI:10.1080/09638288.2026.2621082

J Chem Theory Comput. 2026 Feb 2. doi: 10.1021/acs.jctc.5c01498. Online ahead of print.

ABSTRACT

Assessing the time scale of biological processes using molecular dynamics (MD) simulations with sufficient statistical accuracy is a challenging task, as processes are often rare and/or slow events, which may extend largely beyond the time scale of what is accessible with modern day high performance computational infrastructure. Recently, the replica exchange partial path transition interface sampling (REPPTIS) algorithm was developed to study rare and slow events involving metastable states along their reactive pathways. REPPTIS is a path sampling method where paths are cut short to reduce the computational cost, while combining this with the efficiency offered by replica exchange between the partial path ensembles. However, REPPTIS still lacks a formalism to extract time-dependent properties, such as mean first passage times, fluxes, and rates, from the short partial paths. In this work, we introduce a Markov state model (MSM) framework to estimate full path lengths and kinetic properties from the overlapping partial paths generated by REPPTIS. The framework results in newly derived closed formulas for the REPPTIS crossing probability, mean first passage times (MFPTs), flux, and rate constant. Our approach is then validated using simulations of Brownian and Langevin particles on a series of one-dimensional potential energy profiles as well as the dissociation of KCl in solution, demonstrating that REPPTIS accurately reproduces the exact kinetics benchmark. The MSM framework is further applied to the trypsin-benzamidine complex to compute the dissociation rate as a test case of a biological system, albeit the computed rate underestimates the experimental value. In conclusion, our MSM framework equips REPPTIS simulations with a robust theoretical and practical foundation for extracting kinetic information from computationally efficient partial paths.

PMID:41622863 | DOI:10.1021/acs.jctc.5c01498

Nurs Crit Care. 2026 Mar;31(2):e70376. doi: 10.1111/nicc.70376.

ABSTRACT

BACKGROUND: Intensive care unit (ICU) nurses frequently encounter ethical dilemmas, patient death and emotional distress, which can shape attitudes towards end-of-life care. Spiritual coping and psychological flexibility may support nurses’ well-being and caregiving behaviour, but the mechanisms by which these factors affect ICU nurses’ attitudes towards end-of-life care remain underexplored, particularly in Eastern cultural contexts.

AIMS: To examine associations between spiritual coping, psychological flexibility and attitudes towards end-of-life care among ICU nurses, and to test whether psychological flexibility mediates the spiritual coping-attitude relationship.

STUDY DESIGN: A cross-sectional study was conducted between November and December 2024 in a large teaching hospital in China. Participants were selected using convenience sampling, and data were collected using the Chinese versions of the Spiritual Coping Questionnaire, Comprehensive Assessment of Acceptance and Commitment Therapy Processes (CompACT) and the End-of-Life Care Attitude Scale for Medical Workers. Descriptive statistics, group comparisons, Pearson correlations, multiple linear regression and PROCESS (Model 4) bootstrap mediation were used.

RESULTS: A total of 244 ICU nurses were included. Psychological flexibility and spiritual coping were positively correlated with attitudes towards end-of-life care (r = 0.635 and r = 0.282, both p < 0.001). In regression, psychological flexibility (p < 0.001), spiritual coping (p = 0.015), death education (p < 0.001), end-of-life care practice (p < 0.001) and educational level (p = 0.036) were significant predictors; the model explained 67.9% of the variance (R² = 0.679). Bootstrap mediation showed a significant indirect effect of spiritual coping on attitudes via psychological flexibility (indirect effect = 0.118, 95% CI 0.064-0.193), accounting for 48.96% of the total effect.

CONCLUSIONS: ICU nurses with greater spiritual coping report more positive end-of-life care attitudes, partly through higher psychological flexibility. Interventions integrating Acceptance and Commitment Therapy-informed flexibility training with culturally sensitive spiritual support and structured death education may strengthen nurses’ preparedness for end-of-life care.

RELEVANCE TO CLINICAL PRACTICE: Incorporating psychological flexibility and spiritual coping into continuing education could enhance ICU nurses’ resilience and improve end-of-life care quality.

PMID:41622496 | DOI:10.1111/nicc.70376

Neural Regen Res. 2026 Jan 27. doi: 10.4103/NRR.NRR-D-25-00498. Online ahead of print.

ABSTRACT

The pathophysiological mechanism of mild traumatic brain injury remains poorly understood. Generalized q-sampling imaging is applicable to a broad spectrum of diffusion imaging data, provides high-resolution depictions of the brain’s structural connectivity, enables tracking neural fibers across brain regions, and shows promise for predicting neurological outcomes. Graph theory, a quantitative method for modeling complex networks, has been widely used to study changes in brain structure and function. This longitudinal observational study involved 34 patients with acute mild traumatic brain injury (12 men and 22 women) and 31 healthy controls (14 men and 17 women). Clinical and cognitive assessments, and magnetic resonance imaging scans were conducted within 72 hours and at 3 months post-injury. Subsequent graph theory and statistical analyses showed that generalized q-sampling imaging-based structural brain networks captured small-worldness in patients with mild traumatic brain injury compared with healthy controls. Patients with mild traumatic brain injury exhibited cognitive deficits, which showed improvement at the 3-month follow-up. The results also indicated changes in betweenness centrality, node efficiency, and node clustering coefficient of the left fusiform gyrus in patients with chronic mild traumatic brain injury, and an increase in connectivity strength between the bilateral anterior cingulate cortices. Preliminary explanations were made based on neural plasticity and compensatory mechanisms. The underlying mechanisms remain to be further explored in our subsequent research.

PMID:41622453 | DOI:10.4103/NRR.NRR-D-25-00498

Nurs Crit Care. 2026 Mar;31(2):e70359. doi: 10.1111/nicc.70359.

ABSTRACT

This study aimed to examine consumer perceptions and priorities for safety and quality in paediatric intensive care units (PICUs) to inform safety measurement and quality improvement efforts. We conducted a cross-sectional, co-designed survey distributed to PICU parents/caregivers across Australia and New Zealand. Quantitative and qualitative data were collected and analysed using descriptive statistics and inductive content analysis. One hundred and seventeen parents/caregivers identified three key safety themes: foundations for safer care delivery, understanding as a foundation for safety, and shared voices, safer choices. The most frequently selected quantitative measurement priorities by respondents were nurse staffing and communication.

PMID:41622432 | DOI:10.1111/nicc.70359

J Egypt Natl Canc Inst. 2026 Feb 2;38(1):3. doi: 10.1186/s43046-026-00339-w.

ABSTRACT

BACKGROUND: Luminal breast cancer (LBC) is the most common subtype of breast cancer affecting women worldwide. Although luminal breast cancer typically has a better prognosis, it mostly responds poorly to neoadjuvant chemotherapy. Non-coding RNAs, especially long non-coding RNAs and microRNAs are crucial in regulating biological processes that contribute to breast cancer development. MALAT1, a long non-coding RNA, is pivotal in the progression of breast cancer. Epithelial-mesenchymal transition (EMT) is critical for cell movement during embryonic development. Clarifying this role could pave various avenues for developing innovative strategies for combating this subtype of malignancy. The present study aimed to investigate the expression profiles and clinical relevance of MALAT1 level and EMT-related miRNAs (miR-17-5p, miR-20a-5p, miR-93-5p, miR-135b-5p, and miR-146a-5p) alongside EMT markers (E-cadherin, N-cadherin, vimentin, fibronectin, twist, SNAI1, Slug, ZEB1, and ZEB2) in LBC patients.

METHODS: Fresh tissues were collected from fifty patients and twenty noncancerous controls. Differential expression of the markers was evaluated using qRT-PCR assay. Spearman Rho test assessed the relationship between the expression levels. Linear regression test evaluated the correlation between the parameters and various clinico-pathological features.

RESULTS: Our results revealed an overall upregulation of MALAT1 in breast cancer tissues although this increase did not reach statistical significance. Overexpression of miR-20a-5p, miR-135b, and ZEB2 was reported, whereas miR146a-5p, ZEB1 and Vimentin levels were suppressed. Correlation analysis demonstrated that miR-20a-5p was positively correlated with SNAI1, E-cadherin, N-cadherin and Slug also it was significantly associated with family history and tumor laterality.

CONCLUSIONS: Our findings suggest that miR-20a-5p plays an oncogenic role in luminal breast cancer by promoting EMT, while MALAT1 may contribute to disease progression through indirect regulatory mechanisms. Finally, MALAT1 and miR-20a-5p might serve as potential therapeutic and prognostic targets in LBC.

PMID:41622408 | DOI:10.1186/s43046-026-00339-w

Dev Sci. 2026 Mar;29(2):e70127. doi: 10.1111/desc.70127.

ABSTRACT

Declining youth electoral participation threatens the long-term legitimacy of representative democracy. However, timely cross-national indicators of early disengagement remain scarce. This study draws on data from the IEA International Civic and Citizenship Education Study (ICCS) to examine (a) whether eighth-grade students’ stated voting intentions [are associated with] their cohort’s eventual electoral participation, and (b) which individual-level factors best explain those intentions after controlling for country-level characteristics. First, we align students’ voting intentions from IEA ICCS 2009 and 2016 with [corresponding] official age-specific turnout rates in each cohort’s first national election. The analysis reveals a moderate, statistically significant association, indicating that higher proportions of “likely future voters” in Grade 8 are associated with higher turnout once these cohorts reach voting age. Second, to identify the drivers of voting intentions, we pool microdata from all three IEA ICCS cycles (2009, 2016, 2022; N $\approx$ 316,000 students) and estimate fixed-effects models to account for time-invariant national confounders. Results show that students’ political interest emerges as the strongest predictor, followed by civic knowledge, self-efficacy, trust in the political system and its institutions, and parental political interest. Student background characteristics (e.g., gender or language at home) lose statistical significance once these factors are accounted for. The findings validate adolescent voting intentions as an early warning indicator and highlight malleable psychological levers (i.e., interest, knowledge, efficacy) that civic-education policy can target.

PMID:41622400 | DOI:10.1111/desc.70127

J Clin Psychol Med Settings. 2026 Feb 2. doi: 10.1007/s10880-026-10129-0. Online ahead of print.

ABSTRACT

Chronic pain (CP) and hazardous/harmful drinking (HD) commonly co-occur. HD contributes to the onset and severity of CP, while CP severity predicts alcohol use disorder relapse. Integrated treatments for CP and HD are needed in rural areas, where CP and alcohol-related consequences occur at higher rates and treatment accessibility is lower. This study assessed the acceptability and feasibility of an app-based cognitive-behavioral intervention for CP and HD. Participants (n = 32) were rural residents reporting CP and HD (mean age = 49.81, SD = 8.79). Participants were randomized to intervention or assessment-only control. Self-report questionnaires at baseline and 12-week follow-up assessed program acceptability, pain, alcohol involvement, and functioning. Timely recruitment and low attrition (3.2%) supported procedure feasibility, while app engagement suggested intervention feasibility and acceptability. Descriptive statistics suggest reductions in pain (37% reduction in median pain in intervention group vs. 10% in control group). Changes in alcohol-related behavior were not consistent across outcomes and warrant further study (e.g., no change in median heavy drinking episodes in intervention, with 77% reduction in control; 60% reduction in alcohol consequences in intervention vs. 27% in control). This mobile intervention is feasible and acceptable for rural residents and may help address CP and functioning among those who engage in HD.

PMID:41622395 | DOI:10.1007/s10880-026-10129-0

J Bone Miner Metab. 2026 Feb 1. doi: 10.1007/s00774-025-01682-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Though low serum magnesium (Mg) levels are associated with adverse outcomes in patients on haemodialysis, the interaction with calcimimetics remains uncertain. We hypothesized a potential interaction between serum Mg levels and calcimimetic use in cardiovascular events (CVEs), all-cause mortality, and new fractures during follow-up in patients on haemodialysis.

MATERIALS AND METHODS: This single-centre retrospective cohort included 399 Japanese adults on maintenance haemodialysis, followed for ≤ 5 years. Cox models with time-dependent serum Mg levels and calcimimetic usage interaction adjusted for clinicodemographic and biochemical covariates.

RESULTS: At baseline, 205 patients (51.4%) were prescribed calcimimetics (median serum Mg, 2.5 mg/dL). The mean observational period was 40.6 months, and 122 CVEs, 159 all-cause mortality, and 69 new fractures occurred (incidence rates: 0.09, 0.10-, and 0.05 per patient-year), respectively. The time-dependent model showed serum Mg < 2.4 mg/dL was associated with a markedly higher risk for new fractures in calcimimetic-naïve patients. Serum Mg levels were not significantly associated with CVEs and all-cause mortality, regardless of calcimimetic usage. The restricted cubic spline curve demonstrated linear inverse trends of serum Mg levels with all-cause mortality and new fractures in calcimimetic-naïve patients. However, no significant interaction between Mg and calcimimetic use was observed for any outcome.

CONCLUSION: We did not detect a statistically significant interaction between serum Mg levels and calcimimetic use. Nonetheless, low serum Mg (< 2.4 mg/dL) was associated with a higher risk of fractures, particularly among calcimimetic-naïve patients. Thus, low serum Mg is a potentially modifiable risk marker associated with fracture risk, particularly in calcimimetic-naïve patients.

PMID:41622380 | DOI:10.1007/s00774-025-01682-z