Nevin Manimala

Bioinformatics. 2022 Nov 16:btac728. doi: 10.1093/bioinformatics/btac728. Online ahead of print.

ABSTRACT

MOTIVATION: Association testing on genome-wide association studies (GWAS) data is commonly performed under a single (mostly additive) genetic model framework. However, the underlying true genetic mechanisms are often unknown in practice for most complex traits. When the employed inheritance model deviates from the underlying model, statistical power may be reduced. To overcome this challenge, an integrative association test that directly infers the underlying genetic model from GWAS data has previously been proposed for single-SNP analysis.

RESULTS: In this article, we propose a Cauchy combination Genetic Model-based association test (CauchyGM) under a generalized linear model framework for SNP-set level analysis. CauchyGM does not require prior knowledge on the underlying inheritance patterns of each SNP. It performs a score test which first estimates an individual p-value of each SNP in a SNP-set with both minor allele frequency (MAF) > 1% and three genotypes and further aggregates the rest SNPs using SKAT. CauchyGM then combines the correlated p-values across multiple SNPs and different genetic models within the set using Cauchy Combination Test. To further accommodate both sparse and dense signal patterns, we also propose an omnibus association test (CauchyGM-O) by combining CauchyGM with SKAT and burden test. Our extensive simulations show that both CauchyGM and CauchyGM-O maintain type I error well at the genome-wide significance level and provide substantial power improvement compared to existing methods. We apply our methods to a pharmacogenomic GWAS data from a large cardiovascular randomized clinical trial. Both CauchyGM and CauchyGM-O identify several novel genome-wide significant genes.

AVAILABILITY AND IMPLEMENTATION: The R package CauchyGM is publicly available on github: https://github.com/ykim03517/CauchyGM.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36383169 | DOI:10.1093/bioinformatics/btac728

Bioinformatics. 2022 Nov 16:btac736. doi: 10.1093/bioinformatics/btac736. Online ahead of print.

ABSTRACT

MOTIVATION: Single-cell multi-omics sequencing techniques have rapidly developed in the past few years. Clustering analysis with single-cell multi-omics data may give us novel perspectives to dissect cellular heterogeneity. However, multi-omics data have the properties of inherited large dimension, high sparsity and existence of doublets. Moreover, representations of different omics from even the same cell follow diverse distributions. Without proper distribution alignment techniques, clustering methods will encounter less separable clusters easily affected by less informative omics data.

RESULTS: We developed MoClust, a novel joint clustering framework that can be applied to several types of single-cell multi-omics data. A selective automatic doublet detection module that can identify and filter out doublets is introduced in the pretraining stage to improve data quality. Omics-specific autoencoders are introduced to characterize the multi-omics data. A contrastive learning way of distribution alignment is adopted to adaptively fuse omics representations into an omics-invariant representation. This novel way of alignment boosts the compactness and separableness of clusters, while accurately weighting the contribution of each omics to the clustering object. Extensive experiments, over both simulated and real multi-omics datasets, demonstrated the powerful alignment, doublet detection and clustering ability features of MoClust.

AVAILABILITY: An implementation of MoClust is available from https://doi.org/10.5281/zenodo.7306504.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36383167 | DOI:10.1093/bioinformatics/btac736

BMC Urol. 2022 Nov 15;22(1):183. doi: 10.1186/s12894-022-01142-0.

ABSTRACT

OBJECTIVE: To compare the outcomes of FURSL and m-PNL in the management of upper calyceal calculi larger than 2 cm.

METHODS: A total of 75 patients with upper calyceal calculi larger than 2 cm that were treated by FURSL (n = 37) or mini-PNL (n = 38) were retrospectively analysed. The mean age, sex, stone burden, operative time, complications, length of hospitalization, and stone-free rate (SFR) were compared between the groups. The success of the procedure was defined by the absence of residual stones or residual fragments smaller than 4 mm on computed tomography at 4 weeks postoperatively.

RESULTS: The two groups had comparable preoperative parameters. The mean operative time was significantly longer in the mini-PNL group than in the FURSL group (87.8 vs. 69.8 min, p < 0.001). The length of hospitalization was greater in the mini-PNL group than in the FURSL group (2.5 vs. 1.3 days, p < 0.001). Although the perioperative complication rate was higher in the mini-PNL group (23.7%) than in the FURSL group (13.5%), this difference was not statistically significant (p = 0.258). The SFR for the mini-PNL group was 89.5%, and that of the FURSL group was 81.1%; the difference was not significantly different (p = 0.304).

CONCLUSIONS: Both FURSL and mini-PNL are effective and safe for the management of upper calyceal calculi larger than 2 cm. Of these two procedures, mini-PNL is less time consuming, FURSL is associated with faster recovery. FURSL can be considered a good alternative treatment in selected patients.

PMID:36380338 | DOI:10.1186/s12894-022-01142-0

BMC Med. 2022 Nov 15;20(1):444. doi: 10.1186/s12916-022-02656-y.

ABSTRACT

BACKGROUND: There is growing evidence that patients recovering after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have a variety of acute sequelae including newly diagnosed diabetes. However, the risk of diabetes in the post-acute phase is unclear. To solve this question, we aimed to determine if there was any association between status post-coronavirus disease (COVID-19) infection and a new diagnosis of diabetes.

METHODS: We performed a systematic review and meta-analysis of cohort studies assessing new-onset diabetes after COVID-19. PubMed, Embase, Web of Science, and Cochrane databases were all searched from inception to June 10, 2022. Three evaluators independently extracted individual study data and assessed the risk of bias. Random-effects models estimated the pooled incidence and relative risk (RR) of diabetes compared to non-COVID-19 after COVID-19.

RESULTS: Nine studies with nearly 40 million participants were included. Overall, the incidence of diabetes after COVID-19 was 15.53 (7.91-25.64) per 1000 person-years, and the relative risk of diabetes after COVID-19 infection was elevated (RR 1.62 [1.45-1.80]). The relative risk of type 1 diabetes was RR=1.48 (1.26-1.75) and type 2 diabetes was RR=1.70 (1.32-2.19), compared to non-COVID-19 patients. At all ages, there was a statistically significant positive association between infection with COVID-19 and the risk of diabetes: <18 years: RR=1.72 (1.19-2.49), ≥18 years: RR=1.63 (1.26-2.11), and >65 years: RR=1.68 (1.22-2.30). The relative risk of diabetes in different gender groups was about 2 (males: RR=2.08 [1.27-3.40]; females: RR=1.99 [1.47-2.80]). The risk of diabetes increased 1.17-fold (1.02-1.34) after COVID-19 infection compared to patients with general upper respiratory tract infections. Patients with severe COVID-19 were at higher risk (RR=1.67 [1.25-2.23]) of diabetes after COVID-19. The risk (RR=1.95 [1.85-2.06]) of diabetes was highest in the first 3 months after COVID-19. These results remained after taking confounding factors into account.

CONCLUSIONS: After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes. Particular attention should be paid during the first 3 months of follow-up after COVID-19 for new-onset diabetes.

PMID:36380329 | DOI:10.1186/s12916-022-02656-y

BMC Oral Health. 2022 Nov 15;22(1):493. doi: 10.1186/s12903-022-02563-x.

ABSTRACT

BACKGROUND: Short-term sintering may offer advantages including saving time and energy but there is limited evidence on the effect that altering sintering time has on the accuracy of monolithic zirconia crowns. The purpose of this in vitro study was to investigate the effect of shortened sintering time on the marginal and internal fit of 3Y-TZP and 4Y-TZP monolithic crowns.

METHODS: Sixty monolithic zirconia crowns were fabricated for the maxillary first molar tooth on the prefabricated implant abutment. Groups were created according to the material composition: 3Y-TZP Generation 1, 3Y-TZP Generation 2 and 4Y-TZP. Two different sintering protocols were performed: same final sintering temperature (1500 °C) and various rates of heating (10 °C/min and 40 °C/min), cooling down speed (- 10 °C/min and – 40 °C/min), holding time (45 and 120 minutes), and total sintering time (approximately 2 and 7 hours, respectively). The marginal and internal fit of the crowns were determined using the silicone replica technique. Comparisons between groups were analyzed using two-way ANOVA. Pairwise multiple comparisons were performed using t-test (p < 0.05).

RESULTS: The mean marginal gap values of 4Y-TZP zirconia revealed statistically significant increase for the short-term sintering protocol (p < 0.0001), while no difference was observed between the sintering protocols for the mean marginal gap values of 3Y-TZP groups. Although all groups showed clinically acceptable gap values, altering the sintering time had an effect on marginal fit of the crowns manufactured from 4Y-TZP zirconia.

CONCLUSIONS: Shortening the sintering time may lead to differences within clinically acceptable limits. The manufacturer’s recommendations according to material composition should be implemented with care.

PMID:36380324 | DOI:10.1186/s12903-022-02563-x

Malar J. 2022 Nov 15;21(1):334. doi: 10.1186/s12936-022-04363-8.

ABSTRACT

BACKGROUND: Malaria remains a serious health problem in the southern border provinces of Thailand. The issue areas can be identified using an appropriate statistical model. This study aimed to investigate malaria for its spatial occurrence and incidence rate in the southernmost provinces of Thailand.

METHODS: The Thai Office of Disease Prevention and Control, Ministry of Public Health, provided total hospital admissions of malaria cases from 2008 to 2020, which were classified by age, gender, and sub-district of residence. Sixty-two sub-districts were excluded since they had no malaria cases. A logistic model was used to identify spatial occurrence patterns of malaria, and a log-linear regression model was employed to model the incidence rate after eliminating records with zero cases.

RESULTS: The overall occurrence rate was 9.8% and the overall median incidence rate was 4.3 cases per 1,000 population. Malaria occurence peaked at young adults aged 20-29, and subsequently fell with age for both sexes, whereas incidence rate increased with age for both sexes. Malaria occurrence and incidence rates fluctuated; they appeared to be on the decline. The area with the highest malaria occurrence and incidence rate was remarkably similar to the area with the highest number of malaria cases, which were mostly in Yala province’s sub-districts bordering Malaysia.

CONCLUSIONS: Malaria is a serious problem in forest-covered border areas. The correct policies and strategies should be concentrated in these areas, in order to address this condition.

PMID:36380322 | DOI:10.1186/s12936-022-04363-8

BMC Pediatr. 2022 Nov 15;22(1):661. doi: 10.1186/s12887-022-03717-0.

ABSTRACT

BACKGROUND: Iron deficiency is one of the most important factors of anemia which is caused by poor iron intake. In addition, children need more iron because of their rapid growth. On the other side, daily intake of iron is also recommended as a standard approach for the treatment and prevention of iron deficiency anemia. In Ethiopia, although more than half of children 6-59 months of age were affected by anemia, the magnitude and factors associated with iron intake among them are understudied. Therefore this study aimed to assess the magnitude and community and individual level determinants of iron intake among 6-59 months children in Ethiopia.

METHODS: Demographic and Health Survey datasets (EDHS) were used for this study. The data were weighted using sampling weight to get valid statistical estimates. The total weighted samples of 9,218 children aged 6-59 months were included. A multilevel binary logistic regression model was fitted to identify factors associated with iron intake among 6-59 months of children in Ethiopia. In the final model adjusted odds ratio with a 95% confidence interval and p-value < 0.05 was taken to declare statistical significance.

RESULTS: The magnitude of iron intake among children 6-59 months in Ethiopia was 9.24% (95% CI: 8.31%, 10.15%). Individual level variables such as having at least one antenatal care visit (ANC) [AOR = 1.27; 95%CI; 1.01, 1.61], having health institution delivery [AOR = 1.46; 95%CI;1.04, 2.04], age of children ≥ 24 months [AOR = 1.82; 95%CI; 1.29, 2.57], being female child [AOR = 0.81; 95%CI; 0.67, 0.99], being greater than three birth order [AOR = 0.73, 95%CI: 0.55, 0.98], whereas community level variables such as living in large central regions [AOR = 3.68; 95%CI; 1.47, 9.21], and living in community with high women education [AOR = 1.96; 95%CI; 1.28, 2.98] have an association with iron supplements among children 6-59 months years old in Ethiopia.

CONCLUSION AND RECOMMENDATIONS: The magnitude of iron intake among children 6-59 months old in Ethiopia is relatively low. Individual level factors such as; ANC visit, institution delivery, age of children, sex of the child, and birth order as well as; community level variables such as regions, and community women’s education have a significant association with iron intake among children 6-59 months in Ethiopia. Prior attention should be given for under two years old children, children greater than three birth orders, and children living in small peripheral regions. Moreover, policymakers and other stakeholders had better plan and implement programs that empower women, enhance ANC visits, and health institution delivery to have a sustainable increment in iron intake for children in Ethiopia.

PMID:36380321 | DOI:10.1186/s12887-022-03717-0

Respir Res. 2022 Nov 15;23(1):315. doi: 10.1186/s12931-022-02222-3.

ABSTRACT

BACKGROUND: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients.

METHODS: This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death.

RESULTS: Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11-0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43-4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course.

CONCLUSIONS: Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

PMID:36380316 | DOI:10.1186/s12931-022-02222-3

BMC Nurs. 2022 Nov 16;21(1):315. doi: 10.1186/s12912-022-01071-1.

ABSTRACT

BACKGROUND: Near-miss organizational learning is important for perspective and proactive risk management. Although nursing organizations are the largest component of the healthcare system and act as the final safety barrier, there is little research about the current status of near-miss organizational learning. Thus, we conducted this study to explore near-miss organizational learning in a Chinese nursing organization and offer suggestions for future improvement.

METHODS: This was a mixed methods study with an explanatory sequence. It was conducted in a Chinese nursing organization of a tertiary hospital under the guidance of the 4I Framework of Organizational Learning. The quantitative study surveyed 600 nurses by simple random sampling. Then, we applied purposive sampling to recruit 16 nurses across managerial levels from low-, middle- and high-scored nursing units and conducted semi-structured interviews. Descriptive statistics, structured equation modelling and content analysis were applied in the data analysis. The Good Reporting of A Mixed Methods Study (GRAMMS) checklist was used to report this study.

RESULTS: Only 33% of participants correctly recognized near-misses, and 4% of participants always reported near-misses. The 4I Framework of Organizational Learning was verified in the surveyed nursing organization (χ² = 0.775, p = 0.379, RMSEA < 0.01). The current organizational learning behaviour was not conducive to near-miss organizational learning due to poor group-level learning (β_GG = 0.284) and poor learning absorption (β_Misalignment= -0.339). In addition, the researchers developed 13 codes, 9 categories and 5 themes to depict near-miss organizational learning, which were characterized by nurses’ unfamiliarity with near-misses, preferences and the dominance of first-order problem-solving behaviour, the suspension of near-miss learning at the group level and poor learning absorption.

CONCLUSION: The performance of near-miss organizational learning is unsatisfactory across all levels in surveyed nursing organization, especially with regard to group-level learning and poor learning absorption. Our research findings offer a scientific and comprehensive description of near-miss organizational learning and shed light on how to measure and improve near-miss organizational learning in the future.

PMID:36380309 | DOI:10.1186/s12912-022-01071-1

BMC Public Health. 2022 Nov 15;22(1):2081. doi: 10.1186/s12889-022-14289-0.

ABSTRACT

BACKGROUND: One in three women from lower and middle-income countries are subjected to physical and/or sexual intimate partner violence (IPV) in their life span. Prior studies have highlighted a range of adverse health impacts of sexual IPV. However, less is known about the link between multiple high-risk fertility behaviours and sexual intimate partner violence. The present study examines the statistical association between multiple high-risk fertility behaviours and sexual intimate partner violence among women in India.

METHODS: The present study used a nationally representative dataset, the National Family Health Survey (NFHS-4) 2015-16. A total of 23,597 women were included in the study; a subsample of married women of reproductive age who have had at least one child 5 years prior to the survey and who had valid information about sexual IPV. Logistic regression models were employed alongside descriptive statistics.

RESULTS: Approximately 7% of women who are or had been married face sexual IPV. The prevalence of sexual violence was higher among women who had short birth intervals and women who had given birth more than three times (12%). Around 11% of women who had experienced any high-risk fertility behaviours also experienced sexual violence. The unadjusted association suggested that multiple high-risk fertility behaviours were 32% (UORs = 1.32, 95% CI: 1.16-1.50) higher for those women who experienced sexual violence. After adjusting for other sociodemographic variables, except for women’s education and wealth quantile, the odds of multiple high-risk fertility behaviours were 16% (AOR = 1.16; 95% CI: 1.02-1.34) higher among women who faced sexual violence. The inclusion of women’s educational attainment and wealth status in the model made the association between sexual IPV and high-risk fertility behaviours insignificant.

CONCLUSION: Sexual intimate partner violence is statistically associated with high-risk fertility behaviours among women in India. Programs and strategies designed to improve women’s reproductive health should investigate the different dimensions of sexual IPV in India.

PMID:36380301 | DOI:10.1186/s12889-022-14289-0