Category: Statistics

Biostatistics. 2023 Dec 23:kxad034. doi: 10.1093/biostatistics/kxad034. Online ahead of print.

ABSTRACT

With rapid development of techniques to measure brain activity and structure, statistical methods for analyzing modern brain-imaging data play an important role in the advancement of science. Imaging data that measure brain function are usually multivariate high-density longitudinal data and are heterogeneous across both imaging sources and subjects, which lead to various statistical and computational challenges. In this article, we propose a group-based method to cluster a collection of multivariate high-density longitudinal data via a Bayesian mixture of smoothing splines. Our method assumes each multivariate high-density longitudinal trajectory is a mixture of multiple components with different mixing weights. Time-independent covariates are assumed to be associated with the mixture components and are incorporated via logistic weights of a mixture-of-experts model. We formulate this approach under a fully Bayesian framework using Gibbs sampling where the number of components is selected based on a deviance information criterion. The proposed method is compared to existing methods via simulation studies and is applied to a study on functional near-infrared spectroscopy, which aims to understand infant emotional reactivity and recovery from stress. The results reveal distinct patterns of brain activity, as well as associations between these patterns and selected covariates.

PMID:38141227 | DOI:10.1093/biostatistics/kxad034

Toxicol Sci. 2023 Dec 23:kfad134. doi: 10.1093/toxsci/kfad134. Online ahead of print.

ABSTRACT

Systematic review and evaluation of mechanistic evidence using the Key Characteristics approach was proposed by the International Agency for Research on Cancer (IARC) in 2012 and used by the IARC Monographs Working Groups since 2015. Key Characteristics are ten features of agents known to cause cancer in humans. From 2015 to 2022 a total of 19 Monographs (73 agents combined) used Key Characteristics for cancer hazard classification. We hypothesized that a retrospective analysis of applications of the Key Characteristics approach to cancer hazard classification using heterogenous mechanistic data on diverse agents would be informative for systematic reviews in decision-making. We extracted information on the conclusions, data types, and the role mechanistic data played in the cancer hazard classification from each Monograph. Statistical analyses identified patterns in the use of Key Characteristics, as well as trends and correlations among Key Characteristics, data types, and ultimate decisions. Despite gaps in data for many agents and Key Characteristics, several significant results emerged. Mechanistic data from in vivo animal, in vitro animal and in vitro human studies was most impactful for concluding that an agent could cause cancer via a Key Characteristic. To exclude the involvement of a Key Characteristic, data from large-scale systematic in vitro testing programs such as ToxCast were most informative. Overall, increased availability of systemized data streams, such as human in vitro data, would provide the basis for confident conclusions about both positive and negative associations and constitute relative contributions of various sources of weight in expert judgments.

PMID:38141214 | DOI:10.1093/toxsci/kfad134

Bioinformatics. 2023 Dec 23:btad772. doi: 10.1093/bioinformatics/btad772. Online ahead of print.

ABSTRACT

MOTIVATION: The utilization of single-cell bisulfite sequencing (scBS-seq) methods allows for precise analysis of DNA methylation patterns at the individual cell level, enabling the identification of rare populations, revealing cell-specific epigenetic changes, and improving differential methylation analysis. Nonetheless, the presence of sparse data and an overabundance of zeros and ones, attributed to limited sequencing depth and coverage, frequently results in reduced precision accuracy during the process of differential methylation detection using scBS-seq. Consequently, there is a pressing demand for an innovative differential methylation analysis approach that effectively tackles these data characteristics and enhances recognition accuracy.

RESULTS: We propose a novel beta mixture approach called scDMV for analyzing methylation differences in single-cell bisulfite sequencing data, which effectively handles excess zeros and ones and accommodates low-input sequencing. Our extensive simulation studies demonstrate that the scDMV approach outperforms several alternative methods in terms of sensitivity, precision, and controlling the false positive rate. Moreover, in real data applications, we observe that scDMV exhibits higher precision and sensitivity in identifying differentially methylated regions, even with low-input samples. Additionally, scDMV reveals important information for GO enrichment analysis with single-cell whole genome sequencing data that is often overlooked by other methods.

AVAILABILITY: The scDMV method, along with a comprehensive tutorial, can be accessed as an R package on the following GitHub repository: https://github.com/PLX-m/scDMV.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38141207 | DOI:10.1093/bioinformatics/btad772

J AOAC Int. 2023 Dec 23:qsad137. doi: 10.1093/jaoacint/qsad137. Online ahead of print.

ABSTRACT

BACKGROUND: Botanical reference materials (BRMs) generally account for the species, cultivar, and year and location of harvest that result in variability in the chemical composition that may lead to statistically significant differences using chemometric methods.

OBJECTIVE: To Compare the chemical composition of 5 species of Actaea root BRMs, 4 herbal sources of A. racemosa root BRMs, and A. racemosa BRMS, and commercial roots and supplements using chemometric methods and selected pre-processing approaches.

METHODS: Samples were analyzed by flow injection mass spectrometry (FIMS), principal component analysis (PCA), and factorial multivariate analysis of variance (mANOVA).

RESULTS: Statistically significant (p = 0.05) compositional differences were found between 3 genera (Actaea, Panax, and Ginkgo), 5 species of Actaea (A. racemosa, A. cimicifuga, A. dahurica, A. pachypoda, and A. rubra) root BRMs, 4 herbal sources of A. racemosa root BRMs, and A. racemosa BRMS and commercial roots and supplements. The variability of 6% of the BRM variables was found to be quantitatively conserved and reduced the compositional differences between the 4 sources of root BRMs. Compositional overlap of A. racemosa and other Actaea BRMs was influenced by variation in technical repeats, pre-processing methods, selection of variables, and selection of confidence limits. Sensitivity ranged from 94% to 97% and specificity ranged from 21% to 89% for the pre-processing protocols tested.

CONCLUSION: Environmental, genetic, and chemometric factors can influence discrimination between species and authentic botanical reference materials.

HIGHLIGHTS: Frequency distribution plots derived from soft independent modeling of class analogy provide excellent means for understanding the impact of experimental factors.

PMID:38141206 | DOI:10.1093/jaoacint/qsad137

Curr Drug Targets. 2023 Dec 21. doi: 10.2174/0113894501272740231219072525. Online ahead of print.

ABSTRACT

INTRODUCTION: There is a growing interest in the considerable benefits of grape products intake, as some studies have indicated that they may improve cardiometabolic risk factors. However, the widespread impact of grape products on the anthropometric indices is not fully resolved.

METHOD: The purpose of this systematic review and meta-analysis was to examine the effects of grape products intake on anthropometric indices in adults. Randomized controlled trials (RCT) examining the effects of grape products intake on anthropometric indices, published up to December 2021, were identified through PubMed, SCOPUS, and ISI Web of Science databases. 30 studies with 35 effect sizes, including 1284 participants (708 cases and 576 controls), were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence interval (CI).

RESULT: The outcomes have revealed grape products intake to significantly decrease body weight (p = 0.001) and body mass index (p = 0.004) in obese participants, and also, a greater effect was observed when grape seed extract was used.

CONCLUSION: Our study suggests that grape products intake may help to decrease body weight in obese participants. Future large RCTs with longer duration and obese populations are needed to expand our findings.

PMID:38141198 | DOI:10.2174/0113894501272740231219072525

Acta Otolaryngol. 2023 Dec 23:1-5. doi: 10.1080/00016489.2023.2279266. Online ahead of print.

ABSTRACT

Background: No selection criteria for the four bone conduction hearing devices yet.Aims/Objectives: To compare effectiveness of four bone conduction hearing devices in patients with bilateral Congenital Malformation of the Middle and Outer Ear (CMMOE).Material and Methods: 24 Patients (25 ears) were divided into five groups: 1) Bone Anchored Hearing Aid softband (BAHA-s), 2) BAHA implant (BAHA-i nested within group 1), 3) Vibration Sound Bridge implant (VSB-i), 4) Bone Bridge implant (BB-i), and 5) Bone Conduction Hearing Aid softband (BCHA-s). One patient implanted VSB and BB. Auditory parameters were compared: 1. Communication, 2. Average Air Conduction Thresholds (ACT) of pure tone, 3. Sentence Recognition Scores in quiet (SRS-q) and noisy (SRS-n) settings. The one-way analysis of variance (ANOVA) were employed to compare the differences in ACT and SRS-q/n among the groups, a statistical significance level of P < 0.05 was applied.Results: After hearing aid usage, all 24 patients (25 ears) reached or approached the normal in communication (i.e. from difficult to smooth), average ACT and SRS-q/SRS-n (no difference among groups, p > 0 .05). However, there was the difference in the optimal frequency of ACT and the absolute value of SRS-q/SRS-n for VSB/BAHA implants was higher than that for BB and BAHA softband.Conclusions and Significance: The precise selection of the four hearing devices mainly depends on patient’s hearing level, the optimal frequency of ACT and absolute values of SRS-q/SRS-n.

PMID:38141167 | DOI:10.1080/00016489.2023.2279266

Br J Sociol. 2023 Dec 23. doi: 10.1111/1468-4446.13070. Online ahead of print.

ABSTRACT

While gender inequalities in employment (paid public work) and domestic and reproductive labour (unpaid private work) are a prominent focus within the sociological literature, gender inequalities in volunteering (unpaid public work) have received much less scholarly attention. We analyse a unique longitudinal dataset of volunteer leaders, that follows through time every individual to have served as a board member (trustee) for a charity in England and Wales between 2010 and 2023, to make three foundational contributions to our understanding of gender inequalities in unpaid public work. First, the salience of vertical gender stratification and horizontal gender segmentation in trusteeship shows that gendered inequalities in work extend to public work in general-encompassing unpaid public work, and not only paid public work. In terms of gender segmentation, we find that women are over-represented as trustees in a small number of fields of charitable activity but under-represented across the majority of fields. In terms of gender stratification, we find that women are under-represented on the boards of the largest charities; under-represented as chairs of trustee boards; and particularly under-represented as chairs of the largest charities. Second, the dynamics underlying gendered differences in unpaid public work, which show higher rates of resignation for women trustees, resonate with research on paid employment which emphasises the importance of attrition to an understanding of how gendered inequalities in work are reproduced. This means that increasing the retention of women, not only the recruitment of women, becomes central to the policy agenda. Third, we show that there has been a decline in gender stratification and gender segmentation in trusteeship since 2010. This decline over time in gendered inequalities in unpaid public work provides an interesting counterpoint to influential research documenting a ‘stall’ in the reduction of gendered inequalities in paid employment.

PMID:38141163 | DOI:10.1111/1468-4446.13070

Eur J Pediatr. 2023 Dec 23. doi: 10.1007/s00431-023-05376-4. Online ahead of print.

ABSTRACT

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype-phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val). Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype-phenotype correlations are needed.

PMID:38141137 | DOI:10.1007/s00431-023-05376-4

J Neurol. 2023 Dec 23. doi: 10.1007/s00415-023-12128-9. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the factors influencing relapse and prognosis in patients with primary autoimmune cerebellar ataxia (PACA), an area previously not well understood.

METHODS: This prospective cohort study included patients who satisfied the modified diagnostic criteria of PACA. A modified Rankin scale score ≤ 2 at the last follow-up was defined as a favorable prognosis. Cox and Logistic regression were utilized to identify relapsing and prognostic factors, respectively.

RESULTS: A total of 68 patients were included and 35.3% were male. The median onset age was 42.9 years (IQR 22.1-54.0). Neuronal autoantibodies were detected in 33 (50.8%) patients. Of the 65 patients who received first-line immunotherapy, 55 (84.6%) were responsive and 10 (15.4%) were not. Responsiveness to first-line immunotherapy emerged as an independent factor for favorable prognosis (HR 16.762; 95% CI 2.877-97.655; p = 0.002), as did the absence of peripheral neuropathy/radiculopathy (HR 14.286; 95% CI 2.41-83.333; p = 0.003). Relapses occurred in 19 (27.9%) patients. Onset age ≤ 43 years (HR 5.245; 95% CI 1.499-18.35; p = 0.009), presence of peripheral neuropathy/radiculopathy (HR 4.280; 95% CI 1.622-11.298; p = 0.003) and elevated cerebrospinal fluid (CSF) protein concentration (HR 3.443; 95% CI 1.083-10.951; p = 0.036) were statistically significant relapsing factors.

CONCLUSION: This study identified younger onset age, presence of peripheral neuropathy/radiculopathy and elevated CSF protein concentration as relapsing factors, and absence of peripheral neuropathy/radiculopathy and responsiveness to first-line immunotherapy as independent factors for favorable prognosis in PACA patients. These findings may guide individualized treatment strategies and potentially improve patient outcomes.

PMID:38141127 | DOI:10.1007/s00415-023-12128-9

Appl Health Econ Health Policy. 2023 Dec 23. doi: 10.1007/s40258-023-00856-y. Online ahead of print.

NO ABSTRACT

PMID:38141116 | DOI:10.1007/s40258-023-00856-y