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Nevin Manimala Statistics

PCA outperforms popular hidden variable inference methods for molecular QTL mapping

Genome Biol. 2022 Oct 11;23(1):210. doi: 10.1186/s13059-022-02761-4.

ABSTRACT

BACKGROUND: Estimating and accounting for hidden variables is widely practiced as an important step in molecular quantitative trait locus (molecular QTL, henceforth “QTL”) analysis for improving the power of QTL identification. However, few benchmark studies have been performed to evaluate the efficacy of the various methods developed for this purpose.

RESULTS: Here we benchmark popular hidden variable inference methods including surrogate variable analysis (SVA), probabilistic estimation of expression residuals (PEER), and hidden covariates with prior (HCP) against principal component analysis (PCA)-a well-established dimension reduction and factor discovery method-via 362 synthetic and 110 real data sets. We show that PCA not only underlies the statistical methodology behind the popular methods but is also orders of magnitude faster, better-performing, and much easier to interpret and use.

CONCLUSIONS: To help researchers use PCA in their QTL analysis, we provide an R package PCAForQTL along with a detailed guide, both of which are freely available at https://github.com/heatherjzhou/PCAForQTL . We believe that using PCA rather than SVA, PEER, or HCP will substantially improve and simplify hidden variable inference in QTL mapping as well as increase the transparency and reproducibility of QTL research.

PMID:36221136 | DOI:10.1186/s13059-022-02761-4

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Nevin Manimala Statistics

A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients

BMC Musculoskelet Disord. 2022 Oct 12;23(1):908. doi: 10.1186/s12891-022-05846-0.

ABSTRACT

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages’ function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages.

METHODS: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined.

RESULTS: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients’ macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients’ group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI).

CONCLUSION: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients’ macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients’ macrophages.

PMID:36221125 | DOI:10.1186/s12891-022-05846-0

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Nevin Manimala Statistics

Cross-watershed distribution pattern challenging the elimination of Oncomelania hupensis, the intermediate host of Schistosoma japonica, in Sichuan province, China

Parasit Vectors. 2022 Oct 11;15(1):363. doi: 10.1186/s13071-022-05496-0.

ABSTRACT

BACKGROUND: Snail control is critical to schistosomiasis control efforts in China. However, re-emergence of Oncomelania hupensis is challenging the achievements of schistosomiasis control. The present study aimed to test whether the amphibious snails can spread across watersheds using a combination of population genetics and geographic statistics.

METHODS: The digital maps and attributes of snail habitats were obtained from the national survey on O. hupensis. Snail sampling was performed in 45 counties of Sichuan Province. The cox1 gene of specimens was characterized by sequencing. Unique haplotypes were found for phylogenetic inference and mapped in a geographical information system (GIS). Barriers of gene flow were identified by Monmonier’s maximum difference algorithm. The watercourses and watersheds in the study area were determined based on a digital elevation model (DEM). Plain areas were defined by a threshold of slope. The slope of snail habitats was characterized and the nearest distance to watercourses was calculated using a GIS platform. Spatial dynamics of high-density distributions were observed by density analysis of snail habitats.

RESULTS: A total of 422 cox1 sequences of O. hupensis specimens from 45 sampling sites were obtained and collapsed into 128 unique haplotypes or 10 clades. Higher haplotype diversity in the north of the study area was observed. Four barriers to gene flow, leading to five sub-regions, were found across the study area. Four sub-regions ran across major watersheds, while high-density distributions were confined within watersheds. The result indicated that snails were able to disperse across low-density areas. A total of 63.48% habitats or 43.29% accumulated infested areas were distributed in the plain areas where the overall slope was < 0.94°. Approximately 90% of snail habitats were closer to smaller watercourses. Historically, high-density areas were mainly located in the plains, but now more were distributed in hilly region.

CONCLUSIONS: Our study showed the cross-watershed distribution of Oncomelania snails at a large scale. Natural cross-watershed spread in plains and long-distance dispersal by humans and animals might be the main driver of the observed patterns. We recommend cross-watershed joint control strategies for snail and schistosomiasis control.

PMID:36221118 | DOI:10.1186/s13071-022-05496-0

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Nevin Manimala Statistics

Managing clustering effects and learning effects in the design and analysis of randomised surgical trials: a review of existing guidance

Trials. 2022 Oct 11;23(1):869. doi: 10.1186/s13063-022-06743-6.

ABSTRACT

BACKGROUND: The complexities associated with delivering randomised surgical trials, such as clustering effects, by centre or surgeon, and surgical learning, are well known. Despite this, approaches used to manage these complexities, and opinions on these, vary. Guidance documents have been developed to support clinical trial design and reporting. This work aimed to identify and examine existing guidance and consider its relevance to clustering effects and learning curves within surgical trials.

METHODS: A review of existing guidelines, developed to inform the design and analysis of randomised controlled trials, is undertaken. Guidelines were identified using an electronic search, within the Equator Network, and by a targeted search of those endorsed by leading UK funding bodies, regulators, and medical journals. Eligible documents were compared against pre-specified key criteria to identify gaps or inconsistencies in recommendations.

RESULTS: Twenty-eight documents were eligible (12 Equator Network; 16 targeted search). Twice the number of guidance documents targeted design (n/N=20/28, 71%) than analysis (n/N=10/28, 36%). Managing clustering by centre through design was well documented. Clustering by surgeon had less coverage and contained some inconsistencies. Managing the surgical learning curve, or changes in delivery over time, through design was contained within several documents (n/N=8/28, 29%), of which one provided guidance on reporting this and restricted to early phase studies only. Methods to analyse clustering effects and learning were provided in five and four documents respectively (N=28).

CONCLUSIONS: To our knowledge, this is the first review as to the extent to which existing guidance for designing and analysing randomised surgical trials covers the management of clustering, by centre or surgeon, and the surgical learning curve. Twice the number of identified documents targeted design aspects than analysis. Most notably, no single document exists for use when designing these studies, which may lead to inconsistencies in practice. The development of a single document, with agreed principles to guide trial design and analysis across a range of realistic clinical scenarios, is needed.

PMID:36221107 | DOI:10.1186/s13063-022-06743-6

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Nevin Manimala Statistics

Does eating behaviour among adolescents and young adults seeking obesity treatment differ depending on sex, body composition, and parental country of birth?

BMC Public Health. 2022 Oct 11;22(1):1895. doi: 10.1186/s12889-022-14297-0.

ABSTRACT

BACKGROUND: Adolescents and young adults around the world experience high rates of weight gain. The underlying eating behaviours that may lead to overconsumption of energy are complex and can depend on a number of factors. The aim of this study was to explore if eating behaviour among adolescents and young adults referred to specialized obesity treatment differed depending on sex, body composition, and parental country of birth.

METHODS: Adolescents and young adults aged 16-25 years, referred for obesity treatment in 2018-2021 were included in the study. Eating behaviour was assessed using the Three Factor Eating Questionnaire, comprising domains of uncontrolled-, emotional- and cognitive restraint eating. Student’s t-test was used to compare differences in eating behaviour scores between males and females, and between those having at least one parent born in a Nordic country and those with both parents born outside the Nordic countries. Associations between BMI, waist circumference, and body fat percentage, and eating behaviour as the dependent variable, were examined using linear regression.

RESULTS: A total of 463 participants, mean age 21 years and mean BMI 41.3 kg/m2, were included in the analysis. Females scored statistically significantly higher than males on emotional eating (45.8 vs. 35.4, p = 0.002) and cognitive restraint eating (45.4 vs. 39.2, p = 0.009). Participants with at least one parent born in a Nordic country reported a statistically significantly lower score of uncontrolled eating (45.7 vs. 51.3, p = 0.02) compared to participants with both parents born outside the Nordic countries. Further, there were statistically significant inverse associations between cognitive restraint eating scores and BMI (β=-0.64, 95%CI: -0.97 to -0.31), waist circumference (β=-0.44, 95%CI: -0.61 to -0.27) and body fat percentage (β=-0.57, 95%CI: -1.01 to -0.14) in models adjusted for age, sex, smoking, and civil status.

CONCLUSION: Our findings suggest that sex and parental country of birth may influence eating behaviours among adolescents and young adults referred for specialist obesity treatment. We also found that cognitive restraint eating decreased with increasing BMI, waist circumference, and body fat percentage. This indicates that there may be an inverse association between the ability to restrain oneself from eating and gaining weight, however, the direction of the association must be investigated further. Increased knowledge about eating behaviours may be valuable in the clinical setting.

PMID:36221108 | DOI:10.1186/s12889-022-14297-0

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Nevin Manimala Statistics

Self-referrals and associated factors among laboring mothers at Dilla University Referral Hospital, Dilla, Gedeo Zone, Ethiopia: a cross-sectional study

BMC Womens Health. 2022 Oct 11;22(1):417. doi: 10.1186/s12905-022-02002-7.

ABSTRACT

BACKGROUND: When medical cases are difficult to manage at the level of primary health care units (PHCU), formal referral assists patients transferring to a higher level of care. In contrast, self-referral and bypassing are synonymously used in literature to describe the phenomenon of patients skipping their units to get basic medical services, even though they are close to their residence. Though proper and timely referral prevents the majority of deaths from obstetric complications in developing countries, more than 50% of referrals are self-referral trends. Such patient practice is increasingly becoming a concern for many health-care systems.

OBJECTIVE: To assess the magnitude of self-referrals and associated factors among laboring mothers at Gedeo Zone, Ethiopia.

METHODS: Facility-based cross-sectional study was conducted from August 1-September 30/2021 among laboring mothers at Dilla University Referral Hospital. A systematic random sampling technique was used to select 375 laboring mothers. Data were collected using a face-to-face interview with a structured questionnaire. Data were entered into a computer using Epi-Data 4.6 statistical program and then exported to STATA version 16 for analysis. In bivariate analysis variables with a p-value ≤ 0.25 were selected as a candidate variable for the multivariable analysis. P-value < 0.05 at 95% confidence interval considered as a statistically significant associations in the multivariable analysis.

RESULT: 375 eligible mothers participated in the study, with a response rate of 98.16%. The magnitude of self-referrals among laboring mothers was 246 (65.6%) with 95% CI (0.60-0.70). Time ≥ 30 min to reach nearby facilities (AOR = 1.74, 95% CI, 1.08, 2.81), having no medicine supplies at nearby facilities (AOR = 1.75, 95% CI, 1.08, 2.82), having no equipment and supplies at nearby facilities (AOR = 1.70, 95% CI, 1.03, 2.78), having ANC visits ˃ 3 times (AOR = 0.29, 95% CI, 0.15, 0.55) and having poor perception of health provider technical competence at nearby facilities (AOR = 2.97, 95% CI, 1.83, 4.79) were found as significant factors for self-referral.

CONCLUSION: The magnitude of self-referral was high. Frequent Antenatal visits were protective, however time to reach the nearest facilities, perception towards health care providers, medicine, equipment and supplies at the nearest facilities were positive influencing factors. Government stakeholders should keep working on improving the quality of health service, especially at primary health care units(PHCU).

PMID:36221100 | DOI:10.1186/s12905-022-02002-7

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The effect of neuromuscular electrical stimulation on serum glucose levels in children and adolescents with type-1 diabetes mellitus: a single group clinical trial

BMC Endocr Disord. 2022 Oct 11;22(1):246. doi: 10.1186/s12902-022-01149-6.

ABSTRACT

BACKGROUND: This study aimed to evaluate the effect of Neuromuscular Electrical Stimulation (NMES) on serum glucose level in children and adolescents with type-1 diabetes.

METHODS: This before-after, single-group, clinical trial was conducted on 29 patients with type-1 diabetes mellitus with the age range of 7-18 years. The patients underwent NMES in two 20-minute phases on the quadriceps and hamstrings muscles, three sessions per week for a period of 8 weeks. Fasting Blood Sugar (FBS), measured in two ways, by glucometer and laboratory testing, was considered as the primary outcome and the glycated hemoglobin (HbA1c) and the total daily dose (TDD) of insulin were measured as the secondary outcomes. The laboratory FBS and HbA1c were measured 1 day before the intervention (as a baseline value) and then 2 and 6 weeks after the last session of intervention. FBS by glucometer and total daily dose of insulin were recorded daily from 2 weeks before the intervention to the last day of the intervention and consequently, the weekly average of these variables was calculated and used for statistical analysis.

RESULTS: The serum level of FBS (measured by glucometer) and the total daily dose of insulin reduced significantly 2 weeks after beginning of intervention. The laboratory serum level of FBS decreased significantly in the second week after the end of intervention compared to the baseline values. Although the HbA1c level decreased at follow-up period (2 and 6 weeks after the intervention), it was not significant.

CONCLUSION: It seems that 8 weeks of NMES has beneficial effects on the reduction of FBS and TDD of insulin therefore, it could be suggested as the contributory treatment in management of children and adolescents with type-1 diabetes.

TRIAL REGISTRATION: The study was registered at https://fa.irct.ir/user/trial/51739/view (IRCT20100523003998N1) in date of 25/10/2020.

PMID:36221091 | DOI:10.1186/s12902-022-01149-6

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Nevin Manimala Statistics

Prevalence of sexual harassment among young Spaniards before, during, and after the COVID-19 lockdown period in Spain

BMC Public Health. 2022 Oct 11;22(1):1888. doi: 10.1186/s12889-022-14264-9.

ABSTRACT

BACKGROUND: Sexual harassment is a type of coercion, including social pressure, intimidation, physical force, and verbal acts, in addition to other forms such as cyber-harassment, recognized as a major important public health problem.

METHODS: This cross-sectional study, based on a survey administered online to men and women aged 18 to 35 years and living in Spain throughout 15th and 28th October 2020, aims to analyze the prevalence and factors associated with sexual harassment among young people in Spain within the last 12 months, particularly according to the COVID-19 lockdown period. It has been conducted by bivariate analysis and robust Poisson regression models. The final sample includes 2.515 participants.

RESULTS: The results indicate that women were almost twice as likely as men to experience sexual harassment (49% vs 22.2%). Also, among heterosexual men and women, the estimated prevalence was lower concerning that observed among bisexuals, gays, and lesbians (31.5% vs 53, 39.2, and 34.6% respectively). The prevalence percentage in the 18-24 age group was twice high as that observed in the 30-35 age group. Finally, during the lockdown period, the harassment through electronic channels increased (32.6% vs 16.5 and 17.8% before and after this period, respectively) and decreased on public roads (22.9% vs 63.4 and 54.4% pre-lockdown and post-lockdown periods, respectively).

CONCLUSION: These findings highlight that sexual harassment presents a high prevalence among young people, especially cyber-harassment, and workplace harassment and it is important to be aware that young women are more likely to suffer harassment and even more if they do not have a partner or have LGB orientation. During the lockdown sexual harassment has moved from public spaces to the social network.

PMID:36221078 | DOI:10.1186/s12889-022-14264-9

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Nevin Manimala Statistics

Association between triglyceride glucose index and atherosclerotic plaques and Burden: findings from a community-based study

Cardiovasc Diabetol. 2022 Oct 11;21(1):204. doi: 10.1186/s12933-022-01638-x.

ABSTRACT

BACKGROUND: Insulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR).

METHODS: Participants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively.

RESULTS: Among 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P < 0.05). However, the association between HOMA-IR and intracranial atherosclerosis was not statistically significant after adjustment for all potential confounders. Discordantly high TyG index with HOMA-IR had a higher odd of extracranial plaque (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.04-1.71), extracranial atherosclerotic burden (common odds ratio [cOR]: 1.35, 95% CI 1.06-1.71), coronary plaque (OR: 1.30, 95% CI 1.01-1.68) and segment stenosis score (cOR: 1.39, 95% CI 1.09-1.78) as compared with concordantly low TyG index with HOMA-IR. The TyG index had a better net reclassification improvement ability than HOMA-IR for atherosclerotic plaques when adding to baseline model.

CONCLUSION: Elevated TyG index was associated with increased odds of atherosclerosis in coronary/intra- and extracranial arteries. Compared with HOMA-IR, the TyG index was more strongly associated with intracranial atherosclerosis. Moreover, discordantly high TyG index with HOMA-IR was also important for atherosclerosis identification.

PMID:36221073 | DOI:10.1186/s12933-022-01638-x

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Nevin Manimala Statistics

Deep learning algorithm reveals two prognostic subtypes in patients with gliomas

BMC Bioinformatics. 2022 Oct 11;23(1):417. doi: 10.1186/s12859-022-04970-x.

ABSTRACT

BACKGROUND: Gliomas are highly complex and heterogeneous tumors, rendering prognosis prediction challenging. The advent of deep learning algorithms and the accessibility of multi-omic data represent a new approach for the identification of survival-sensitive subtypes. Herein, an autoencoder-based approach was used to identify two survival-sensitive subtypes using RNA sequencing (RNA-seq) and DNA methylation (DNAm) data from The Cancer Genome Atlas (TCGA) dataset. The subtypes were used as labels to build a support vector machine model with cross-validation. We validated the robustness of the model on Chinese Glioma Genome Atlas (CGGA) dataset. DNAm-driven genes were identified by integrating DNAm and gene expression profiling analyses using the R MethylMix package and carried out for further enrichment analysis.

RESULTS: For TCGA dataset, the model produced a high C-index (0.92 ± 0.02), low brier score (0.16 ± 0.02), and significant log-rank p value (p < 0.0001). The model also had a decent performance for CGGA dataset (CGGA DNAm: C-index of 0.70, brier score of 0.21; CGGA RNA-seq: C-index of 0.79, brier score of 0.18). Moreover, we identified 389 DNAm-driven genes of survival-sensitive subtypes, which were significantly enriched in the glutathione metabolism pathway.

CONCLUSIONS: Our study identified two survival-sensitive subtypes of glioma and provided insights into the molecular mechanisms underlying glioma development; thus, potentially providing a new target for the prognostic prediction of gliomas and supporting personalized treatment strategies.

PMID:36221066 | DOI:10.1186/s12859-022-04970-x