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Whole transcriptome analysis reveals differential gene expression associated with Anaplasma phagocytophilum invading HL-60 cells

Parasit Vectors. 2026 May 8. doi: 10.1186/s13071-026-07381-6. Online ahead of print.

ABSTRACT

BACKGROUND: Anaplasma phagocytophilum is an obligate intracellular, tick-borne bacterial pathogen capable of causing disease and even mortality in various mammals, including humans. Non-coding RNAs play important regulatory roles in multicellular organisms, including innate and adaptive immune pathways, which control bacterial, parasitic, and viral infections. However, the global transcriptomic landscape encompassing both ncRNAs and mRNAs in HL-60 cells invaded by A. phagocytophilum remains unexplored.

METHODS: Cell apoptosis was evaluated by flow cytometry at multiple time points after HL-60 cell infection with A. phagocytophilum. Total RNA was extracted and analyzed by RNA sequencing (RNA-seq) to delineate expression alterations of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) at 24 h post-infection (hpi). Bioinformatics methods were employed for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to elucidate the potential functions of these differentially expressed genes. Furthermore, an integrated bioinformatics approach was applied to systematically construct a competing endogenous RNA (ceRNA) network involving lncRNAs, miRNAs, and mRNAs.

RESULTS: A. phagocytophilum infection accelerated HL-60 cell apoptosis at multiple time points, with the most significant effect observed at 24 hpi. Transcriptome profiling at 24 hpi identified substantial differential expression, including 487 lncRNAs, 550 mRNAs, and 22 miRNAs with statistically significant changes in expression. Then, expression patterns of eight lncRNAs, eight mRNAs, and seven miRNAs were experimentally validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR), demonstrating strong correlation with RNA-seq results. Bioinformatics analyses revealed significant enrichment of differentially expressed mRNAs in three key pathways: the PI3K/Akt signaling pathway, the actin cytoskeleton regulation pathway and the p53 signaling pathway. Differentially expressed lncRNAs were largely related to the phospholipase D signaling pathway and pathways related to cortisol and aldosterone synthesis/secretion. The altered miRNAs showed predominant enrichment in Rap1 and NF-κB signaling pathways. Notably, computational reconstruction of the lncRNA-miRNA-mRNA ceRNA network identified hsa-miR-4518 and hsa-miR-3609 as central regulatory nodes.

CONCLUSIONS: This comprehensive transcriptome study elucidates complex gene regulatory networks activated in HL-60 cells after A. phagocytophilum invasion, with particular emphasis on pathogen-modulated miRNA signatures that coordinate critical pathways governing host immune responses and microbial survival strategies. These findings elucidate previously uncharacterized molecular mechanisms underlying A. phagocytophilum pathogenesis and may provide actionable targets for novel therapeutics.

PMID:42104495 | DOI:10.1186/s13071-026-07381-6

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Large-sized grafts versus standard-sized grafts combined with anterolateral ligament reconstruction in ACL-deficient knees: a randomized controlled trial

Knee Surg Relat Res. 2026 May 8;38(1):20. doi: 10.1186/s43019-026-00321-9.

ABSTRACT

BACKGROUND: Anterior cruciate ligament (ACL) injuries are highly prevalent among athletes and continue to pose challenges owing to persistent instability and variable return-to-sport outcomes following reconstruction. Anterolateral ligament (ALL) reconstruction and has been introduced to improve outcomes. Increasing graft diameter was described to enhance biomechanical properties. This study hypothesis was, that ACL reconstruction (ACL-R) combined with ALL reconstruction is superior to a large-sized graft ACL-R.

PURPOSE: To compare outcomes of large-sized (six-strand) hamstring grafts with those of standard-sized (four-strand) grafts combined with anterolateral ligament (ALL) reconstruction in ACL-deficient knees.

METHODS: A total of 82 patients (18-45 years) undergoing ACL reconstruction were randomized to either a large (six-strand) hamstring graft group (group A, n = 41) or a standard-sized (four-strand) graft plus ALL reconstruction group (group B, n = 41). Primary outcomes were knee stability (pivot-shift and Lachman tests) and functional scores [Lysholm and International Knee Documentation Committee (IKDC) scores]. Secondary measures included pain scores, return to sport, and complication rates, with follow-up at 24 months.

RESULTS: The mean diameter of the large-sized graft was 9.5 ± 2.5 mm, while the mean diameter of the standard-sized graft was 8.0 ± 2.0 mm. Both groups demonstrated significant gains in stability and function. Lysholm scores improved from 51 to 94 in group A and from 56 to 98 in group B with no significant difference between both groups (p = 0.418), while IKDC scores rose from 37 to 88 and from 37 to 91, respectively and it was significantly higher in group B (p = 0.036). Negative pivot-shift was observed in 87.8% of group A and 90.2% of group B with no significant intergroup difference (p = 0.841). Return-to-sport at 12 months was 93.5% and 96.1%, respectively with no significant difference (p = 1.00). Graft rupture occurred in 4.8% of group A and 2.4% of group B. Overall complications were low and statistically comparable (p = 1.00).

CONCLUSIONS: Both large hamstring grafts and standard grafts augmented with ALL reconstruction provided significant functional and stability improvements, with no major differences between techniques.

PMID:42104476 | DOI:10.1186/s43019-026-00321-9

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Comparative analysis of bariatric surgery outcomes and preoperative body composition in individuals with obesity with and without binge-eating disorder: a retrospective study

J Eat Disord. 2026 May 9. doi: 10.1186/s40337-026-01628-4. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare preoperative metabolic parameters and body composition in individuals with obesity with and without binge-eating disorder (BED), and to evaluate postoperative short-term weight-loss outcomes in these two groups in the absence of structured preoperative cognitive-behavioral therapy (CBT).

METHODS: This retrospective analysis included 302 participants with obesity from the Western China Bariatric Surgery Cohort. Participants were classified into the BED group and the group without BED based on the Binge Eating Scale (BES) questionnaire and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria. Basal metabolic parameters were assessed via an InBody 770 body composition analyzer, and rigorous follow-up tracking of postoperative weight variations was performed.

RESULTS: A total of 302 individuals with obesity were included, with 151 participants in the BED group and 151 in the group without BED. The proportion of females was significantly higher in the BED group than in the group without BED (p = 0.023). After adjustment for sex, there were no significant between-group differences in preoperative glucose, triglyceride, or total cholesterol levels. Sex hormone levels were comparable between groups in both males and females. Analysis of body composition showed no group differences in overall body weight, BMI, visceral fat area, or basal metabolic rate; however, females with BED exhibited greater leg fat mass (p = 0.037), while a trend toward a larger thigh circumference was observed among males (p = 0.050). In the linear mixed-effects model adjusted for sex and baseline weight, neither the main effect of group nor the group × time interaction was statistically significant, indicating comparable postoperative weight trajectories between the BED and NBED groups from baseline to 2 years after surgery.

CONCLUSION: Individuals with obesity with and without BED showed largely comparable body-composition and metabolic characteristics. Bariatric surgery was associated with similar short-term weight-loss outcomes in individuals with obesity with and without BED, even in the absence of structured preoperative cognitive-behavioral therapy. These findings suggest that bariatric surgery may be an effective short-term weight-loss intervention for individuals with obesity and binge-eating disorder.

PMID:42104469 | DOI:10.1186/s40337-026-01628-4

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Proteomic analysis in Alzheimer’s disease and other dementias: a focus on sex-specific differences

Alzheimers Res Ther. 2026 May 8. doi: 10.1186/s13195-026-02068-7. Online ahead of print.

ABSTRACT

BACKGROUND: Fluid protein studies in cerebrospinal fluid (CSF) and plasma have provided important insights into neurodegenerative dementias; however, there is a limited investigation of sex-related differences and cross-biofluid relationships. In Alzheimer’s disease (AD), Lewy body dementia (LBD), and frontotemporal dementia (FTD), large-scale, sex-stratified analyses of paired CSF and plasma samples remain scarce. Using the multiplex and ultrasensitive capabilities of NULISAseq™ technology, this study aims to characterize sex- and disease-specific proteomic alterations associated with Central Nervous System (CNS) pathology to explore underlying mechanisms.

METHODS: CSF and plasma samples from 359 individuals with AD, LBD, FTD, and cognitively healthy controls were analyzed using the NULISAseq™ CNS Disease Panel 120. Differential protein expression analyses were conducted across diagnoses and stratified by sex, adjusting for relevant covariates. Spearman’s correlation analyses were performed to assess concordance between CSF and plasma protein levels. All statistical analyses were conducted in R v4.4.3.

RESULTS: Differential protein expression analyses across diagnoses revealed two potential transdiagnostic biomarkers: ICAM1 in CSF and ANXA5 in plasma, showing consistent increases across AD, LBD, and FTD. Sex-stratified analyses in CSF showed modest changes, including higher CCL26, ANXA5, and IL10 in females with AD, and higher IL9, PRDX6, and CX3CL1 in males with AD. In LBD, females exhibited upregulation of ACHE, SFRP1, POSTN in both CSF and plasma. NPTX1 was identified as a potential CSF biomarker for FTD, showing downregulation particularly in males. In contrast, analyses stratified by sex in plasma displayed a larger number of proteins across all dementias, with females showing a higher number of upregulated inflammation-related proteins predominantly involved in cytokine signaling. Overall cross-fluid correlations were restricted to a small subset of proteins, indicating compartment-specific regulation.

CONCLUSIONS: This study represents a large-scale, sex-stratified proteomic analysis of CSF and plasma across major neurodegenerative dementias using NULISAseq™ technology. The findings highlight sex-dependent biomarker patterns, particularly in plasma, and underscore the importance of incorporating sex as a biological variable in dementia research. Future studies should validate candidate proteins in independent cohorts, investigate their functional and mechanistic roles, and assess their utility for biomarker development and sex-tailored therapeutic strategies.

PMID:42104459 | DOI:10.1186/s13195-026-02068-7

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The relationship between aging anxiety, job stress and psychological resilience in oncology nurses: a cross-sectional study

BMC Psychol. 2026 May 9. doi: 10.1186/s40359-026-04716-x. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer is one of the leading causes of death worldwide. Oncology nurses play an essential role in the care of oncology patients. Providing care for cancer patients and managing complex treatment processes can be challenging for oncology nurses. The psychological effects of caring for cancer patients and facing their illness and death are often overlooked. The relationships between aging anxiety, job stress, and psychological resilience remain unclear. The aim of this study was to determine the relationship between aging anxiety, job stress, and psychological resilience in oncology nurses.

METHODS: This cross-sectional, correlational and descriptive study was conducted with 220 nurses working in an oncology hospital from December 2023 to February 2024. The Personal Information Form, Relational Aging Anxiety Scale (RASS), Nurse Stress Scale (NSS), and Resilience Scale for Nurses (RSN) were used to collect the data. Descriptive analyses, correlation analysis, and Structural Equation Modeling (SEM) were performed.

RESULTS: Correlation analyses revealed a statistically significant low positive correlation between the relational aging anxiety subscale and NSS scores (r = 0.240, p < 0.05), and a low negative correlation with RSN scores (r = – 0.182, p < 0.05). SEM indicated that RAAS scores were a significant negative predictor of RSN scores (β = -0.214, p < 0.05) and a significant positive predictor of NSS scores (β = 0.608, p < 0.05). No significant direct effect between RSN and NSS scores (β = -0.007, p > 0.05).

CONCLUSIONS: These findings suggest that higher aging anxiety among nurses is associated with greater stress and lower psychological resilience, highlighting the need for comprehensive training programs to reduce aging anxiety and job stress, and to enhance psychological resilience among oncology nurses. Interventions focusing on stress management, emotional regulation, and self-care are recommended. Experimental studies to evaluate the effectiveness of these interventions are encouraged.

PMID:42104429 | DOI:10.1186/s40359-026-04716-x

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Cyclosporine A promotes renal fibrosis through activating endoplasmic reticulum stress by targeting miR-212-5p/ATF6 axis

J Transl Med. 2026 May 8. doi: 10.1186/s12967-026-08252-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Cyclosporine A (CsA) is a widely used immunosuppressive drug, but its long-term use is associated with renal fibrosis. Despite its clinical importance, the molecular mechanisms underlying CsA-induced renal fibrosis remain poorly understood.

METHODS: We used C57BL/6 mice (n = 6 per group) treated with CsA (30 mg/kg/day, gavage) and Boston University mouse proximal tubular (BUMPT) cells (n = 6 per group) exposed to CsA (8 µM). Assessments included Masson’s trichrome staining, Western blot, quantitative real-time PCR, immunohistochemistry, and in situ hybridization. Mechanistic studies employed miR-212-5p mimics and inhibitors, activating transcription factor 6 (ATF6) overexpression, and the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid (4-PBA). Data are presented as mean ± standard deviation; statistical significance was defined as p < 0.05.

RESULTS: CsA induced significant renal fibrosis in vivo and in vitro, evidenced by increased collagen deposition and elevated expression of alpha-smooth muscle actin (α-SMA), fibronectin, collagen type I and IV, and key profibrotic factors (p < 0.05). RNA analysis revealed that miR-212-5p was markedly upregulated in CsA-treated kidneys, predominantly in renal tubules. Concurrently, ATF6, a protective component of the unfolded protein response (UPR), was significantly downregulated. Bioinformatics prediction and luciferase reporter assays confirmed that miR-212-5p directly targets the 3′ untranslated region of Atf6 mRNA. Functionally, miR-212-5p mimic exacerbated CsA-induced ATF6 suppression and fibrosis, whereas anti-miR-212-5p restored ATF6 expression, attenuated ER stress, and significantly reduced fibrotic markers. Similarly, ATF6 overexpression or ER stress inhibition with 4-PBA ameliorated CsA-induced fibrosis.

CONCLUSIONS: Our findings position miR-212-5p as a previously unrecognized molecular target of CsA and establish the miR-212-5p/ATF6 axis as a central driver of CsA-induced nephrotoxicity. The findings provide new insights into the molecular mechanisms of CsA nephrotoxicity and identify a potential therapeutic target for preventing CsA-induced renal fibrosis.

PMID:42104426 | DOI:10.1186/s12967-026-08252-5

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Income dynamics and risk of early-onset dementia: a nationwide cohort study

Alzheimers Res Ther. 2026 May 8. doi: 10.1186/s13195-026-02067-8. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between income dynamics-including sustained income level, income changes, and income variability-and early-onset dementia (EOD) has not been well established. This study investigated the association between income dynamics and the risk of EOD.

METHODS: This cohort study included 2,247,461 adults aged 40-60 years who underwent health examinations in 2012 through the Korean National Health Insurance Service, with a median follow-up duration of 5.4 years till 2018. Income status was assessed for 2012 and the 4 preceding years using monthly health insurance premiums, and income-related parameters were derived from this pre-baseline 5-year window. Income variability was defined as the intra-individual standard deviation of four consecutive annual percentage changes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to evaluate the relationship between income dynamics and EOD risk, adjusting for potential confounders.

RESULTS: Sustained low-income status over five years was associated with an increased risk of EOD (HR for 5 years vs. 0 years 1.63, 95% CI 1.49-1.78; P-trend < 0.001), whereas sustained high-income status was associated with a reduced EOD risk (HR for 5 years vs. 0 years 0.55, 95% CI 0.51-0.59; P-trend < 0.001). Notably, higher income variability was linked to a greater risk of EOD (HR for highest vs. lowest quartile 1.37, 95% CI 1.28-1.48; P-trend < 0.001). The decline in income-particularly to the lowest level (Medical Aid beneficiaries)-was associated with an elevated risk of EOD, irrespective of the initial income status.

CONCLUSIONS: Sustained low income, income decline, and greater income variability were associated with higher EOD risk. These findings may help identify socioeconomically vulnerable middle-aged adults for targeted dementia risk assessment and prevention.

PMID:42104420 | DOI:10.1186/s13195-026-02067-8

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Machine learning and SHAP interpretation to identify high-level compassion fatigue among operating room nurses: a multicenter cross-sectional study

BMC Nurs. 2026 May 8. doi: 10.1186/s12912-026-04728-3. Online ahead of print.

ABSTRACT

BACKGROUND: Operating room nurses (ORNs) are at high risk for compassion fatigue (CF), which significantly impairs individuals’ well-being, undermines the stability of the nursing workforce, and jeopardizes patients’ safety. The study aimed to analyze the prevalence and symptom characteristics of CF among ORNs, construct and compare predictive models using machine learning, and determine the relative contribution of distinct features to the models.

METHODS: This is a multi-center cross-sectional study. The questionnaires used in the study included a sociodemographic questionnaire, the Professional Quality of Life Scale (ProQoL), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Pittsburgh Sleep Quality Index (PSQI). LASSO regression was used to select critical variables, and predictive models such as decision tree, logistic regression, random forest, SVM, and XGBoost were constructed and compared. SHapley Additive exPlanation (SHAP) were drawn to show the contribution of each feature to the models. SPSS version 26.0 and R software version 4.4.0 were used for statistical analyses.

RESULTS: In this study, a total of 1024 ORNs from 20 cities across China were recruited. According to ProQoL, 326 (31.8%) reported severe CF, 311 (30.4%) moderate CF, and the remaining 387 (37.8%) no or mild CF. Among the three dimensions, the incidence of secondary traumatic stress was most common (95.4%), followed by low compassion satisfaction (61.3%) and burnout (35.0%). In five machine learning-based predictive models, the RF model stood out with the highest AUC at 0.851 (95%CI: 0.795-0.907) in testing set. Following closely, the XGBoost model showed favorable efficacy with the AUC at 0.824 (95%CI: 0.769-0.879) in testing set, outperforming the remaining algorithms. The results of the two SHAP plots (RF and XGBoost) were consistent: depression, anxiety, self-mental health training, sleep quality, and length of service emerged as the five most significant contributors to the models.

CONCLUSION: This study identified severe CF among ORNs, and the most serious symptom was secondary traumatic stress. The RF model exhibited the best performance in identifying high-level CF among ORNs, and SHAP improved the interpretability of the model. The findings of this study could help medical managers and researchers better understand CF and provide timely interventions for ORNs.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:42104411 | DOI:10.1186/s12912-026-04728-3

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Cultural adaptation and psychometric evaluation of the CHU-9D in Hong Kong adolescents

Health Qual Life Outcomes. 2026 May 8. doi: 10.1186/s12955-026-02549-1. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to perform a cultural adaptation of the Child Health Utility 9D (CHU-9D), a health-related quality of life (HRQoL) instrument, into Traditional Chinese specifically for use in Hong Kong, and evaluating its psychometric properties among a sample of local adolescents.

METHODS: A cross-sectional survey design was employed for data collection. Adolescents aged 13 to 17 years were recruited from diverse local community settings to complete a self-administered questionnaire that included the adapted CHU-9D and relevant demographic items. Psychometric evaluations encompassed assessments of ceiling and floor effects, factorial validity through confirmatory factor analysis, convergent validity via correlation analysis, and known-group validity to examine differences across predefined risk groups.

RESULTS: A total of 627 adolescents successfully completed the survey, providing a robust dataset for analysis. The unidimensionality of the CHU-9D was confirmed, demonstrating excellent model fit indices. A ceiling effect was observed, with 27% of participants reporting full health status on the CHU-9D descriptive system, indicating potential limitations in capturing variations at the upper end of health. Convergent validity was supported by significant correlations between CHU-9D and conceptually relevant items and subscales from another HRQoL instrument. The instrument exhibited strong known-group validity, effectively discriminating HRQoL differences across various risk groups with statistically significant results.

CONCLUSION: The culturally adapted Traditional Chinese version of the CHU-9D demonstrates sound psychometric properties in Hong Kong adolescents, supporting it as a valid tool for measuring and valuing HRQoL in this population and cultural context.

PMID:42104409 | DOI:10.1186/s12955-026-02549-1

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The ecoepidemiology of cutaneous leishmaniasis in Ethiopia: a systematic review and meta-analysis

Parasit Vectors. 2026 May 9. doi: 10.1186/s13071-026-07376-3. Online ahead of print.

ABSTRACT

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical skin disease. In Ethiopia, CL is a public health concern; about 29 million people are at risk, with an estimated incidence of up to 50,000 new cases annually. In endemic communities, access to diagnosis, treatment, and prevention is crucial but often limited. Understanding the prevalence and access to care, as well as exploring its relationship to agroecological factors, is crucial to inform control strategies.

OBJECTIVES: The aim of this work is to estimate the pooled prevalence, access to care service facilities, and spatial distribution and relationship to agroecological factors.

METHODS: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) framework. The metafor and metadata packages from R Studio were used to obtain pooled prevalence and odds ratio using a random-effects model with a double arcsine transformation. The CL endemicity at the woreda level was overlaid with the locations of CL treatment centers and agroecological zones using ArcGIS.

RESULTS: The pooled prevalence of CL was 6.75% (95% confidence interval (CI) 3.37-11.17). Sociodemographic factors (male gender, rural living) and environmental factors (muddy walls, outdoor sleeping, proximity to rocky habitats, and hyrax populations) were significantly associated with CL. CL cases were reported from 85 woredas with a broad spatial distribution; a higher proportion of them were from the Weyna Dega, Dega, and Upper Kola agroecological zones. Access to care is generally poor, with service centers for CL often centralized at the zone level.

CONCLUSIONS: The estimated pooled prevalence likely underrepresents the true burden of CL. The identified risk factors are more related to rural livelihoods and living conditions, and most of the endemic woredas are in the most productive agrarian agroecological zones, which underlines the health and socioeconomic significance of CL in Ethiopia. Thus, decentralizing healthcare services and improving surveillance for CL are crucial steps in breaking the vicious cycle of poverty.

PMID:42104399 | DOI:10.1186/s13071-026-07376-3