Category: Statistics

AIDS. 2023 Jul 7. doi: 10.1097/QAD.0000000000003646. Online ahead of print.

ABSTRACT

OBJECTIVE: Viral failure in people living with HIV (PLWH) may be influenced by multiple socio-behavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries.

DESIGN: Cohort study.

METHODS: The African Cohort Study is an ongoing, longitudinal cohort enrolling PLWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, socio-behavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load ≥1000 copies/mL among participants on antiretroviral therapy (ART) for at least six months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered.

RESULTS: Between January 2013 and December 2020, 2,941 PLWH were enrolled, 1,602 had been on ART for at least 6 months, and 1,571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PLWH with viral failure (AUC: 0.82 vs 0.75). Both models identified CD4 count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure.

CONCLUSION: These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.

PMID:37418549 | DOI:10.1097/QAD.0000000000003646

PLoS Genet. 2023 Jul 7;19(7):e1010539. doi: 10.1371/journal.pgen.1010539. Online ahead of print.

ABSTRACT

Predicting phenotypes from genotypes is a fundamental task in quantitative genetics. With technological advances, it is now possible to measure multiple phenotypes in large samples. Multiple phenotypes can share their genetic component; therefore, modeling these phenotypes jointly may improve prediction accuracy by leveraging effects that are shared across phenotypes. However, effects can be shared across phenotypes in a variety of ways, so computationally efficient statistical methods are needed that can accurately and flexibly capture patterns of effect sharing. Here, we describe new Bayesian multivariate, multiple regression methods that, by using flexible priors, are able to model and adapt to different patterns of effect sharing and specificity across phenotypes. Simulation results show that these new methods are fast and improve prediction accuracy compared with existing methods in a wide range of settings where effects are shared. Further, in settings where effects are not shared, our methods still perform competitively with state-of-the-art methods. In real data analyses of expression data in the Genotype Tissue Expression (GTEx) project, our methods improve prediction performance on average for all tissues, with the greatest gains in tissues where effects are strongly shared, and in the tissues with smaller sample sizes. While we use gene expression prediction to illustrate our methods, the methods are generally applicable to any multi-phenotype applications, including prediction of polygenic scores and breeding values. Thus, our methods have the potential to provide improvements across fields and organisms.

PMID:37418505 | DOI:10.1371/journal.pgen.1010539

PLoS One. 2023 Jul 7;18(7):e0288335. doi: 10.1371/journal.pone.0288335. eCollection 2023.

ABSTRACT

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world’s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the “Medicines for Malaria Venture” organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds’ ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.

PMID:37418497 | DOI:10.1371/journal.pone.0288335

PLoS Genet. 2023 Jul 7;19(7):e1010807. doi: 10.1371/journal.pgen.1010807. Online ahead of print.

ABSTRACT

Germline mutation is the mechanism by which genetic variation in a population is created. Inferences derived from mutation rate models are fundamental to many population genetics inference methods. Previous models have demonstrated that nucleotides flanking polymorphic sites-the local sequence context-explain variation in the probability that a site is polymorphic. However, limitations to these models exist as the size of the local sequence context window expands. These include a lack of robustness to data sparsity at typical sample sizes, lack of regularization to generate parsimonious models and lack of quantified uncertainty in estimated rates to facilitate comparison between models. To address these limitations, we developed Baymer, a regularized Bayesian hierarchical tree model that captures the heterogeneous effect of sequence contexts on polymorphism probabilities. Baymer implements an adaptive Metropolis-within-Gibbs Markov Chain Monte Carlo sampling scheme to estimate the posterior distributions of sequence-context based probabilities that a site is polymorphic. We show that Baymer accurately infers polymorphism probabilities and well-calibrated posterior distributions, robustly handles data sparsity, appropriately regularizes to return parsimonious models, and scales computationally at least up to 9-mer context windows. We demonstrate application of Baymer in three ways-first, identifying differences in polymorphism probabilities between continental populations in the 1000 Genomes Phase 3 dataset, second, in a sparse data setting to examine the use of polymorphism models as a proxy for de novo mutation probabilities as a function of variant age, sequence context window size, and demographic history, and third, comparing model concordance between different great ape species. We find a shared context-dependent mutation rate architecture underlying our models, enabling a transfer-learning inspired strategy for modeling germline mutations. In summary, Baymer is an accurate polymorphism probability estimation algorithm that automatically adapts to data sparsity at different sequence context levels, thereby making efficient use of the available data.

PMID:37418489 | DOI:10.1371/journal.pgen.1010807

PLoS One. 2023 Jul 7;18(7):e0288227. doi: 10.1371/journal.pone.0288227. eCollection 2023.

ABSTRACT

This study investigated the relationship between psychological skills and fitness levels among elite taekwondo athletes. A total of ten Iranian male elite taekwondo athletes (mean age of 20.6±2 years, BMI 18.78±0.62 kg/m2, and fat percentage of 8.87±1.46%) participated in the study. The Sports Emotional Intelligence Questionnaire, Sports Success Scale, Sport Mental Toughness Questionnaire, and Mindfulness Inventory for Sport were used to assess psychological factors. The Wingate test was used to determine anaerobic power, and the Bruce test to determine aerobic fitness. Descriptive statistics and Spearman rank correlation coefficients were utilised to examine any relationships between subscales. Statistically significant correlations were recorded between the evaluation of feelings (EI scale) and VO2peak (ml/kg/min) (r = -0.70, p = 0.0235) and between social skills (EI scale) and relative peak power (W/kg) (r = 0.84, p = 0.0026). Also, between optimism (EI scale) and VO2peak (ml/kg/min) (r = -0.70, p = 0.0252) and between optimism (EI scale) and HR-MAX (r = -0.75, p = 0.0123); and, finally, between control (mental toughness scale) and relative peak power (W/kg) (r = 0.67, p = 0.0360). These findings demonstrate relationships between psychological factors and the advantages of good anaerobic and aerobic capabilities. Finally, the study also demonstrated that elite taekwondo athletes have high mental performance abilities that are interrelated with anaerobic and aerobic performance.

PMID:37418479 | DOI:10.1371/journal.pone.0288227

Med Phys. 2023 Jul 7. doi: 10.1002/mp.16578. Online ahead of print.

ABSTRACT

BACKGROUND: Accuracy of electrode placement for deep brain stimulation (DBS) is critical to achieving desired surgical outcomes and impacts the efficacy of treating neurodegenerative diseases. Intraoperative brain shift degrades the accuracy of surgical navigation based on preoperative images.

PURPOSE: We extended a model-based image updating scheme to address intraoperative brain shift in DBS surgery and improved its accuracy in deep brain.

METHODS: We evaluated 10 patients, retrospectively, who underwent bilateral DBS surgery and classified them into groups of large and small deformation based on a 2 mm subsurface movement threshold and brain shift index of 5%. In each case, sparse brain deformation data were used to estimate whole brain displacements and deform preoperative CT (preCT) to generate updated CT (uCT). Accuracy of uCT was assessed using target registration errors (TREs) at the Anterior Commissure (AC), Posterior Commissure (PC), and four calcification points in the sub-ventricular area by comparing their locations in uCT with their ground truth counterparts in postoperative CT (postCT).

RESULTS: In the large deformation group, TREs were reduced from 2.5 mm in preCT to 1.2 mm in uCT (53% compensation); in the small deformation group, errors were reduced from 1.25 to 0.74 mm (41%). Average reduction of TREs at AC, PC and pineal gland were significant, statistically (p ⩽ 0.01).

CONCLUSIONS: With more rigorous validation of model results, this study confirms the feasibility of improving the accuracy of model-based image updating in compensating for intraoperative brain shift during DBS procedures by assimilating deep brain sparse data.

PMID:37418478 | DOI:10.1002/mp.16578

PLoS One. 2023 Jul 7;18(7):e0288323. doi: 10.1371/journal.pone.0288323. eCollection 2023.

ABSTRACT

Concerns over food safety issues during the coronavirus pandemic (COVID-19) have sparked worldwide interest. Being part of a farm-to-fork food safety chain, food handlers at home are the final line of defense in reducing foodborne diseases. The present study used a cross-sectional survey to investigate the knowledge, attitudes, and practices (KAP) of women food handlers in Jordan. The survey investigated the effect of the COVID-19 pandemic on women who handle food at home in terms of food safety KAP. One thousand one hundred twenty-six respondents completed a food safety questionnaire during the COVID-19 pandemic. With a mean score of 22.1 points out of 42, the results showed that women who handle food in their houses had insufficient knowledge, negative attitudes, and incorrect practices concerning food safety. The respondents demonstrated high knowledge, attitudes, and practices in the personal hygiene, cleaning and sanitation areas (≥ 60.0%). On the other hand, participants’ knowledge, attitudes, and practices regarding contamination prevention, health issues that would affect food safety, symptoms of foodborne illnesses, safe storage, thawing, cooking, keeping, and reheating of foods, as well as COVID-19 were all low (< 60.0%). The correlations between participants’ total food safety KAP scores and education, age, experience, region, and the pandemic effect on food safety were statistically significant (P ≤ 0.05). To the best of our knowledge, this study is the first conducted in Jordan to investigate food safety knowledge, attitudes, and practices by women handling food at home during the COVID-19 pandemic.

PMID:37418464 | DOI:10.1371/journal.pone.0288323

PLoS One. 2023 Jul 7;18(7):e0288020. doi: 10.1371/journal.pone.0288020. eCollection 2023.

ABSTRACT

BACKGROUND: People with chronic diseases in their advanced phase require palliative care. This is essential to ensure their quality of life as it ends. However, a very low percentage of patients receive the necessary palliative care. The COVID-19 pandemic has adversely affected the planning and provision of palliative care. Despite this, in Chile, palliative care coverage was extended by law to cover nononcological chronic diseases. Implementation of this law is expected to be a significant challenge in terms of material resources, as well as the need for the formation of specialized palliative care teams. Therefore, it is essential to estimate the need for palliative care for all chronic diseases to generate useful input for planning and decision-making in public health.

OBJECTIVES: To indirectly estimate the need for palliative care among people with Chronic Oncological Diseases (COD) and Chronic Non-Oncological Diseases (CNOD) during the prepandemic and pandemic context due to COVID-19 in the Biobío Region in Chile.

METHODS: Cross-sectional study based on mortality data from chronic oncological and nononcological diseases during the prepandemic (2010-2018) and pandemic (2020-2021) contexts due to COVID-19 in a Region of Chile through indirect estimation using minimal estimate, standardized mortality rates and geographically weighted regression.

RESULTS: It was estimated that 76.25% of deaths from chronic diseases in the Biobío Region would have required palliative care, which represents 77,618 people who should have been included in these health benefits. The pandemic had a significant effect on the average number of deaths from CNOD. People belonging to this group were more likely to die from COVID-19 than from their baseline disease, unlike the deaths of people from COD, where no significant changes were observed.

CONCLUSION: These estimates highlight the potential size of the population requiring palliative care and emphasize the importance of recognizing the rights of individuals with COD and CNOD conditions. It is evident that there is a significant demand for palliative care services, as well as a pressing need for adequate resources, effective management, and strategic planning to cater to the needs of this population. This is particularly crucial in the heavily impacted areas and communes of the Biobío Region, Chile.

PMID:37418462 | DOI:10.1371/journal.pone.0288020

Eye Contact Lens. 2023 Jul 3. doi: 10.1097/ICL.0000000000001013. Online ahead of print.

ABSTRACT

PURPOSE: To analyze critically the clinical trials on presbyopia correction with contact lenses (CLs) to investigate the quality of the research performed.

METHODS: A search was performed in PubMed database on clinical trials evaluating the efficacy of the presbyopia correction with different CLs, including multifocal or simultaneous vision contact lenses (MCLs). After a comprehensive analysis of the relevant publications found, quality assessment of such publications was performed by means of Critical Appraisal Skills Programme checklist tool according to the five types of evaluations: MCL versus spectacles, MCL versus pinhole CLs, MCL versus monovision, comparison between MCL designs, and MCL versus extended depth of focus CLs.

RESULTS: A total of 16 clinical trials were selected for evaluation. All evaluated studies addressed a clearly focused research question and were randomized, with a crossover design in most of the cases. Blinding was not possible in all cases due to the physical appearance of some of the CLs evaluated (pinhole or hybrid designs). Most of studies analyzed reported outcomes with complete data, providing the statistical tests used and the P-values, but some of the authors did not provide the statistical power associated to the sample size evaluated. The small sample size in some trials as well as the scarce information about the effect of addition on visual performance was the main limitations found in the peer-reviewed literature revised.

CONCLUSIONS: There is a high-quality scientific evidence supporting the use of presbyopia-correcting CLs, with several randomized controlled clinical trials conducted to this date.

PMID:37418305 | DOI:10.1097/ICL.0000000000001013

Eye Contact Lens. 2023 Jul 4. doi: 10.1097/ICL.0000000000001011. Online ahead of print.

ABSTRACT

OBJECTIVES: In this study, we aimed to evaluate Schlemm canal parameters using anterior segment swept-source optical coherence tomography in eyes that underwent keratoplasty and compare them with keratoconus and healthy control groups.

METHODS: The study included 32 patients who underwent penetrating keratoplasty or deep anterior lamellar keratoplasty once due to keratoconus and age-matched and sex-matched 20 keratoconus patients and 30 healthy controls. In all the patients, a single horizontal image centered on the central cornea was obtained from the nasal and temporal quadrants with low-intensity scanning to visualize Schlemm canal.

RESULTS: There was no statistically significant difference between the groups for age and gender (P˃0.05). In the keratoplasty group, the area and diameter of Schlemm canal were 2.266±1.141μm2 and 160.77±65.08 μm, respectively, in the nasal quadrant and 2.623±1.277 μm2 and 158.81±68.05 μm, respectively in the temporal quadrant, which were statistically significantly lower compared with other groups (P<0.001 for all). There was no significant difference between the penetrating and deep anterior lamellar keratoplasty subgroups for Schlemm canal parameters.

CONCLUSION: This is the first study to report anterior segment optical coherence tomography after surgery shows SC parameters that are, on average, less than age-matched and keratoconus controls.

PMID:37418302 | DOI:10.1097/ICL.0000000000001011