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Nevin Manimala Statistics

Comparison of three statistical approaches for feature selection for fine-scale genetic population assignment in four pig breeds

Trop Anim Health Prod. 2021 Jul 10;53(3):395. doi: 10.1007/s11250-021-02824-x.

ABSTRACT

BACKGROUND: Assigning animals to their corresponding breeds through breed informative single-nucleotide polymorphisms (SNPs) is required in many fields. For instance, it is used in the traceability and the authentication of meat and other livestock products. SNPs’ information for several pork breeds are now accessible thanks to the availability of dense SNP chips. These SNP chips cover a large number of molecular markers distributed across the entire genome. To identify the pork breed from a sample of industrial meat, one must analyze a large panel of genetic markers depending on the SNP chip used. The analysis of such large datasets requires intensive work. This leads to the idea of creating less dense chips of breed informative markers based on a reduced number of SNPs. Therefore, the analysis of the data emanating from the genotyping of these reduced chips will require less time and effort.

AIM: The objective of this study is to find the most informative SNPs for the discrimination between four pig breeds, namely Duroc, Landrace, Large White, and Pietrain.

METHOD: The Illumina Porcine 60 k SNP chip was used to genotype SNPs distributed all over the individuals’ genomes. Firstly, we used three different statistical approaches for feature selection: (i) principal component analysis (PCA), (ii) least absolute shrinkage and selection operator (LASSO), and (iii) random forest (RF). These three approaches identified three sets of SNPs; each set corresponds to one approach. Then, we combined the results of the three methods by setting up a final panel containing the SNPs which appear on the three sets altogether.

RESULTS: Separately, each method resulted in a panel with the corresponding most discriminating SNPs. The PCA, the LASSO, and the random forest with Boruta algorithm highlighted 28,816, 50, and 286 SNPs, respectively. The number of SNPs selected by PCA is high compared to Boruta and LASSO because PCA chooses the variables while preserving as much information about the data as possible. The only downside of LASSO regression is that among a group of correlated variables, LASSO tends to select only one variable and ignore the others regardless of their importance. Contrarily to LASSO, the Boruta algorithm considers the interdependence between SNPs and selects informative variables even if they are correlated and have the same effect. The three panels shared 23 SNPs; the distribution of the individuals according to these SNPs showed a grouping of individuals of each breed in well-defined clusters without any overlapping.

CONCLUSIONS: The biological pathways represented by 23 breed informative SNPs resulted by the combination of PCA, LASSO, and Boruta should be explored in further analysis. The results provided by our study are promising for further applications of this method in other livestock animals.

PMID:34245361 | DOI:10.1007/s11250-021-02824-x

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Nevin Manimala Statistics

Impact of Advancing Age on the Status and Risk of Postoperative Infections After Liver Resection

World J Surg. 2021 Jul 9. doi: 10.1007/s00268-021-06236-8. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status.

METHODS: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively).

RESULTS: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29).

CONCLUSIONS: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.

PMID:34244815 | DOI:10.1007/s00268-021-06236-8

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Nevin Manimala Statistics

Choroidal vascular structures in diabetic patients: a meta-analysis

Graefes Arch Clin Exp Ophthalmol. 2021 Jul 10. doi: 10.1007/s00417-021-05292-z. Online ahead of print.

ABSTRACT

PURPOSE: Choroidal vascular structures are likely to be affected in diabetic patients. The aim of this study was to conduct a meta-analysis of choroidal vascular structures in diabetic eyes with no diabetic retinopathy (NDR) and healthy control eyes, which was systematically evaluated by various factors involving the measurements.

METHODS: This study identified clinical data from publications in PubMed and web of science until May 2020. Independent retrospective or prospective clinical studies comparing NDR and healthy control eyes regarding choroidal vascular structures were extracted. Five related studies were enrolled, cumulating in a total of 282 diabetic eyes and 511 control eyes examined in this study. Heterogeneity was statistically quantified by I2 statistics, and meta-analysis was performed using a random effects model. This study included 2 different algorisms of binarization determining the ratio of luminal areas in total choroidal areas, both of which were consolidated and called “choroidal vascular ratio.”

RESULTS: Meta-analysis clearly showed that the choroidal vascular ratio was significantly lower in NDR eyes than in healthy control eyes (weighted mean difference = – 2.16; 95%CI: – 3.19 to – 1.13; P < 0.005). Similar results were obtained in sub-analysis based on adjustment of serum HbA1c levels and duration of diabetes.

CONCLUSIONS: The choroidal vascular ratio of NDR eyes was significantly lower than that of healthy control eyes. The ratio might contribute to a better understanding of the pathophysiology involved in the development of diabetic retinopathy, although there was some heterogeneity in primary analysis studies.

PMID:34244824 | DOI:10.1007/s00417-021-05292-z

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Nevin Manimala Statistics

Femoral Nerve Blockade Does Not Lead to Subjective Functional Deficits After Anterior Cruciate Ligament Reconstruction

Mil Med. 2021 Jul 9:usab269. doi: 10.1093/milmed/usab269. Online ahead of print.

ABSTRACT

INTRODUCTION: Anterior cruciate ligament reconstruction (ACLR) ranks among the most common surgeries performed in civilian as well as military orthopedic settings. Regional anesthesia, and the femoral nerve block (FNB) in particular, has demonstrated efficacy in reducing postoperative pain and opioid use after ACLR, however concerns linger about possible impaired functional outcomes. The purpose of the current investigation was to assess International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) scores at 6 to 12 months after ACLR in patients who did (FNB) and did not (NoFNB) receive a perioperative FNB.

MATERIALS AND METHODS: All patients undergoing unilateral ACLR in the study period were reviewed in this institutional process improvement analysis. The primary outcome was prospectively collected IKDC-SKF scores obtained at 6-12 months post-surgery. Demographic and surgical information collected as potential covariates included age, sex, body mass index (BMI), preoperative IKDC-SKF score, use of an FNB, use of another (not femoral nerve) block, American Society of Anesthesiologists (ASA) score, graft type (auto vs. allograft), concomitant meniscus or cartilage procedures, tobacco use, tourniquet time, and primary vs. revision surgery. Assuming a 1:2 ratio of patients who did not vs. did receive FNBs and a clinically meaningful difference of 7 points on the IKDC-SKF, 112 patients were required for 80% power. A regression model averaging approach examined the relationships between covariates and postoperative IKDC-SKF scores.

RESULTS: One hundred nineteen patients met inclusion criteria (FNB 79 and NoFNB 40). The cohorts were significantly different in several factors including BMI, ASA level, graft type, and other peripheral nerve blocks, which were controlled for through regression modeling. Regressions with model averaging examined the relationship between treatment groups and postoperative IKDC-SKF scores, along with other potential predictor variables. Estimated adjusted marginal differences in postoperative IKDC-SKF scores from the best-fitting model revealed a very small 0.66-point mean (P = .86) difference between NoFNB and FNB groups that was not statistically significant. Those who reported tobacco use had a 10.51 point (P = .008) lower mean postoperative IKDC-SKF score than those who did not report tobacco use. Every 1-point increase in the preoperative IKDC-SKF score was associated with a 0.28-point (P = .02) increase in the postsurgical IKDC-SKF score.

CONCLUSIONS: Active tobacco use may negatively impact short-term subjective patient-reported outcomes after ACLR, as reported by the IKDC-SKF. Lower preoperative scores are also associated with significantly lower postoperative IKDC-SKF scores while the use of a FNB was not associated with lower postoperative scores. The negative association between tobacco use and patient-reported functional outcomes after ACLR lends further support to tobacco cessation programs within the military.

PMID:34244804 | DOI:10.1093/milmed/usab269

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Nevin Manimala Statistics

Inferring single cell expression profiles from overlapped pooling sequencing data with compressed sensing strategy

Nucleic Acids Res. 2021 Jul 9:gkab581. doi: 10.1093/nar/gkab581. Online ahead of print.

ABSTRACT

Though single cell RNA sequencing (scRNA-seq) technologies have been well developed, the acquisition of large-scale single cell expression data may still lead to high costs. Single cell expression profile has its inherent sparse properties, which makes it compressible, thus providing opportunities for solutions. Here, by computational simulation as well as experiment of 54 single cells, we propose that expression profiles can be compressed from the dimension of samples by overlapped assigning each cell into plenty of pools. And we prove that expression profiles can be inferred from these pool expression data with overlapped pooling design and compressed sensing strategy. We also show that by combining this approach with plate-based scRNA-seq measurement, it can maintain its superiorities in gene detection sensitivity and individual identity and recover the expression profile with high precision, while saving about half of the library cost. This method can inspire novel conceptions on the measurement, storage or computation improvements for other compressible signals in many biological areas.

PMID:34244789 | DOI:10.1093/nar/gkab581

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Nevin Manimala Statistics

Cognitive Load Impairs Time to Initiate and Complete Shooting Tasks in ROTC Members

Mil Med. 2021 Jul 9:usab276. doi: 10.1093/milmed/usab276. Online ahead of print.

ABSTRACT

INTRODUCTION: Multitasking typically requires an individual to simultaneously process cognitive information while performing a motor task. Cognitive motor interference (CMi) is encountered when cognitive challenges negatively impact motor task performance. Military personnel encounter cognitively taxing situations, especially during combat or other tactical performance scenarios, which may lead to injury or motor performance deficits (i.e., shooting inaccuracy, delayed stimulus-response time, and slowed movement speed). The purpose of the current study was to develop four cognitive motor shooting paradigms to determine the effects of cognitive load on shooting performance in healthy Reserve Officers’ Training Corps (ROTC) cadets.

METHODS: Thirty-two healthy collegiate ROTC members (24 male and 8 female; 20.47 ± 1.24 years, 174.95 ± 10.58 cm, and 77.99 ± 13.90 kg) were recruited to complete four simulated shooting tasks with additional “motor” challenge (180° turn, gait, weighted, and unweighted landing) and with and without a “cognitive” decision-making challenge requiring response selection and inhibition to both auditory and visual stimuli, totaling eight multi-task cognitive motor shooting conditions. The current study was approved by the university’s Institutional Review Board. Task initiation (seconds), task completion (seconds), and number of misses were calculated to determine marksmanship efficiency and accuracy. For each task, a multivariate repeated-measures analysis of variance (ANOVA) was conducted for the combined dependent variables. If the overall multivariate repeated-measures ANOVA was significant, follow-up univariate ANOVAs were conducted for each dependent variable. Alpha was set at α = 0.05 for all analyses.

RESULTS: Task initiation increased for the cognitive condition for the 180° turn (4.29 ± 1.22 seconds baseline, 5.09 ± 1.39 seconds cognitive; P < .05), gait (2.76 ± .60 seconds baseline, 3.93 ± .62 seconds cognitive; P < .05), unweighted (1.27 ± .57 seconds baseline, 3.39 ± .63 seconds cognitive; P < .05), and weighted landing (1.46 ± .72 seconds baseline, 3.35 ± .60 seconds cognitive; P < .05). Task completion time increased for the cognitive condition for the 180° turn (3.48 ± 1.53 seconds baseline, 4.85 ± 1.24 seconds cognitive; P < .05), gait (7.84 ± 2.07 seconds baseline, 9.23 ± 1.76 seconds cognitive; P < .05), unweighted (5.98 ± 1.55 seconds baseline, 7.45 ± 1.51 seconds cognitive; P < .05), and weighted landing (6.09 ± 1.42 seconds baseline, 7.25 ± 1.79 seconds cognitive; P < .05). There were no statistically significant differences in the number of misses for any of the tasks between conditions (P > .05).

CONCLUSIONS: The addition of a cognitive load increased both task initiation and task completion times during cognitive motor simulated shooting. Adding cognitive loads to tactical performance tasks can result in CMi and negatively impact tactical performance. Thus, consideration for additional cognitive challenges into training may be warranted to reduce the potential CMi effect on tactical performance.

PMID:34244784 | DOI:10.1093/milmed/usab276

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Nevin Manimala Statistics

Predicting and forecasting the impact of local outbreaks of COVID-19: use of SEIR-D quantitative epidemiological modelling for healthcare demand and capacity

Int J Epidemiol. 2021 Jul 9:dyab106. doi: 10.1093/ije/dyab106. Online ahead of print.

ABSTRACT

BACKGROUND: The world is experiencing local/regional hotspots and spikes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. We aimed to formulate an applicable epidemiological model to accurately predict and forecast the impact of local outbreaks of COVID-19 to guide the local healthcare demand and capacity, policy-making and public health decisions.

METHODS: The model utilized the aggregated daily COVID-19 situation reports (including counts of daily admissions, discharges and bed occupancy) from the local National Health Service (NHS) hospitals and COVID-19-related weekly deaths in hospitals and other settings in Sussex (population 1.7 million), Southeast England. These data sets corresponded to the first wave of COVID-19 infections from 24 March to 15 June 2020. A novel epidemiological predictive and forecasting model was then derived based on the local/regional surveillance data. Through a rigorous inverse parameter inference approach, the model parameters were estimated by fitting the model to the data in an optimal sense and then subsequent validation.

RESULTS: The inferred parameters were physically reasonable and matched up to the widely used parameter values derived from the national data sets by Biggerstaff M, Cowling BJ, Cucunubá ZM et al. (Early insights from statistical and mathematical modeling of key epidemiologic parameters of COVID-19, Emerging infectious diseases. 2020;26(11)). We validate the predictive power of our model by using a subset of the available data and comparing the model predictions for the next 10, 20 and 30 days. The model exhibits a high accuracy in the prediction, even when using only as few as 20 data points for the fitting.

CONCLUSIONS: We have demonstrated that by using local/regional data, our predictive and forecasting model can be utilized to guide the local healthcare demand and capacity, policy-making and public health decisions to mitigate the impact of COVID-19 on the local population. Understanding how future COVID-19 spikes/waves could possibly affect the regional populations empowers us to ensure the timely commissioning and organization of services. The flexibility of timings in the model, in combination with other early-warning systems, produces a time frame for these services to prepare and isolate capacity for likely and potential demand within regional hospitals. The model also allows local authorities to plan potential mortuary capacity and understand the burden on crematoria and burial services. The model algorithms have been integrated into a web-based multi-institutional toolkit, which can be used by NHS hospitals, local authorities and public health departments in other regions of the UK and elsewhere. The parameters, which are locally informed, form the basis of predicting and forecasting exercises accounting for different scenarios and impacts of COVID-19 transmission.

PMID:34244764 | DOI:10.1093/ije/dyab106

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Nevin Manimala Statistics

Free the Bun: Prevalence of Alopecia Among Active Duty Service Women, Fiscal Years 2010-2019

Mil Med. 2021 Jul 9:usab274. doi: 10.1093/milmed/usab274. Online ahead of print.

ABSTRACT

INTRODUCTION: Active duty service women (ADSW) constitute 16% of the force. The prevalence of alopecia, a dermatologic condition characterized by hair loss, is understudied in regard to hairstyle regulations across the U.S. military services. Alopecia has several causes; one of which is due to tension on the scalp secondary to tight hairstyles. In the U.S., alopecia has a lifetime prevalence of 1.7-2.1%; no previous studies which evaluated this condition in service women were found.

MATERIALS AND METHODS: We used the Military Health System Data Repository to perform a retrospective study to assess the prevalence of alopecia in ADSW from fiscal years (FYs) 2010 to 2019. Statistical analyses included descriptive statistics on patient demographics and trend analysis on the prevalence of alopecia over the 10-year study period.

RESULTS: A total of 498,219 ADSW were identified over the 10-year study period, of which 2.40% had a diagnosis of alopecia. Overall, the prevalence of alopecia decreases over the 10-year period, with two observed periods of slight increase (FY 2013 to 2014 and FY 2018 to 2019) when comparing prevalence year-to-year. Of those diagnosed, the majority were young, Black, with a senior enlisted rank, and in the U.S. Army.

CONCLUSION: The prevalence of alopecia in ADSW is slightly higher than that in civilian populations and is most likely underreported. It is more commonly diagnosed in Black women than would be expected based on ratios of this population in military service. Policy changes to ensure that traction alopecia is a qualifying medical condition for Veterans Affairs disability compensation, mechanisms are in place for more specific coding in the electronic medical record, and treatment options to be covered by TRICARE are recommended. All U.S. military services should consider updating and evaluating regulations to improve the health and quality of life of ADSW.

PMID:34244770 | DOI:10.1093/milmed/usab274

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PseudoGA: cell pseudotime reconstruction based on genetic algorithm

Nucleic Acids Res. 2021 Jul 9:gkab457. doi: 10.1093/nar/gkab457. Online ahead of print.

ABSTRACT

Dynamic regulation of gene expression is often governed by progression through transient cell states. Bulk RNA-seq analysis can only detect average change in expression levels and is unable to identify this dynamics. Single cell RNA-seq presents an unprecedented opportunity that helps in placing the cells on a hypothetical time trajectory that reflects gradual transition of their transcriptomes. This continuum trajectory or ‘pseudotime’, may reveal the developmental pathway and provide us with information on dynamic transcriptomic changes and other biological processes. Existing approaches to build pseudotime heavily depend on reducing huge dimension to extremely low dimensional subspaces and may lead to loss of information. We propose PseudoGA, a genetic algorithm based approach to order cells assuming that gene expressions vary according to a smooth curve along the pseudotime trajectory. We observe superior accuracy of our method in simulated as well as benchmarking real datasets. Generality of the assumption behind PseudoGA and no dependence on dimensionality reduction technique make it a robust choice for pseudotime estimation from single cell transcriptome data. PseudoGA is also time efficient when applied to a large single cell RNA-seq data and adaptable to parallel computing. R code for PseudoGA is freely available at https://github.com/indranillab/pseudoga.

PMID:34244782 | DOI:10.1093/nar/gkab457

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Tutorial: best practices and considerations for mass-spectrometry-based protein biomarker discovery and validation

Nat Protoc. 2021 Jul 9. doi: 10.1038/s41596-021-00566-6. Online ahead of print.

ABSTRACT

Mass-spectrometry-based proteomic analysis is a powerful approach for discovering new disease biomarkers. However, certain critical steps of study design such as cohort selection, evaluation of statistical power, sample blinding and randomization, and sample/data quality control are often neglected or underappreciated during experimental design and execution. This tutorial discusses important steps for designing and implementing a liquid-chromatography-mass-spectrometry-based biomarker discovery study. We describe the rationale, considerations and possible failures in each step of such studies, including experimental design, sample collection and processing, and data collection. We also provide guidance for major steps of data processing and final statistical analysis for meaningful biological interpretations along with highlights of several successful biomarker studies. The provided guidelines from study design to implementation to data interpretation serve as a reference for improving rigor and reproducibility of biomarker development studies.

PMID:34244696 | DOI:10.1038/s41596-021-00566-6