Category: Statistics

bioRxiv [Preprint]. 2024 Oct 23:2024.10.23.619767. doi: 10.1101/2024.10.23.619767.

ABSTRACT

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets – containing association data for all variants in the analysis – are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

PMID:39484403 | PMC:PMC11526975 | DOI:10.1101/2024.10.23.619767

bioRxiv [Preprint]. 2024 Oct 22:2024.10.19.619237. doi: 10.1101/2024.10.19.619237.

ABSTRACT

The structural connections of the brain’s white matter are critical for brain function. Diffusion MRI tractography enables the in-vivo reconstruction of white matter fiber bundles and the study of their relationship to covariates of interest, such as neurobehavioral or clinical factors. In this work, we introduce Fiber Microstructure Quantile (FMQ) Regression, a new statistical approach for studying the association between white matter fiber bundles and scalar factors (e.g., cognitive scores). Our approach analyzes tissue microstructure measures based on quantile-specific bundle regions . These regions are defined according to the quantiles of fractional anisotropy (FA) from the periphery to the core of a population fiber bundle, which pools all individuals’ bundles. To investigate how fiber bundle tissue microstructure relates to covariates of interest, we employ the statistical technique of quantile regression. Unlike ordinary regression, which only models a conditional mean, quantile regression models the conditional quantiles of a response variable. This enables the proposed analysis, where a quantile regression is fitted for each quantile-specific bundle region. To demonstrate FMQ Regression, we perform an illustrative study in a large healthy young adult tractography dataset derived from the Human Connectome Project-Young Adult (HCP-YA), focusing on particular bundles expected to relate to particular aspects of cognition and motor function. Importantly, our analysis considers sex-specific effects in brain-behavior associations. In comparison with a traditional method, Automated Fiber Quantification (AFQ), which enables FA analysis in regions defined along the trajectory of a bundle, our results suggest that FMQ Regression is much more powerful for detecting brain-behavior associations. Importantly, FMQ Regression finds significant brain-behavior associations in multiple bundles, including findings unique to males or to females. In both males and females, language performance is significantly associated with FA in the left arcuate fasciculus, with stronger associations in the bundle’s periphery. In males only, memory performance is significantly associated with FA in the left uncinate fasciculus, particularly in intermediate regions of the bundle. In females only, motor performance is significantly associated with FA in the left and right corticospinal tracts, with a slightly lower relationship at the bundle periphery and a slightly higher relationship toward the bundle core. No significant relationships are found between executive function and cingulum bundle FA. Our study demonstrates that FMQ Regression is a powerful statistical approach that can provide insight into associations from bundle periphery to bundle core. Our results also identify several brain-behavior relationships unique to males or to females, highlighting the importance of considering sex differences in future research.

PMID:39484397 | PMC:PMC11526951 | DOI:10.1101/2024.10.19.619237

bioRxiv [Preprint]. 2024 Oct 21:2024.10.17.618945. doi: 10.1101/2024.10.17.618945.

ABSTRACT

Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline BRCA1 and BRCA2 (gBRCA1/2) carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors. gBRCA1/2 -driven hereditary and sporadic tumors undergo convergent evolution to develop a similar set of driver deletions, and deletions explain the elevated cancer risk of gBRCA1/2 -carriers. Orthogonal mutation timing analysis identifies deletions of chromosome 17 and 13q as early, recurrent events. Single-cell analyses confirmed deletion rate differences in gBRCA1/2 vs. non-carrier tumors as well as cells engineered to harbor gBRCA1/2 . The centrality of deletion-associated chromosomal instability to tumorigenesis shapes interpretation of the somatic evolution of non-malignant tissue and guides strategies for precision prevention and early detection.

PMID:39484366 | PMC:PMC11526986 | DOI:10.1101/2024.10.17.618945

Front Aging Neurosci. 2024 Oct 17;16:1406573. doi: 10.3389/fnagi.2024.1406573. eCollection 2024.

ABSTRACT

BACKGROUND AND AIMS: The relationship between the ABCA7 gene and Alzheimer’s disease (AD) has been widely studied across various populations. However, the results have been inconsistent. This meta-analysis aimed to evaluate the association of ABCA7 polymorphisms with AD risk, including specific subtypes such as late-onset Alzheimer’s disease (LOAD).

METHODS: Relevant studies were identified through comprehensive database searches, and the quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). Allele and genotype frequencies were extracted from the included studies. The pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models. Multiple testing corrections were conducted using the false discovery rate (FDR) method. The Cochran Q statistic and I² metric were used to evaluate heterogeneity between studies, while Egger’s test and funnel plots were employed to assess publication bias.

RESULTS: A total of 36 studies, covering 21 polymorphisms and involving 31,809 AD cases and 44,994 controls, were included in this meta-analysis. NOS scores ranged from 7 to 9, indicating high-quality studies. A total of 11 SNPs (rs3764650, rs3752246, rs4147929, rs3752232, rs3752243, rs3764645, rs4147934, rs200538373, rs4147914, rs4147915, and rs115550680) in ABCA7 were significantly associated with AD risk. Among these SNPs, two (rs3764650 and rs3752246) were also found to be related to the late-onset AD (LOAD) subtype. In addition, two SNPs (rs4147929 and rs4147934) were associated with the susceptibility to AD only in non-Hispanic White populations. A total of 10 SNPs (rs3764647, rs3752229, rs3752237, rs4147932, rs113809142, rs3745842, rs3752239, rs4147918, rs74176364, and rs117187003) showed no significant relationship with AD risk. Sensitivity analyses confirmed the reliability of the original results, and heterogeneity was largely attributed to deviations from Hardy-Weinberg equilibrium, ethnicity, and variations between individual studies.

CONCLUSION: The available evidence suggests that specific ABCA7 SNPs may be associated with AD risk. Future studies with larger sample sizes will be necessary to confirm these results.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42024540539.

PMID:39484364 | PMC:PMC11524920 | DOI:10.3389/fnagi.2024.1406573

Front Aging Neurosci. 2024 Oct 17;16:1456169. doi: 10.3389/fnagi.2024.1456169. eCollection 2024.

ABSTRACT

BACKGROUND: This study utilized recent advancements in electroencephalography (EEG) technology that enable the measurement of prefrontal event-related potentials (ERPs) to facilitate the early detection of mild cognitive impairment (MCI). We investigated two-channel prefrontal ERP signals obtained from a large cohort of elderly participants and compare among cognitively normal (CN), subjective cognitive decline (SCD), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) groups.

METHODS: Signal processing and ERP component analyses, specifically adapted for two-channel prefrontal ERP signals evoked by the auditory oddball task, were performed on a total of 1,754 elderly participants. Connectivity analyses were conducted to assess brain synchronization, especially in the beta band involving the phase locking value (PLV) and coherence (COH). Time-frequency, time-trial, grand average, and further statistical analyses of the standard and target epochs were also conducted to explore differences among the cognition groups.

RESULTS: The MCI group’s response to target stimuli was characterized by greater response time variability (p < 0.001) and greater variability in the P300 latency (p < 0.05), leading to less consistent responses than those of the healthy control (HC) group (CN+SCD subgroups). In the connectivity analyses of PLV and COH waveforms, significant differences were observed, indicating a loss of synchronization in the beta band in response to standard stimuli in the MCI group. In addition, the absence of event-related desynchronization (ERD) indicated that information processing related to readiness and task performance in the beta band was not efficient in the MCI group. Furthermore, the observed decline in the P200 amplitude as the standard trials progressed suggests the impaired attention and inhibitory processes in the MCI group compared to the HC group. The aMCI subgroup showed high variability in COH values, while the naMCI subgroup showed impairments in their overall behavioral performance.

CONCLUSION: These findings highlight the variability and connectivity measures can be used as markers of early cognitive decline; such measures can be assessed with simple and fast two-channel prefrontal ERP signals evoked by both standard and target stimuli. Our study provides deeper insight of cognitive impairment and the potential use of the prefrontal ERP connectivity measures to assess early cognitive decline.

PMID:39484363 | PMC:PMC11524914 | DOI:10.3389/fnagi.2024.1456169

Dermatol Reports. 2024 Feb 9;16(3):9919. doi: 10.4081/dr.2024.9919. eCollection 2024 Sep 2.

ABSTRACT

The text discusses the role of general practitioners (GPs) in the prevention and early diagnosis of melanoma, a type of skin cancer. It highlights the need for GPs to be able to recognize suspicious skin lesions and refer patients to specialist dermatology centers. However, many GPs lack comprehensive training in diagnosing melanoma. The text mentions that various training courses have been conducted for GPs, but their impact on clinical practice has been limited. The MelaMEd Programme is an e-learning course developed by the Italian Melanoma Intergroup (IMI). The programme aims to provide GPs with comprehensive knowledge of melanoma prevention, diagnosis, and treatment. It includes an e-learning section, and a dedicated platform called MelaMEd platform, which offers a multimedia atlas of melanoma. The objective of the study is to evaluate the impact of the MelaMEd programme on GPs’ diagnostic accuracy, knowledge of melanoma, and management of suspicious lesions. The methodology involves administering pre-training and post-training questionnaires to participants, assessing their diagnostic skills and evaluating the training course’s effectiveness. The study aims to demonstrate the effectiveness of the MelaMEd programme in improving GPs’ ability to recognize and manage melanoma. It also seeks to identify areas for improvement and recommend interventions to enhance diagnostic accuracy. The results will be analyzed statistically using descriptive, univariate, and multivariate analysed methods.

PMID:39484362 | PMC:PMC11526653 | DOI:10.4081/dr.2024.9919

J Am Geriatr Soc. 2024 Oct 31. doi: 10.1111/jgs.19253. Online ahead of print.

ABSTRACT

BACKGROUND: Geriatric Emergency Department (ED) Guidelines recommend optimizing transitions of care for older patients with complex needs. In this study, we investigated referral patterns to interprofessional services, including occupational therapy, physiotherapy, dietician, social work, home care, and specialized geriatric services, among older adults presenting to the ED with high-risk characteristics.

METHODS: We recruited community-dwelling older adults presenting to 10 EDs across Ontario, Quebec, and Newfoundland, Canada, from April 2017 to July 2018. To observe processes of care in the ED, we deployed a two-stage high-risk case-finding and focused comprehensive assessment process based on the interRAI ED-Screener and ED Contact Assessment to identify and characterize older adults at high risk. We analyzed the secondary data using descriptive statistics and logistic regression.

RESULTS: We screened 5265 individuals with the ED Screener, further assessed 1479 with the ED Contact Assessment, and analyzed data from a subset of 1055 community-dwelling older adults assessed with the ED Contact Assessment. Participants in our study sample had a mean age of 83 years, 58% were female, and many had a complex burden of cognitive and functional impairment and social needs. Over half of this high-needs sample were referred to general home care services (62.7%), occupational therapy (59.3%), and physiotherapy services (55.2%), while 16% were referred to specialized geriatric services. We also found a significant positive association between interprofessional referrals and the Assessment Urgency Algorithm and Institutional Risk Scale. The most important determinants of referral to interprofessional services were hospital province, functional, clinical, and social burden and support measures.

CONCLUSIONS: The referral patterns identified suggest that patient needs and risk intensity did not always guide referral patterns in the Canadian EDs investigated. We suggest that EDs critically examine the appropriateness of their documentation and referral systems for supporting person-centered care provision.

PMID:39482258 | DOI:10.1111/jgs.19253

J Cosmet Laser Ther. 2024 Oct 31:1-5. doi: 10.1080/14764172.2024.2420990. Online ahead of print.

ABSTRACT

Jellyfish stings can cause acute inflammatory skin lesions that may hesitate in keloids. Pulsed dye laser (PDL) represents one of the most effective treatments for newly developed keloids. Aim of this study was to evaluate the efficacy of PDL on newly developed keloids specifically induced by jellyfish stings in pediatric patients.We conducted a retrospective observational study on pediatric patients with newly developed keloids from jellyfish stings, treated in the last two years with 595 nm wavelength PDL with a duration of 0.45-1.5 msec, spot-size 7 mm and fluence 8.5-9.5 J/cm². PDL therapy was administered for a mean of 7.4 treatment sessions, every 1-3 months. Two expert dermatologists evaluated the vascularity, pigmentation, height, and pliability of keloids, according to the Vancouver Scar Scale (VSS), pre-and-post treatment. A total of 17 patients (7 males, 10 females) were included in the study, mean age of 11 years. Overall, mean pre-treatment global VSS was 11.0 ± 1.50. After treatment, global VSS was 3.88 ± 1.87. At paired t-test, the difference between pre-treatment and post-treatment was highly statistically significant (p < .0001). Commonly, manipulation and therapeutic intervention on jellyfish scars and keloids is feared. The present study supports the use of PDL in keloids secondary to jellyfish stings, though conducted on a limited number of patients.

PMID:39482257 | DOI:10.1080/14764172.2024.2420990

J Pediatr Urol. 2024 Oct 11:S1477-5131(24)00531-X. doi: 10.1016/j.jpurol.2024.10.010. Online ahead of print.

ABSTRACT

INTRODUCTION: While not entirely understood, nocturnal enuresis (NE) has been considered pathophysiologically distinct from other non-neurogenic voiding disorders. We believe that a significant component of the pathology is due to bladder overactivity. Intravesical Onabotulinumtoxin A (OBTA) injections are utilized in overactive bladder management. We hypothesized that OBTA injections would be efficacious for NE management in pediatric patients with symptoms refractory to conventional therapies.

MATERIALS AND METHODS: A retrospective cohort analysis of patients <18-years-old with primary NE who underwent OBTA injections was performed. Injections were performed by a single surgeon at a single tertiary referral center per standardized protocol. Treatment response was defined as no improvement, greater than 50 % improvement in nightly accidents, or complete resolution of accidents. The primary outcome was treatment success, defined as greater than 50 % improvement in nightly accidents or complete resolution. Secondary outcomes included treatment response duration and complication data. Descriptive and bivariate statistics were performed as indicated. A Kaplan Meier analysis was performed to assess failure free survival following OBTA injection.

RESULTS: Fifty patients met inclusion criteria for this analysis. All patients had trialed at least one lifestyle modification, a bowel regimen, and at least two medications with symptom persistence. The median post-procedure follow-up time was 9.5 months (range 2-82). Improvement in incontinence symptoms compared to pre-operative baseline was seen in 94.0 % of patients, with 58.0 % demonstrating complete resolution of incontinence through most recent follow up. There was no difference in improvement rates or resolution rates in male vs female gender. The median failure free survival identified on Kaplan Meier analysis was 12.5 months (Figure 1) Minor post-operative complications (4 urinary tract infections; 1 retentive episode necessitating catheterization) were identified in five patients. There were no major post-operative complications.

DISCUSSION: Efficacy of OBTA injections was high, with treatment success demonstrated in 94 % of patients and failure free survival of 12.5 months. This procedure also demonstrated a favorable safety profile, with few minor post-operative complications identified. These results indicate that this procedure may be a beneficial therapeutic option for patients with NE refractory to multiple lines of conventional therapy. This study is limited by its retrospective design with short median follow up and potential for recall bias. It is strengthened by its large sample size and novelty.

CONCLUSIONS: To our knowledge, this is the first analysis of the efficacy of OBTA injections for management of primary NE. A follow up clinical trial is essential to further understand this association.

PMID:39482187 | DOI:10.1016/j.jpurol.2024.10.010

Child Abuse Negl. 2024 Oct 30:107099. doi: 10.1016/j.chiabu.2024.107099. Online ahead of print.

ABSTRACT

RATIONALE: Most child well-being and childhood adversity research is informed by proxy informants such as parents or teachers rather than children and youth. This may be due to concerns about perceived sensitivity, challenges accessing and engaging with children in research, ethical considerations, and apprehensions about causing undue harm and distress. This study aimed to understand adolescents’ identification of, and reactions to, questions in the context of participating in a survey of well-being and adversity.

OBJECTIVES: The aim of this study was to enhance our understanding of how adolescents identify and respond to potentially upsetting questions about well-being and life experiences, including childhood adversity.

METHOD: Data were from 1002 adolescent respondents aged 14 to 17 years. The Well-being and Experiences (WE) survey assessed several domains of life, including general health and well-being and early life adversity. Data were analyzed using descriptive statistics, logistic regression models, and thematic analysis approaches.

RESULTS: Few adolescent respondents reported feeling upset when completing the survey (11.2 %). Among those who reported feeling upset, 92.0 % indicated that it was still important to ask those upsetting questions, and only two respondents (1.8 %) thought upsetting questions should be removed. Ten themes emerged from the adolescents’ reflections on self-reported upsetting questions, including identity and life satisfaction, motivation, mental health, and school; childhood adversity was not primarily identified.

CONCLUSIONS: Findings indicate that conducting research on well-being and childhood adversity directly with adolescents is feasible and minimally distressing. Future research should consider how to engage youth directly in research to understand better the scope and outcomes associated with childhood adversity.

PMID:39482185 | DOI:10.1016/j.chiabu.2024.107099