Category: Statistics

Front Hum Neurosci. 2025 Oct 28;19:1652773. doi: 10.3389/fnhum.2025.1652773. eCollection 2025.

ABSTRACT

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to nonspecific initial symptoms. Although electroencephalography (EEG) is a key diagnostic tool, particularly through the detection of periodic sharp wave complexes (PSWCs), the longitudinal evolution of EEG features and their correlation with clinical and neuroimaging progression are not fully characterized.

METHODS: This retrospective cohort study analyzed 37 patients diagnosed with probable and very probable sCJD according to the 2021 Chinese diagnostic guidelines. All patients underwent at least one EEG examination. One representative patient was followed for 23 weeks with serial EEG and MRI studies to document dynamic electrophysiological and structural changes. EEG background activity was graded as mild, moderate, or severe, and PSWCs were identified based on standardized criteria. MRI analyses focused on the spatial and temporal progression of hyperintense lesions on DWI and FLAIR sequences.

RESULTS: Among the 37 patients, 46% underwent initial EEG within 1 month of symptom onset, and 49% exhibited severe background abnormalities. PSWCs were present in 84% of patients at first EEG, with a high prevalence (82%) even in those examined within 4 weeks of onset. Longitudinal analysis in the index case revealed a progressive EEG deterioration: from slowed and disorganized background rhythms and emerging triphasic waves at 8 weeks, to widespread PSWCs with increasing periodicity (9-16 weeks), and finally to a burst-suppression pattern near electrical silence by week 23. Concurrent MRI showed a parallel expansion of hyperintense lesions from unilateral cortical and basal ganglia regions to bilateral involvement, closely correlated with the EEG progression. Statistical analysis showed no significant correlation between survival time and age, time to first EEG, CSF 14-3-3 protein status, or initial EEG background grade. Furthermore, neither the presence of typical PSWCs nor the severity of background activity was associated with survival outcomes.

CONCLUSION: EEG, especially the early and highly prevalent presence of PSWCs, offers high diagnostic value in sCJD but does not serve as prognostic predictors. The close correlation between EEG decline and MRI progression supports multimodal monitoring. Serial EEG should be integrated into sCJD diagnosis and follow-up.

PMID:41230545 | PMC:PMC12602467 | DOI:10.3389/fnhum.2025.1652773

J R Stat Soc Series B Stat Methodol. 2025 May 27;87(5):1508-1527. doi: 10.1093/jrsssb/qkaf028. eCollection 2025 Nov.

ABSTRACT

When an exposure of interest is confounded by unmeasured factors, an instrumental variable (IV) can be used to identify and estimate certain causal contrasts. Identification of the marginal average treatment effect (ATE) from IVs relies on strong untestable structural assumptions. When one is unwilling to assert such structure, IVs can nonetheless be used to construct bounds on the ATE. Famously, Alexander Balke and Judea Pearl proved tight bounds on the ATE for a binary outcome, in a randomized trial with noncompliance and no covariate information. We demonstrate how these bounds remain useful in observational settings with baseline confounders of the IV, as well as randomized trials with measured baseline covariates. The resulting bounds on the ATE are nonsmooth functionals, and thus standard nonparametric efficiency theory is not immediately applicable. To remedy this, we propose (1) under a novel margin condition, influence function-based estimators of the bounds that can attain parametric convergence rates when the nuisance functions are modelled flexibly, and (2) estimators of smooth approximations of these bounds. We propose extensions to continuous outcomes, explore finite sample properties in simulations, and illustrate the proposed estimators in an observational study targeting the effect of higher education on wages.

PMID:41230541 | PMC:PMC12602419 | DOI:10.1093/jrsssb/qkaf028

Front Neurosci. 2025 Oct 28;19:1638503. doi: 10.3389/fnins.2025.1638503. eCollection 2025.

ABSTRACT

INTRODUCTION: Alzheimer’s disease involves progressive white matter microstructural degeneration that may precede clinical symptoms by decades. While polygenic risk scores (PRS) quantify cumulative genetic liability for AD, genome-wide PRS lack mechanistic specificity. We tested whether pathway-specific PRS, targeting areas of biology including tau binding, lipid metabolism, and immune response, are differentially associated with diffusion MRI measures across the lifespan.

METHODS: We analyzed two population-based cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC; mean age = 19.8 years, n = 517) and UK Biobank (mean age = 64.2 years, n = 18,172). Genome-wide and nine pathway-specific PRS for Alzheimer’s disease were constructed using GWAS summary statistics and a clumping threshold of r² < 0.2 at p < 0.001. Diffusion MRI data were processed separately within each cohort: in ALSPAC, tract-based fractional anisotropy (FA) and mean diffusivity (MD) were extracted using probabilistic tractography from native-space regions of interest; in UK Biobank, diffusion metrics were derived from TBSS-aligned skeletons and standard atlas-based ROIs. Analyses focused on three tracts vulnerable to early AD pathology: the dorsal cingulum, parahippocampal cingulum, and fornix. Multiple linear regression models were used to assess PRS associations with FA and MD, adjusting for demographic, scanner, and genetic ancestry covariates. False discovery rate correction addressed multiple comparisons, and sensitivity analyses were performed excluding the APOE region.

RESULTS: In UK Biobank, higher PRS for protein-lipid complex assembly and tau protein binding were robustly associated with lower fractional anisotropy and higher mean diffusivity in both dorsal and parahippocampal cingulum segments (False discovery rate-corrected p < 0.05), explaining more variance than APOE alone; no significant effects emerged in the fornix. Genome-wide PRS showed weaker, non-significant associations. In ALSPAC, no PRS metric survived FDR correction, though nominal trends appeared in the dorsal cingulum. Sensitivity analyses confirmed that key cingulum associations in older adults persisted after omitting APOE.

CONCLUSION: Pathway-specific polygenic risk for Alzheimer’s disease manifests in white matter microstructure by mid- to late adulthood but not in early adulthood, suggesting an age-dependent emergence of genetic effects. dMRI phenotypes may thus serve as intermediate biomarkers for dissecting mechanistic pathways of preclinical Alzheimer’s disease vulnerability.

PMID:41230509 | PMC:PMC12602405 | DOI:10.3389/fnins.2025.1638503

Bioinform Adv. 2025 Nov 4;5(1):vbaf255. doi: 10.1093/bioadv/vbaf255. eCollection 2025.

ABSTRACT

SUMMARY: To enable flexible, scalable, and reproducible microbiota profiling, we have developed zAMP, an open-source bioinformatics pipeline for the analysis of amplicon sequence data, such as 16S rRNA gene for bacteria and archaea or ITS for fungi. zAMP is complemented by two modules: one to process databases to optimize taxonomy assignment, and the second to benchmark primers, databases and classifier performances. Coupled with zAMPExplorer, an interactive R Shiny application that provides an intuitive interface for quality control, diversity analysis, and statistical testing, this complete toolbox addresses both research and clinical needs in microbiota profiling.

AVAILABILITY AND IMPLEMENTATION: Comprehensive documentation and tutorials are provided alongside the source code of zAMP and zAMPExplorer software to facilitate installation and use. zAMP is implemented as a Snakemake workflow, ensuring reproducibility by running within Singularity or Docker containers, and is also easily installable via Bioconda. The zAMPExplorer application, designed for visualization and statistical analysis, can be installed using either a Docker image or from R-universe.

PMID:41230489 | PMC:PMC12603355 | DOI:10.1093/bioadv/vbaf255

Cureus. 2025 Nov 10;17(11):e96486. doi: 10.7759/cureus.96486. eCollection 2025 Nov.

ABSTRACT

INTRODUCTION: Perforation of a duodenal ulcer is a severe complication of peptic ulcer disease that requires prompt resuscitation and appropriate surgical intervention to minimize morbidity and mortality. This study aimed to compare the outcomes and complications of Graham’s patch versus modified Graham’s patch repair in patients with perforated duodenal ulcers admitted to a tertiary care hospital in Bangladesh.

METHODS: This comparative observational study was conducted in the Department of Surgery at Dhaka Medical College Hospital (DMCH) in Dhaka, Bangladesh, over a six-month period in 2018. Patients diagnosed with duodenal ulcer perforation were selected based on pre-defined inclusion criteria. Informed written consent was obtained from all participants prior to enrollment. A total of 60 patients (30 in each group) were included using a systematic sampling method. Data on post-operative outcomes and complications, such as leakage and wound infection, were collected using a pre-designed data sheet. Data analysis was performed using IBM SPSS Statistics for Windows, V. 24.0 (IBM Corp., Armonk, NY, USA).

RESULTS: The study included 60 participants with a mean age of 34.22±8.59 years (range: 16-53 years) and a male-to-female ratio of 2:1. In the Graham’s patch group, 90% of patients had pus in the intraperitoneal cavity, compared to 67% in the modified Graham’s patch group. Wound infection and post-operative fever were the most common complications observed in both groups, with no statistically significant differences (p=0.59; p=0.78). The average hospital stay was six days for the Graham’s patch group and eight days for the modified Graham’s patch group, also showing no significant difference between the groups (p=0.145).

CONCLUSION: This study compared the short-term outcomes of traditional versus modified Graham’s patch repairs for perforated duodenal ulcers and found no significant differences in post-operative complications or hospital stay. Both techniques were safe and effective, allowing surgeons to choose based on experience and intra-operative factors, with the modified patch potentially offering easier handling for certain cases. However, due to limitations like small sample size and short follow-up, larger multi-center trials are needed to better assess long-term outcomes and guide surgical practice.

PMID:41230479 | PMC:PMC12603592 | DOI:10.7759/cureus.96486

Cureus. 2025 Nov 10;17(11):e96494. doi: 10.7759/cureus.96494. eCollection 2025 Nov.

ABSTRACT

Introduction Seroma formation is a frequent complication after simple mastectomy due to the creation of a large dead space. Multiple aspirations are required to manage patients’ symptoms. At present, breast surgeons lack consensus on effective preventative strategies. To address this issue, we have implemented a technique called quilting, which involves suturing the mastectomy flap to the chest wall muscle to convert the dead space into smaller compartments, thereby reducing the possibility of seroma. Method An audit was carried out from April 2020 to June 2021 to establish postoperative seroma rates for patients undergoing simple mastectomy without reconstruction. A subsequent evaluation was completed between October 2023 and December 2024 following the adoption of quilting as standard practice. After each stage, results were shared with UK breast surgeons along with a survey to assess perceptions of quilting and other preventive strategies. An analysis was then done to examine the relationship between sharing audit data and the decision to quilt. This study seeks to outline the effectiveness of quilting in the prevention of seroma formation while also assessing current and alternative practices of UK surgeons in managing seromas. The insights gained from the quilting audit were shared in a follow-up survey to challenge the perception surgeons held of quilting and to consider incorporating this technique into their future practices. Results A total of 66 simple mastectomies were performed, with 32 patients receiving quilting and 34 undergoing conventional closure. On average, each patient in the quilting group received 13 sutures, taking an average of nine minutes for suturing. Among the 32 patients in the quilting group, there were no failed day cases due to postoperative haematomas or complications such as pain, wound breakdown, or long-term disfigurement of the flap. Only one case developed a seroma, but the volume was not clinically significant enough to require drainage. The non-quilting group showed a 70% seroma rate, with patients averaging three aspirations each, averaging 230 ml of fluid. Sixty UK-based surgeons responded to the first survey and 48 to the second. The first survey revealed that only 11.6% of surgeons offered quilting, 48% relied on drains, and 35% took no measures to prevent seroma formation. After sharing the quilting audit results, 79% of respondents indicated they would consider implementing quilting, while 20% remained resistant to the idea. The changes to response were statistically significant (p<0.00001). Conclusion The feedback from the surveys indicates a lack of consensus among UK surgeons regarding the prevention of seromas post-mastectomy. Nonetheless, there is a significant willingness to explore quilting. Our findings demonstrate that quilting is both safe and effective in reducing seroma formation, leading to improved patient outcomes. We recommend that future research focus on establishing comprehensive national evidence and guidelines aimed at decreasing seroma rates, thus addressing the current variability in approach across the country.

PMID:41230474 | PMC:PMC12603609 | DOI:10.7759/cureus.96494

OTO Open. 2025 Nov 10;9(4):e70181. doi: 10.1002/oto2.70181. eCollection 2025 Oct-Dec.

ABSTRACT

OBJECTIVE: To evaluate the validity of the Oura Ring (OR; Oura Health Ltd.) in measuring sleep parameters compared to medical-grade sleep studies including polysomnography (PSG) or actigraphy (ACT).

DATA SOURCES: PubMed, Scopus, and CINAHL.

REVIEW METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Studies were included if they evaluated sleep parameters measured simultaneously by the OR and PSG or ACT. Outcomes assessed included Total Sleep Time (TST), Sleep Efficiency (SE), Wake After Sleep Onset (WASO), Sleep Onset Latency (SOL), Light Sleep Time (LST), Deep Sleep Time (DST), and Rapid Eye Movement (REM) sleep time. Mean differences with 95% confidence intervals were calculated using a random-effects model. A P < .05 was considered statistically significant.

RESULTS: Out of 2104 articles, 6 studies (n = 388) were included. There were no statistically significant differences between the OR and PSG/ACT for TST (MD: -2.97 min; 95% confidence interval [CI]: -10.27 to 4.33), SE (MD: -1.32%; 95% CI: -2.76 to 0.12), WASO (MD: 1.64 min; 95% CI: -12.57 to 15.86), SOL (MD: 0.48 min; 95% CI: -2.93 to 3.89), LST (MD: -4.27 min; 95% CI: -24.68 to 16.13), DST (MD: 1.39 min; 95% CI: -10.45 to 13.23), and REM sleep time (MD: -3.89 min; 95% CI: -17.23 to 9.46).

CONCLUSION: The OR demonstrates comparable accuracy to PSG and ACT for commonly measured sleep parameters, supporting its utility as a self-monitoring tool. This could prompt earlier clinical evaluation in symptomatic individuals or support remote monitoring of sleep.

PMID:41230431 | PMC:PMC12602993 | DOI:10.1002/oto2.70181

Appl Bionics Biomech. 2025 Nov 10;2025:5951085. doi: 10.1155/abb/5951085. eCollection 2025.

ABSTRACT

Knee motion involves intricate coordination among various anatomical structures. Effective treatment of knee pathologies requires precise identification of deformities and accurate surgical interventions, which often involve rapid tissue modification based on established knowledge. However, motion disorders are typically detected long after surgery. To address this, a simulation environment is proposed to plan and analyze surgical impacts on knee motion. Comprehensive knee joint modeling is crucial for a successful simulation. Clinically accepted movement procedures based on passive knee motion make tibiofemoral articulation modeling sufficient. Proposed model tibiofemoral articulation, incorporating 15 ligaments, tibial and femoral bones, and cartilages. Ligaments’ tensile, bones’, and cartilages’ contact forces (CFs) define internal force interactions. Anatomical structures, their shapes, positions, and attachment points are identified from MRI, ensuring patient-specific modeling. Simulation results are compared to cadaver data using passive knee motion. Two rotational and three translational dependent joint motions (JMs) are compared pairwise. The results are highly correlated with the clinical benchmark. Pearson’s correlation show a strong association between experimental and simulated passive knee flexions (PKFs; r > 0.89). The comparison is statistically significant with p < 0.05. Anterior-posterior translation showed the highest correlation (R ² = 0.994). The findings indicate that the simulated model closely replicates actual knee responses.

PMID:41230427 | PMC:PMC12602475 | DOI:10.1155/abb/5951085

Orthop J Sports Med. 2025 Nov 7;13(11):23259671251386445. doi: 10.1177/23259671251386445. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: Anterior cruciate ligament (ACL) tears can be a source of significant morbidity, with the potential for career-altering implications for athletes who sustain them. Specific knee biomechanics during a drop vertical jump have been shown to be associated with an increased risk for ACL injury in collegiate varsity athletes. Presently, the evolution of these kinematics from preseason to postseason is not well-understood.

PURPOSE: To compare preseason and postseason knee biomechanics during a drop vertical jump in collegiate varsity athletes and identify changes in ACL injury risk.

STUDY DESIGN: Cohort study; Level of evidence, 2.

METHODS: A total of 114 collegiate athletes were prospectively enrolled. Of these 114, 67 athletes (male, 21 [31%]; female, 46 [69%]) completed properly captured preseason and postseason drop vertical jumps tracked by an affordable motion capture system. Initial coronal (IC), peak coronal (PC), and peak sagittal (PS) angles of the knee were compared between preseason and postseason using the Wilcoxon signed-rank test and paired-samples t test. Athletes at high risk for ACL injury were identified based on published cutoff angles: IC angle >2.96°, PC angle >6.16°, and PS angle <93.82°, then the distribution of these athletes was compared.

RESULTS: In male athletes, all preseason knee angles were in the low-risk range. At postseason, men presented a nonsignificant reduction in mean IC and PC knee angles and a nonsignificant reduction in mean PS angle (90.88 ± 10.69). On average, female athletes were at high risk at preseason according to mean IC and PS angles (4.24 ± 1.09 and 92.90 ± 6.94, respectively). There was a statistically significant reduction in mean IC angle (mean difference [MD], 2.23; P = .03) and mean PC angle (MD, 0.76; P = .04); however, mean IC angle remained in the high-risk range. There was a nonsignificant reduction in mean PS angle, which remained within the high-risk range (MD, 3.96; P = .24).

CONCLUSION: Our study demonstrated that female collegiate varsity athletes demonstrate higher risk knee biomechanics in comparison with their male counterparts. Even with improved biomechanics as their season advances, female athletes have a persistently low PS angle, leaving them at high risk of ACL injury. Using a portable and reliable motion capture system may facilitate monitoring knee kinematics, which could translate into a tool for ACL injury prevention in athletes.

PMID:41230424 | PMC:PMC12602941 | DOI:10.1177/23259671251386445

Orthop J Sports Med. 2025 Nov 10;13(11):23259671251389142. doi: 10.1177/23259671251389142. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: Scheduled follow-up (FU) appointments are a vital element of monitoring patient progress and outcomes. However, failure to attend FU appointments continues to be a regular problem in orthopaedics.

PURPOSE: To investigate the relationship between FU appointment attendance and functional outcomes after hip arthroscopy.

STUDY DESIGN: Cohort Study; Level of evidence, 3.

METHODS: A retrospective analysis of prospectively collected data was conducted in patients who underwent primary hip arthroscopy for symptomatic labral tears between 2014 and 2023. FU attendance after suture removal was used to categorize patients into 2 cohorts based on whether they attended all standard FU appointments (AA) or missed at least 1 FU appointment (MAO) at 3-, 6-, or 12-month intervals. Patient-reported outcome measures (PROMs) included the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Activities of Daily Living, HOS-Sports Specific Subscale, 33-item International Hip Outcome Tool, and patient satisfaction.

RESULTS: Overall, 178 hips (54.5% women) met the inclusion criteria, with 110 hips (mean age, 35.9 ± 10.6 years) in the AA cohort and 68 hips (mean age, 35.1 ± 11.8 years) in the MAO cohort. Both groups had similar radiographic and demographic characteristics, except for the distribution of Asian and White patients (18 vs 3 and 44 vs 100, respectively; P < .001). PROMs were statistically similar at all time points (P > .05). Multivariate linear regression model analyses showed no differences after adjusting for cohort, distance from clinic, sex, race, and age for all PROMs. Additionally, both cohorts achieved clinically meaningful outcomes (CMOs) at similar rates (P > .05).

CONCLUSION: Patients who missed at least 1 FU appointment achieved similar improvements in functional outcomes compared with those who attended all. Both cohorts achieved minimal clinically important difference, patient acceptable symptom score, and significant clinical benefit at comparably high rates. These findings suggest that functional outcomes are not associated with FU appointment attendance. Additionally, those who do not attend all of their postoperative FU appointments can still achieve CMOs.

PMID:41230422 | PMC:PMC12603001 | DOI:10.1177/23259671251389142