Category: Statistics

Glia. 2025 Mar 22. doi: 10.1002/glia.70019. Online ahead of print.

ABSTRACT

Individual protoplasmic astrocytes have very complex and diverse spongiform shapes. The morphological diversity of astrocytes is determined by the structural and functional interactions of the astrocyte with its microenvironment. When faced with pathological conditions, astrocytes reorganize their morphology. Yet, little is known about the astrocytic response in pure tauopathies and its evolution over time. Here, we aimed to investigate the consequences of a primary neuronal tau pathology on astrocyte fine morphology at three stages of the disease using the transgenic Thy-Tau22 mouse model. We first showed that hippocampal astrocytes in Thy-Tau22 mice progressively accumulate hyperphosphorylated tau with age. We then developed a pipeline of analyses, including 3D reconstruction of hippocampal tdTomato-labeled astrocytes via a PHP.eB adeno-associated virus, confocal microscopy, Imaris software morphometric analysis, and an advanced statistical analysis. During normal aging, the complexity of astrocyte morphology peaked at adulthood, then declined. In contrast, in Thy-Tau22 mice, tauopathy was associated with a simpler initial morphology, followed by the appearance of a cluster of complex cells at the most advanced stage. Using principal component analysis and hierarchical clustering based on 10 morphological features, we were able to identify different astrocyte morphotypes whose relative proportion varies differently with age between WT and Thy-Tau22 mice. Interestingly, we revealed that a fraction of astrocytes with a complex morphology re-emerges late in tauopathy-affected animals. Our data highlight the concept of significant and reversible structural plasticity of astrocytes when faced with chronic pathological conditions.

PMID:40119587 | DOI:10.1002/glia.70019

Ann Clin Biochem. 2025 Mar 21:45632251332460. doi: 10.1177/00045632251332460. Online ahead of print.

ABSTRACT

Objectives Urinary organic acid analysis is crucial for diagnosing inherited metabolic disorders (IMDs). This study assesses the impact of an external quality assessment (EQA) scheme on standardizing urinary organic acid detection in China from 2019 to 2023. Methods This retrospective longitudinal study analyzed data from the NCCL-E-25 EQA scheme for urinary organic acid analysis using gas chromatography-mass spectrometry (GC-MS). Ten batches of EQA data over five years were included, focusing on eight key organic acid metabolites. Robust statistical methods were used to evaluate laboratory performance, including regional variations, sample preparation methods, and laboratory types. Results Participating laboratories increased from 43 in 2019 to 76 in 2023, with high participation rates (median 94.74%). All eight target compounds showed significant reductions in robust coefficient of variation (CV) over time. Regional performance disparities narrowed, converging by 2022-2023. Extraction preparation methods generally outperformed non-extraction methods. Newborn Screening Centers (NBSCs) demonstrated lower robust CVs compared to non-NBSCs. Conclusions The EQA scheme effectively improved and standardized laboratory testing quality nationwide, particularly benefiting central and western regions. The study highlights the importance of standardized protocols and continuous improvement in enhancing IMD diagnostic accuracy. Future efforts should focus on encouraging wider participation, especially from underrepresented regions, and integrating quantitative and diagnostic capability assessments to comprehensively evaluate laboratory performance.

PMID:40118810 | DOI:10.1177/00045632251332460

J Am Heart Assoc. 2025 Mar 21:e039192. doi: 10.1161/JAHA.124.039192. Online ahead of print.

ABSTRACT

BACKGROUND: Low-voltage areas in the left atrium predict atrial fibrillation recurrence after catheter ablation and are associated with adverse outcomes like death, heart failure, and stroke. Detecting low-voltage areas (LVAs) typically requires invasive procedures, highlighting the need for a simple, minimally invasive marker. Vasoactive intestinal peptide (VIP), a neuropeptide released during parasympathetic stimulation, affects electrophysiological remodeling in atrial fibrillation. We hypothesized that serum VIP could serve as a biomarker for detecting LVAs in these patients.

METHODS AND RESULTS: This prospective, cross-sectional study was conducted at Hokkaido University Hospital between August 2021 and September 2023. We included 108 patients with atrial fibrillation scheduled for catheter ablation. Blood samples were collected during ablation to measure VIP using an ELISA. Electroanatomical mapping identified LVAs, defined as regions with bipolar voltage ≤0.5 mV and occupying >5% of the left atrial surface. Statistical analyses evaluated the relationship between VIP and LVAs. Fifty-one patients (47%) had LVAs, with significantly higher serum VIP levels than those without (335.1 versus 247.7 pg/mL, P<0.001). VIP levels and female sex were statistically significant factors of LVAs. Adding VIP to the existing score significantly improved its discrimination (area under the curve: 0.784 versus 0.707, P<0.001).

CONCLUSIONS: Serum VIP levels are higher in patients with atrial fibrillation with LVAs, suggesting its potential as a noninvasive biomarker for detecting these areas and improving clinical management.

PMID:40118798 | DOI:10.1161/JAHA.124.039192

J Public Health Dent. 2025 Mar 21. doi: 10.1111/jphd.12670. Online ahead of print.

ABSTRACT

BACKGROUND: Oral Healthcare workers, including dental students, face a great risk of COVID-19 infection. High COVID-19 vaccination coverage is essential for a protected workforce. This study, which aims to document the COVID-19 vaccination experience among dental students and employees from Canadian dental schools during the COVID-19 pandemic, provides crucial insights that can significantly impact future vaccination strategies.

METHODS: This study used data from a prospective cohort conducted between April 2021 and May 2022. We recruited 600 participants, including dental students, faculty, and support staff from 10 Canadian dental schools. Data were collected monthly from all subjects. Vaccination acceptance and vaccination time were assessed. Logistic regression models were performed to identify predictors of COVID-19 vaccine acceptance and late vaccination. In order to detect hesitation tendencies, descriptive statistics were used to observe the distribution of time to vaccination between age groups of employees and students.

RESULTS: Out of 600 participants at baseline (70% female; average age 36 years old), 91% received at least one dose of the COVID-19 vaccine. No associations were found between sociodemographic factors and COVID-19 vaccine acceptance. Individuals aged 50-59 were less likely to delay the vaccination than most of our sample. Students presented more outliers for later vaccination times, particularly in younger age groups.

CONCLUSION: High vaccination acceptance among dental students is crucial for promoting professionalism and influencing patients. Integrating vaccine advocacy into their education might enhance vaccination uptake in the general population.

PMID:40118795 | DOI:10.1111/jphd.12670

J Am Heart Assoc. 2025 Mar 21:e036193. doi: 10.1161/JAHA.124.036193. Online ahead of print.

ABSTRACT

BACKGROUND: Essential hypertension (EH) is a global health issue. Despite extensive research, much of EH heritability remains unexplained. We investigated the genetic basis of EH in African-derived individuals from partially isolated quilombo populations in Vale do Ribeira (São Paulo, Brazil).

METHODS AND RESULTS: Samples from 431 individuals (167 affected, 261 unaffected, 3 unknown) were genotyped using a 650 000 single-nucleotide polymorphism array. Estimated global ancestry proportions were 47% African, 36% European, and 16% Native American. We constructed 6 pedigrees using additional data from 673 individuals and created 3 nonoverlapping single-nucleotide polymorphism subpanels. We phased haplotypes and performed local ancestry analysis to account for admixture. Genome-wide linkage analysis and fine-mapping via family-based association studies were conducted, prioritizing EH-associated genes through a systematic approach involving databases like PubMed, ClinVar, and GWAS (Genome-Wide Association Studies) Catalog. Linkage analysis identified 22 regions of interest with logarithm of the odds scores ranging from 1.45 to 3.03, encompassing 2363 genes. Fine-mapping (family-based association studies) identified 60 EH-related candidate genes and 117 suggestive/significant variants. Among these, 14 genes, including PHGDH, S100A10, MFN2, and RYR2, were strongly related to hypertension harboring 29 suggestive/significant single-nucleotide polymorphisms.

CONCLUSIONS: Through a complementary approach combining admixture-adjusted Genome-wide linkage analysis based on Markov chain Monte Carlo methods, family-based association studies on known and imputed data, and gene prioritizing, new loci, variants, and candidate genes were identified. These findings provide targets for future research, replication in other populations, facilitate personalized treatments, and improve public health toward African-derived underrepresented populations. Limitations include restricted single-nucleotide polymorphism coverage, self-reported pedigree data, and lack of available EH genomic studies on admixed populations for independent validation, despite the performed genetic correlation analyses using summary statistics.

PMID:40118787 | DOI:10.1161/JAHA.124.036193

Pediatr Neonatol. 2025 Mar 7:S1875-9572(25)00055-5. doi: 10.1016/j.pedneo.2024.03.014. Online ahead of print.

ABSTRACT

BACKGROUND: Considerable research has shown brain injury during surgery for patients with cyanotic congenital heart disease (CHD), but the preoperative neurodevelopment and brain injury in children with non-cyanotic CHD are not well understood. The aim of this study is to investigate changes in global and local grey matter (GM) volumes of pediatric patients with non-cyanotic CHD before catheter-based procedure using voxel-based morphometry (VBM).

METHODS: One-to three-year-old toddlers with acyanotic CHD (n = 54) hospitalized for treatment were prospectively enrolled. Each toddler underwent a 3D T1-weighted brain Magnetic Resonance Imaging (MRI) scan before catheter-based procedure. Meanwhile, 3D T1-weighted brain MR images of age- and sex-matched healthy controls (n = 35) were retrospectively analyzed. The volume of GM and total intracranial volume (TIV) were assessed by VBM within the SPM 12 (Statistical Parametric Mapping software), and regional differences in GM volume were analyzed by two-sample t-test and familywise error (FWE) rate correction.

RESULTS: There was no difference in gross GM volume and TIV between the two groups (p > 0.05), but VBM analysis showed reduced structures of GM in middle frontal gyrus (both sides), inferior frontal gyrus, orbital gyrus, subcallosal gyrus, thalamus (both sides), medial globus pallidus (both sides) and culmen (both sides) of the non-cyanotic CHD group compared with the controls (p < 0.05, FWE correction).

CONCLUSION: Toddlers aged 1-3 years with acyanotic CHD suffer a decrease in local GM volume before catheter-based procedure, which tends to be distributed across the bilateral frontal lobe, thalamus, globus pallidus, and cerebellum.

PMID:40118765 | DOI:10.1016/j.pedneo.2024.03.014

Prim Care Diabetes. 2025 Mar 20:S1751-9918(25)00079-8. doi: 10.1016/j.pcd.2025.03.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Social isolation and loneliness are forms of social disconnection that have been linked to increased risk of many metabolic disorders, including Type 2 Diabetes Mellitus (T2DM). However, evidence to support this relation is lacking. This study aims to investigate the association between social isolation, loneliness, and the incidence risk of T2DM.

METHODS: We searched various electronic databases including MEDLINE (via PubMed), Embase, the Cochrane Library, and Google scholar to retrieve qualitative studies comparing the incidence of T2DM in patients with social isolation or loneliness. We performed statistical analysis on RevMan 5.4 using the random effect model.

RESULTS: Loneliness was associated with a significantly increased incidence of T2DM (OR: 1.44; 95 % CI: 1.19-1.73; P:0.0001), with high heterogeneity (I² = 95 %). Sensitivity analysis indicated potential variability due to differences in loneliness measurements. Social isolation also showed a significant association with T2DM (OR: 1.88; 95 % CI: 1.38-2.58; P:<0.0001) with high heterogeneity (I² = 98 %).

CONCLUSION: In conclusion, we found social isolation and loneliness are independently associated with a higher incidence of T2DM. These findings underscore the need to address psychosocial elements like social isolation and loneliness in the management of T2DM. However, further studies with larger sample sizes, longer follow-up durations, and uniform criteria is warranted to better understand the association between social isolation, loneliness and T2DM.

PMID:40118745 | DOI:10.1016/j.pcd.2025.03.006

J Cardiothorac Vasc Anesth. 2025 Feb 28:S1053-0770(25)00193-4. doi: 10.1053/j.jvca.2025.02.048. Online ahead of print.

ABSTRACT

OBJECTIVE: Hemolysis is a complication in surgical procedures requiring cardiopulmonary bypass (CPB). The primary aim of this study was to evaluate the effectiveness of the point-of-care device Hemcheck Helge V-Test, quantifying hemolysis during cardiac surgery with CPB.

DESIGN: Prospective-observational study.

SETTING: Single-center study.

PARTICIPANTS: Patients undergoing elective cardiac surgery with CPB.

INTERVENTIONS: Blood samples of 78 patients were simultaneously collected during surgery at T0: pre-CPB; T1: at aorta clamping; T2: at 20 minutes after the CPB start; T3: at the end of CPB; and T4: at the end of surgery. Samples were analyzed by the Hemcheck Helge V-Test device, which offers a real-time assessment of hemolysis through the value of plasma-free hemoglobin (PfHb) expressed in mg/dL.

MEASUREMENTS AND MAIN RESULTS: No case of hemolysis (PfHb ≥50 mg/dL) was recorded at T0. The results recorded median PfHb values at T0 = 0.5 (0-7.1) mg/dL, T1 = 3.75 (0-14.4) mg/dL; T2 = 8.25 (0.4-19.1) mg/dL, T3 = 27.5 (9.9-50) mg/dL, and T4 = 18.5 (2.4-41) mg/dL; for all T times, p-values were < 0.001. A statistically significant correlation was recorded between hemolysis values >50 mg/dL at T3 and CPB time >100 minutes (p < 0.05).

CONCLUSIONS: The use of Hemcheck Helge V-Test allows effective identification of hemolysis directly in the operating room, reducing wasted time for laboratory analyses. This could help the anesthesiologist, perfusionist, or cardiac surgeon address intraoperative hemolysis and its effects on organ function earlier and improve the postoperative course of patients undergoing cardiac surgery with CPB.

PMID:40118733 | DOI:10.1053/j.jvca.2025.02.048

J Prev Alzheimers Dis. 2025 Mar 20:100133. doi: 10.1016/j.tjpad.2025.100133. Online ahead of print.

ABSTRACT

INTRODUCTION: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

METHODS: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change).

RESULTS: Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95 %CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80 % power (5 % statistical significance) to detect a 25 % reduction in absolute levels of pathology, allowing 40 % dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50 % reduction in rate of change. Sample sizes ranged from 250 to 900 (examples hippocampal volume: 338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG and cognitive outcomes had lower sample sizes when including indivduals with mild impairment (CDR=0.5 and 1) as well as presymptomatic individuals (CDR=0).

DISCUSSION: Despite the rarity of ADAD, presymptomatic clinical trials with feasible sample sizes given the number of cases appear possible.

PMID:40118731 | DOI:10.1016/j.tjpad.2025.100133

Sleep Health. 2025 Mar 20:S2352-7218(25)00032-4. doi: 10.1016/j.sleh.2025.01.012. Online ahead of print.

ABSTRACT

OBJECTIVES: Model-based clustering is increasingly used to identify multidimensional sleep health profiles. However, generalizability is rarely assessed because of complexities of data sharing and harmonization. Our goal was to evaluate the generalizability of multidimensional sleep health profiles across older adult populations in Western countries and assess whether they predict depressive symptoms over time.

METHODS: We harmonized five self-reported sleep health indicators (satisfaction, alertness, timing, efficiency, and duration) across six population-based cohorts from the United States and Netherlands (N=614 – 3209 each) and performed identical latent class analysis in each cohort. Novel multivariable similarity metrics, patterns of sleep health and cluster sizes were used to match clusters and assess generalizability across cohorts. We compared cluster characteristics cross-sectionally and used linear mixed-effects modeling to relate sleep health clusters to depressive symptoms over time.

RESULTS: “Average sleep health” (moderate duration; high quality/efficiency; 42.7%-76.7% of sample) and “poor sleep health” (short duration; low quality/efficiency; high daytime sleepiness; 9.4%-20.4% of sample) clusters were generalizable across cohorts. In four cohorts “inefficient sleep” clusters were identified and in two cohorts “long, efficient sleep” clusters were identified. At 3years, those in the poor sleep cluster had depression symptoms that were 1.40-2.79 times greater than in the average sleep cluster, across all cohorts.

CONCLUSIONS: We identified two profiles – average sleep health and poor sleep health – that were generalizable across six samples of older adults and predicted depressive symptoms, underscoring the importance of the sleep health paradigm.

PMID:40118730 | DOI:10.1016/j.sleh.2025.01.012