Category: Statistics

Tissue Eng Regen Med. 2025 Nov 24. doi: 10.1007/s13770-025-00765-2. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) exhibit therapeutic potential in regenerative medicine. However, their properties, including transcriptomic profiles, vary based on tissue origin, passage stage, and isolation method, complicating their clinical standardization. Addressing these unresolved differences requires comprehensive approaches, such as RNA sequencing, to analyze transcriptomic profiles in detail.

METHODS: In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UC MSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3-4) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identified, followed by transcription factor (TF) and pathway analyses.

RESULTS: Fetal MSCs (UC and smumf cells) exhibited distinct transcriptomic profiles compared to adult MSCs (BM and AD), with 2,208 upregulated and 2,594 downregulated DEGs. Key transcription factors, such as E2F1 and NF-κB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-α signaling, were enriched in fetal MSCs. smumf cells demonstrated transcriptomic stability between early and late passages, with only 12 DEGs identified. Additionally, smumf cells showed enhanced innate immune responses and cholesterol metabolism compared to enzymatically isolated UC MSCs.

CONCLUSION: This study provides a comprehensive transcriptomic comparison of MSCs, highlighting the superior transcriptional stability, immunomodulatory capacity, and metabolic flexibility of fetal MSCs, particularly smumf cells. These findings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application.

PMID:41284123 | DOI:10.1007/s13770-025-00765-2

Lasers Med Sci. 2025 Nov 24;40(1):492. doi: 10.1007/s10103-025-04756-6.

ABSTRACT

Peri-implantitis is one of the most important complications related to dental implants, and there is still no consensus about a protocol for treatment. This study aimed to compare an antimicrobial photodynamic therapy protocol using methylene blue or toluidine blue O, and the efficacy of these two dyes without light activation against human oral biofilm associated with peri-implantitis. Twenty-four dental implants (Classic-CI^®, Systhex Dental Implants) were divided into six groups (n = 4): NC – sterile implants (negative control); PC – contaminated implants (positive control); MB – contaminated implants, decontaminated with methylene blue (0.01%, 1 min); aPDT MB – contaminated implants, decontaminated with antimicrobial photodynamic therapy (MB + red laser); TBO – contaminated implants, decontaminated with toluidine blue O (0.01%, 1 min); aPDT TBO – contaminated implants, decontaminated with antimicrobial photodynamic therapy (TBO + red laser). Microbiologic analysis was performed by counting the colony-forming units (CFUs). Statistical analysis used One-way ANOVA test and Tukey post-test to compare the experimental groups, with a significant level of 5%. Both groups treated with antimicrobial photodynamic therapy were similarly effective against the biofilm, compared to group C (p < 0.001). Dyes alone were similar (p = 0.518) and had no antimicrobial effect. The antimicrobial photodynamic therapy protocol was effective in implant decontamination in vitro regardless of the photosensitizer used, and the dyes without light activation do not seem to be an indicated method for this purpose.

PMID:41284122 | DOI:10.1007/s10103-025-04756-6

Clin Exp Nephrol. 2025 Nov 24. doi: 10.1007/s10157-025-02791-9. Online ahead of print.

ABSTRACT

BACKGROUND: The role of Janus kinase (JAK) 2 in chronic kidney disease (CKD) remains unreported. This Mendelian randomisation (MR) study investigates the causal associations of JAK2 with CKD and provides references for the identification of possible therapeutic targets and the prevention of renal dysfunction.

METHODS: Summary data for JAK2 and various CKD endpoints are extracted from genome-wide association study findings provided by the MRC Integrative Epidemiology Unit and FinnGen. The causal relationships are assessed using inverse variance weighted estimates, weighted median and MR-Egger regression. To ensure rigour, reverse MR, radial MR and leave-one-out approaches are employed for sensitivity analyses, with Cochran’s Q used to assess heterogeneity.

RESULTS: Inverse variance weighted estimates indicate potential two-way causal associations between JAK2 and membranous nephropathy (MN) (odds ratio [OR] = 1.138, 95% confidence interval [CI]: 1.073-1.206; reverse causal association: OR = 1.040, 95% CI: 1.002-1.079). Sensitivity analyses demonstrate that these relationships are relatively robust. An underlying causal relationship between JAK2 and estimated glomerular filtration rate is identified (OR = 0.996, 95%CI 0.993-1.000); however, this becomes non-significant after the radial MR test (P > 0.05). In addition, polycystic kidney disease exhibits a potential causal relationship with JAK2 (OR = 1.066, 95%CI 1.009-1.127).

CONCLUSIONS: Elevated relative expression of JAK2 may represent a potential risk factor for the occurrence of MN. Conversely, patients with MN may exhibit high relative expression of JAK2. These two-way causal associations may inform future efforts aimed at the prevention of CKD and the identification of possible therapeutic targets.

PMID:41284113 | DOI:10.1007/s10157-025-02791-9

Biogerontology. 2025 Nov 24;27(1):10. doi: 10.1007/s10522-025-10352-6.

ABSTRACT

Bone marrow exhibits functional decline, yet cellular heterogeneity and molecular mechanisms remain unclear due to limitations of traditional research methods. This study aims to characterize age-related changes and identify key drivers in bone marrow. Integrated multi-omics analysis was performed using scRNA-seq, proteomics, pseudo-bulk transcriptomics, weighted gene co-expression network analysis (WGCNA)-based transcription factor (TF) network modeling, and CellChat analysis. Samples included 6 young and aged bone marrow specimens. Statistical validation involved differential expression analysis, Cox regression modeling, and receiver operating characteristic (ROC) curve analysis. A novel hematopoietic subpopulation (3.19% of aged samples) was identified, activating the cellular senescence pathway (KEGG) and enhancing inflammatory crosstalk with CD8⁺ T cells via NMU signaling (|avg_log2FC|> 0.58, p < 0.001). Pseudo-bulk and proteomic analyses identified CAPN1, MAP2K1, and JUND as potential signal modules. Immunohistochemistry and Western blot confirmed their co-expression, while molecular docking revealed interaction interfaces. In two independent bulk-RNA cohorts (n = 58), a Cox model based on the CAPN1-MAP2K1-JUND module showed robust predictive value for aging, with AUCs of 0.7507 (p = 0.0154) and 0.90 (p = 0.0274). This study identifies a pivotal molecular module linking single-cell dynamics to tissue-level senescence in bone marrow, providing new insights into aging mechanisms and potential therapeutic targets.

PMID:41284112 | DOI:10.1007/s10522-025-10352-6

Hernia. 2025 Nov 24;30(1):23. doi: 10.1007/s10029-025-03539-w.

ABSTRACT

PURPOSE: Pre-existing comorbidities may negatively impact surgical outcomes, yet risk profiles based on combinations of comorbidities are underutilized. We aimed to identify comorbidity clusters associated with adverse surgical outcomes after inguinal or ventral hernia repair.

METHODS: We performed a retrospective cohort study using the ACS-NSQIP database (2016-2023). Adults undergoing elective inguinal or ventral hernia repair were identified using CPT and ICD-10 codes. Latent class analysis (LCA) identified subgroups of patients who shared similar patterns of comorbidities. Outcomes included postoperative complications, hospital length of stay, and 30-day mortality.

RESULTS: Among 224,522 patients, LCA identified six profiles: no comorbidities, smoking, bleeding disorder or congestive heart failure (CHF), obesity with diabetes or smoking, obesity without diabetes or smoking, and hypertension. Compared with no comorbidities, risk of complications was higher in the smoking (OR 1.32, 95% CI 1.18-1.49), bleeding disorder or CHF (OR 1.68, 95% CI 1.23-2.29), obesity with diabetes or smoking (OR 1.41, 95% CI 1.25-1.58), obesity without diabetes or smoking (OR 1.17, 95% CI 1.06-1.29), and hypertension (OR 1.16, 95% CI 1.05-1.28) clusters. These clusters also had longer hospital stays compared to patients with no comorbidities. 30-day mortality was significantly increased in the “bleeding disorder or CHF” (OR 3.22, 95% CI 1.52-6.84) and hypertension (OR 1.66, 95% CI 1.09-2.54) clusters.

CONCLUSION: Distinct comorbidity clusters predict complications, prolonged hospitalization, and mortality following hernia repair. Incorporating comorbidity profiles into preoperative risk stratification may enhance surgical decision-making, allow targeted interventions, and improve outcomes in high-risk patients.

PMID:41284100 | DOI:10.1007/s10029-025-03539-w

J Magn Reson Imaging. 2025 Nov 24. doi: 10.1002/jmri.70183. Online ahead of print.

ABSTRACT

BACKGROUND: Silicosis is an occupational lung disease characterized by inflammation and fibrosis. As it is irreversible, early identification of high-risk individuals is clinically important, but biomarkers for progression remain lacking.

PURPOSE: To determine whether ventilation and perfusion defects quantified by phase-resolved functional lung (PREFUL) MRI can predict silicosis progression.

STUDY TYPE: Prospective.

SUBJECTS: Thirty participants with silicosis (29 males and 1 female) and 30 healthy controls (29 males and 1 female).

SEQUENCE: 2D spoiled gradient echo, 3.0 T.

ASSESSMENT: All participants underwent baseline PREFUL MRI, pulmonary function tests (PFTs), and chest CT, with quantitative calculation of ventilation defect percentages (VDP_RVent and VDP_FVL-CM) and perfusion defect percentage (QDP). Silicosis was followed for 1 year with assessments including forced vital capacity percent predicted (FVC% predicted), diffusing capacity of the lungs for carbon monoxide percent predicted (DL_co% predicted), symptoms, and CT. Disease progression was defined by any two of: (a) CT evidence of progression, (b) worsening symptoms, or (c) ≥ 10% decline in FVC% predicted or ≥ 15% decline in DLco% predicted.

STATISTICAL TESTS: Spearman correlation coefficients were used to evaluate the correlation between ventilation/perfusion metrics and PFT parameters. Receiver operating characteristic (ROC) curves were used to assess the ability of PREFUL MRI parameters to classify disease progression, reporting the area under the curve (AUC), sensitivity, and specificity. Significance was set at p < 0.05.

RESULTS: Eight patients progressed and 22 remained stable. Baseline VDP_RVent, VDP_FVL-CM, and QDP were significantly higher in progressors (36%, 34%, 40%) than in non-progressors (22%, 15%, 22%). QDP showed strong predictive performance with AUC of 0.72 (95% CI: 0.51-0.93) for radiological progression, 0.90 (95% CI: 0.79-1.00) for PFTs decline, and 0.97 (95% CI: 0.92-1.00) for global progression.

DATA CONCLUSION: Increased ventilation and perfusion defects on PREFUL MRI are associated with silicosis progression.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

TRIAL REGISTRATION: NCT06431555.

PMID:41277498 | DOI:10.1002/jmri.70183

J Clin Psychol. 2025 Nov 24. doi: 10.1002/jclp.70069. Online ahead of print.

ABSTRACT

BACKGROUND: Depression and anxiety are increasingly common among children and adolescents. While school-based cognitive behavioral therapy (CBT) is a promising intervention, most research has focused on its effects in high-risk or symptomatic populations. This leaves a critical gap in our understanding of its effectiveness as a universal prevention strategy for the general, low-risk student population. Establishing whether CBT can benefit low-risk students is crucial for developing proactive, school-wide mental health systems aimed at preventing future problems before they emerge. This study aimed to fill this gap by evaluating the short- and long-term effects of universal school-based CBT on low-risk children and young people, providing insights for optimizing intervention programs.

METHODS: Systematic searches of MEDLINE, Embase, the Cochrane Library, Web of Science, and PsyInfo were conducted from inception to January 15, 2025 to identify randomized controlled trials (RCTs) of school-based CBT for depression and anxiety in low-risk populations. Paired and regression meta-analyses of these results were conducted using Bayesian hierarchical models.

RESULTS: The 31 RCTs included a total of 19,865 children and young people. Compared to the control group, school-based CBT produced a statistically significant but very small improvement in depressive symptoms (SMD: -0.06, 95% CrI: -0.08 to -0.04) and a small reduction in anxiety symptoms (SMD: -0.19, 95% CrI: -0.22 to -0.17). These effects appeared to be maintained for up to 1 year. Exploratory analyses suggested that males may benefit more from anxiety interventions.

CONCLUSION: This study provides the first meta-analytic evidence that universal school-based CBT can produce small but durable, long-term preventive effects in low-risk youth. Although the very low quality of the underlying evidence means the findings are not robust enough to support widespread implementation at this time, they establish a crucial signal of effectiveness. The primary implication is that universal CBT is a promising strategy that warrants significant investment in future high-quality, large-scale trials to confirm its real-world value.

PMID:41277494 | DOI:10.1002/jclp.70069

J Am Geriatr Soc. 2025 Nov 24. doi: 10.1111/jgs.70210. Online ahead of print.

ABSTRACT

BACKGROUND: Recent payment reforms in the United States have been credited with reducing the use of institutional post-acute care (PAC) after total knee arthroplasty (TKA) and total hip arthroplasty (THA). This dual-country study of Canada and the United States compares longitudinal trends in discharge to institutional PAC after primary TKA or THA.

METHODS: We conducted serial cross-sectional analyses to compare discharge to institutional PAC trends among adults aged ≥ 66 years undergoing primary TKA or THA in the United States and Canada from 2013 to 2019. Patient-level data were obtained from population-based Medicare claims in the United States and analogous datasets in Ontario. Discharge trends were assessed using standardized differences and linear regression models to evaluate relative changes over time.

RESULTS: Patients receiving TKA (2,308,001) and THA (1,234,149) in the United States and Ontario (106,721 and 53,371, respectively) were similar in age (73-74 years) and sex (~60% female). The absolute reduction in institutional PAC discharge over time for TKA was greater in the United States (slope = -3.59) than in Canada (slope = -0.53) (p < 0.0001), but relative reductions (slope = -8.78 in the United States, slope = -6.99 in Canada) were statistically similar (p = 0.08). THA showed a similar trend of absolute reductions; however, the relative reduction trend in the United States (slope = -9.98) was steeper than in Canada (slope = -6.46) (p = 0.0009).

CONCLUSIONS: The US payment reforms from 2013 to 2019 were associated with a greater impact on reducing institutional PAC utilization for THA than for TKA.

PMID:41277482 | DOI:10.1111/jgs.70210

Clin Endocrinol (Oxf). 2025 Nov 24. doi: 10.1111/cen.70062. Online ahead of print.

ABSTRACT

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common condition, that manifests as menstrual irregularities, subfertility, or symptoms of hyperandrogenism – including hirsutism, adult acne, and alopecia. Current pharmacological treatment of the hyperandrogenic symptoms includes the combined oral contraceptive pill. However, there are multiple contraindications and side-effects, which limit their use. Anti-androgens, such as spironolactone, are commonly prescribed off-label but its efficacy in PCOS is uncertain. This review aims to evaluate the efficacy and safety of spironolactone, when compared to other nonhormonal medications in the management of PCOS hyperandrogenic symptoms.

METHODS: Comprehensive literature searches were conducted across MEDLINE, EMBASES, PUBMED and SCOPUS. RCTs published in English assessing the use of spironolactone for hyperandrogenism in PCOS were included. The quality of papers was assessed using Cochrane RoB 2.0 tool. Meta-analysis was conducted using a random-effects model, reporting as standardised mean differences and 95% confidence intervals.

RESULTS: Of 3378 studies identified, five open-label RCTs met the inclusion criteria, three of which were included in the meta-analysis. Spironolactone, monotherapy or combination with metformin, showed no statistically significant difference in reducing Ferriman-Gallwey scores, total testosterone levels or BMI compared to metformin monotherapy. Side effects of spironolactone included menstrual irregularities, polyuria, and gastrointestinal symptoms.

CONCLUSION: Current evidence does not show any significant difference in the use of spironolactone when compared to metformin. Given its widespread use and limited safety concerns, spironolactone remains an off-label option, especially for those unable to take hormonal contraceptives. However, larger, better quality studies are needed to establish its efficacy in PCOS management.

PMID:41277478 | DOI:10.1111/cen.70062

Nutr Diet. 2025 Nov 24. doi: 10.1111/1747-0080.70058. Online ahead of print.

ABSTRACT

AIM: Caring for people with higher weight and complex health needs is increasingly common in hospitals. This study aimed to explore and compare inpatient and staff perspectives on the care of people with higher weight.

METHODS: Cross-sectional study using purpose-designed surveys within Metropolitan Victoria, Australia. Inpatients (who weighed over 100 kg) and hospital staff who provide care across four hospitals were invited to complete an inpatient-specific or staff-specific survey, respectively. Surveys contained questions related to clinical care, environment and dignity/respect. Data was analysed using descriptive statistics of scale-based items, and textual synthesis of free-text responses.

RESULTS: Thirty inpatients and 59 staff participated. Most inpatients reported their clinical care needs were met (73%-83%) and described appropriate equipment and staff support. However, 25% felt judged or emotionally unsupported, with some experiencing delays in care due to staffing or equipment availability. Staff were less positive, with 73% reporting difficulty accessing equipment, 71% citing inadequate staffing and only 39% agreeing that non-stigmatising care was provided. Differences in weight-related terminology preferences emerged: inpatients favoured the terms ‘higher weight’ (27%) or ‘obese/overweight’ (34%), while staff preferred ‘bariatric’ (71%). Three themes were identified: (1) Inappropriate equipment, delays to equipment-access can negatively impact on inpatient experience of care; (2) Processes of care and communication influence inpatient experience of care; and (3) Weight-related stigma.

CONCLUSIONS: Addressing gaps in care requires improved training, better resource access and alignment of language with consumer preferences to reduce stigma and deliver person-centred care.

PMID:41277470 | DOI:10.1111/1747-0080.70058