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Nevin Manimala Statistics

Bayesian networks elucidate complex genomic landscapes in cancer

Commun Biol. 2022 Apr 4;5(1):306. doi: 10.1038/s42003-022-03243-w.

ABSTRACT

Bayesian networks (BNs) are disciplined, explainable Artificial Intelligence models that can describe structured joint probability spaces. In the context of understanding complex relations between a number of variables in biological settings, they can be constructed from observed data and can provide a guiding, graphical tool in exploring such relations. Here we propose BNs for elucidating the relations between driver events in large cancer genomic datasets. We present a methodology that is specifically tailored to biologists and clinicians as they are the main producers of such datasets. We achieve this by using an optimal BN learning algorithm based on well established likelihood functions and by utilising just two tuning parameters, both of which are easy to set and have intuitive readings. To enhance value to clinicians, we introduce (a) the use of heatmaps for families in each network, and (b) visualising pairwise co-occurrence statistics on the network. For binary data, an optional step of fitting logic gates can be employed. We show how our methodology enhances pairwise testing and how biologists and clinicians can use BNs for discussing the main relations among driver events in large genomic cohorts. We demonstrate the utility of our methodology by applying it to 5 cancer datasets revealing complex genomic landscapes. Our networks identify central patterns in all datasets including a central 4-way mutual exclusivity between HDR, t(4,14), t(11,14) and t(14,16) in myeloma, and a 3-way mutual exclusivity of three major players: CALR, JAK2 and MPL, in myeloproliferative neoplasms. These analyses demonstrate that our methodology can play a central role in the study of large genomic cancer datasets.

PMID:35379892 | DOI:10.1038/s42003-022-03243-w

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Nevin Manimala Statistics

Unimpaired groupitizing in children and adolescents with dyscalculia

Sci Rep. 2022 Apr 4;12(1):5629. doi: 10.1038/s41598-022-09709-5.

ABSTRACT

When asked to estimate the number of items in the visual field, neurotypical adults are more precise and rapid if the items are clustered into subgroups compared to when they are randomly distributed. It has been suggested that this phenomenon, termed “groupitizing”, relies on the recruitment of arithmetical calculation strategies and subitizing. Here the role of arithmetical skills in groupitizing was investigated by measuring the groupitizing effect (or advantage) in a sample of children and adolescents with and without math learning disability (dyscalculia). The results showed that when items were grouped, both groups of participants showed a similar advantage on sensory precision and response time in numerosity estimates. Correlational analyses confirmed a lack of covariation between groupitizing advantage and math scores. Bayesian statistics on sensory precision sustained the frequentist analyses providing decisive evidence in favor of no groups difference on groupitizing advantage magnitude (LBF = – 0.44) and no correlation with math scores (LBF = – 0.57). The results on response times, although less decisive, were again in favor of the null hypothesis. Overall, the results suggest that the link between groupitizing and mathematical abilities cannot be taken for granted, calling for further investigations on the factors underlying this perceptual phenomenon.

PMID:35379895 | DOI:10.1038/s41598-022-09709-5

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Nevin Manimala Statistics

Chromatic discrimination in fixed saturation levels from trichromats and subjects with congenital color vision deficiency

Sci Rep. 2022 Apr 4;12(1):5603. doi: 10.1038/s41598-022-09531-z.

ABSTRACT

Color vision tests use estimative of threshold color discrimination or number of correct responses to evaluate performance in chromatic discrimination tasks. Both approaches have advantages and disadvantages. In the present investigation, we compared the number of errors during color discrimination task in normal trichromats and participants with color vision deficiency (CVD) using pseudoisochromatic stimuli at fixed saturation levels. We recruited 28 normal trichromats and eight participants with CVD. Cambridge Color Test was used to categorize their color vision phenotype, and those with a phenotype suggestive of color vision deficiency had their L- and M-opsin genes genotyped. Pseudoisochromatic stimuli were shown with target chromaticity in 20 vectors radiating from the background chromaticity and saturation of 0.06, 0.04, 0.03, 0.02, 0.01, and 0.005 u’v’ units. Each stimulus condition appeared in four trials. The number of errors for each stimulus condition was considered an indicator of the participant’s performance. At high chromatic saturation, there were fewer errors from both phenotypes. The errors of the normal trichromats had no systematic variation for high saturated stimuli, but below 0.02 u’v’ units, there was a discrete prevalence of tritan errors. For participants with CVD, the errors happened mainly in red-green chromatic vectors. A three-way ANOVA showed that all factors (color vision phenotype, stimulus saturation, and chromatic vector) had statistically significant effects on the number of errors and that stimulus saturation was the most important main effect. ROC analysis indicated that the performance of the fixed saturation levels to identify CVD was better between 0.02 and 0.06 u’v’ units reaching 100%, while saturation of 0.01 and 0.005 u’v’ units decreased the accuracy of the screening of the test. We concluded that the color discrimination task using high saturated stimuli separated normal trichromats and participants with red-green color vision deficiencies with high performance, which can be considered a promising method for new color vision tests based in frequency of errors.

PMID:35379850 | DOI:10.1038/s41598-022-09531-z

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Nevin Manimala Statistics

Addressing the range anxiety of battery electric vehicles with charging en route

Sci Rep. 2022 Apr 4;12(1):5588. doi: 10.1038/s41598-022-08942-2.

ABSTRACT

Battery electric vehicles (BEVs) have emerged as a promising alternative to traditional internal combustion engine (ICE) vehicles due to benefits in improved fuel economy, lower operating cost, and reduced emission. BEVs use electric motors rather than fossil fuels for propulsion and typically store electric energy in lithium-ion cells. With rising concerns over fossil fuel depletion and the impact of ICE vehicles on the climate, electric mobility is widely considered as the future of sustainable transportation. BEVs promise to drastically reduce greenhouse gas emissions as a result of the transportation sector. However, mass adoption of BEVs faces major barriers due to consumer worries over several important battery-related issues, such as limited range, long charging time, lack of charging stations, and high initial cost. Existing solutions to overcome these barriers, such as building more charging stations, increasing battery capacity, and stationary vehicle-to-vehicle (V2V) charging, often suffer from prohibitive investment costs, incompatibility to existing BEVs, or long travel delays. In this paper, we propose Peer-to-Peer Car Charging (P2C2), a scalable approach for charging BEVs that alleviates the need for elaborate charging infrastructure. The central idea is to enable BEVs to share charge among each other while in motion through coordination with a cloud-based control system. To re-vitalize a BEV fleet, which is continuously in motion, we introduce Mobile Charging Stations (MoCS), which are high-battery-capacity vehicles used to replenish the overall charge in a vehicle network. Unlike existing V2V charging solutions, the charge sharing in P2C2 takes place while the BEVs are in-motion, which aims at minimizing travel time loss. To reduce BEV-to-BEV contact time without increasing manufacturing costs, we propose to use multiple batteries of varying sizes and charge transfer rates. The faster but smaller batteries are used for charge transfer between vehicles, while the slower but larger ones are used for prolonged charge storage. We have designed the overall P2C2 framework and formalized the decision-making process of the cloud-based control system. We have evaluated the effectiveness of P2C2 using a well-characterized simulation platform and observed dramatic improvement in BEV mobility. Additionally, through statistical analysis, we show that a significant reduction in carbon emission is also possible if MoCS can be powered by renewable energy sources.

PMID:35379831 | DOI:10.1038/s41598-022-08942-2

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Nevin Manimala Statistics

Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells

Nat Commun. 2022 Apr 4;13(1):1789. doi: 10.1038/s41467-022-29426-x.

ABSTRACT

The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis. Furthermore, Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally, Gclc deficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. Our results thus suggest that Gclc is required to ensure the development of MZB, the mitochondrial ETC integrity in FoB, and the efficacy of antiviral humoral immunity.

PMID:35379825 | DOI:10.1038/s41467-022-29426-x

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Nevin Manimala Statistics

Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation

Ann Transplant. 2022 Apr 5;27:e935604. doi: 10.12659/AOT.935604.

ABSTRACT

BACKGROUND Liver transplantation (LT) has been validated widely all over the world as the curative treatment for hepatocellular carcinoma (HCC). Statins have been reported to prevent the progression of HCC. There are many factors that affect recurrence of HCC, but the precise role of statins is unknown. Therefore, we examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent living-donor LT (LDLT) for HCC. MATERIAL AND METHODS We retrospectively analyzed 844 HCC patients who underwent primary adult-to-adult LDLT in our center between January 2007 and December 2016. Statin therapy was defined as administration of statins for more than 30 cumulative defined daily doses (cDDDs) after LT. We compared HCC recurrence and patient survival between non-statin (n=334) and statin (n=52) groups. RESULTS The recurrence rate was higher in the non-statin group; however, time-dependent multivariate analysis with Kaplan-Meier curves showed that statin users did not significantly benefit in terms of HCC recurrence-related survival or overall survival. Further, risk factor analysis of HCC recurrence and patient survival confirmed multiple regional treatments (≥3 times), high alpha fetoprotein level (≥100 ng/mL), large tumor size (≥3 cm), and microvascular invasion as risk factors for HCC recurrence, but statin treatment was not associated with a significantly lower recurrence rate of HCC or reduced mortality after adjusting for other risk factors. CONCLUSIONS Statin use might be associated with prevention of HCC progression, but no significant decrease in HCC recurrence rates in LDLT patients was recorded in this study.

PMID:35379768 | DOI:10.12659/AOT.935604

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Nevin Manimala Statistics

sTREM2 mediates the associations of minimal depressive symptoms with amyloid pathology in prodromal Alzheimer’s disease: The CABLE study

Transl Psychiatry. 2022 Apr 4;12(1):140. doi: 10.1038/s41398-022-01910-4.

ABSTRACT

The effects of microglial activation on the associations between depression and Alzheimer’s disease (AD) are still unclear. TREM2 gene plays a pivotal role in microglial activation, has been identified as a risk factor for AD. In this work, we aimed to assess the interrelationships of soluble TREM2 (sTREM2) level in cerebrospinal fluid (CSF), minimal depressive symptoms (MDSs), and CSF amyloid markers. The linear regression analyses were conducted on 796 cognitively unimpaired participants from the CABLE (Chinese Alzheimer’s Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were used to test the mediation effects. In addition, similar statistical analyses were performed in subgroups stratified by sex, age, and APOE ε4 carrier status. In total subjects, MDSs were associated with lower CSF sTREM2 levels (p < 0.0001), lower CSF amyloid markers (p < 0.0001), and poorer cognitive performance (MMSE, p = 0.0014). The influence of MDSs on CSF amyloid markers was partially mediated by CSF sTREM2 (proportion from 2.91 to 32.58%, p < 0.0001). And we found that the sTREM2-amyloid pathway partially mediated the effects of MDSs on cognition. Of note, exploratory subgroup analyses showed that the above influences of CSF sTREM2 were pronounced in the APOE ε4 (-) group. These results suggest that early depression is associated with amyloid pathology, which might be partly mediated by microglial activation, especially in the absence of APOE ε4.

PMID:35379792 | DOI:10.1038/s41398-022-01910-4

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Nevin Manimala Statistics

Oncology and Primary Care Provider Views on Cancer Survivorship Care: Mind the Gap

J Am Board Fam Med. 2022 Mar-Apr;35(2):329-340. doi: 10.3122/jabfm.2022.02.210286.

ABSTRACT

CONTEXT: Coordination between oncology and primary care practices in cancer survivorship is lacking.

OBJECTIVE: To identify cancer care coordination perceptions, knowledge, and practices in a sample of Oklahoma oncology care providers (ONCs) and primary care providers (PCPs) regarding post-treatment care of adult cancer survivors.

DESIGN: Cross-sectional, statewide survey by mail/web link in 2014/5.

SETTING: PCPs identified through a primary care research network, primary care organization membership lists; ONCs identified through www.Healthgrades.com.

PARTICIPANTS: Contacts who were clinically active and seeing cancer patients were eligible. The final sample size included 101 ONCs and 58 PCPs who reported actively seeing cancer patients.

MEASURES: Responses to predominately Likert scale or ranked-order questions derived from the Survey of Physician Attitudes Regarding the Care of Cancer Survivors.

ANALYSES: Chi square and t tests were performed to test bivariate associations between provider type and survey measures.

RESULTS: Statistically significant differences (P < .05) between ONC and PCP perceptions were observed for several questions on communication between the 2 provider types, ONC perceptions of PCP ability to address survivorship care, and responsibilities for post-treatment care.

CONCLUSIONS: Highly discrepant perspectives between ONCs and PCPs regarding communications and responsibilities for survivorship care may lead to adverse health outcomes. Interventions aimed at improving care coordination for cancer survivors should define each provider group’s responsibilities in survivorship care, and create structures and processes that foster clear channels of communication between ONC and PCP practices.

PMID:35379720 | DOI:10.3122/jabfm.2022.02.210286

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Nevin Manimala Statistics

Assessing the Adequacy of Obstructive Sleep Apnea Diagnosis for High-Risk Patients in Primary Care

J Am Board Fam Med. 2022 Mar-Apr;35(2):320-328. doi: 10.3122/jabfm.2022.02.210296.

ABSTRACT

INTRODUCTION: The exact prevalence of obstructive sleep apnea (OSA) is unknown, and primary care providers are left with conflicting guidance on screening criteria from various institutions. The purpose of this study was to identify health care gaps in OSA diagnosis for patients at high risk of OSA.

METHODS: A retrospective medical record review was performed assessing adult patients (≥ 18 years) who had outpatient visits in family medicine clinics, located in the cities of Detroit, Troy, and Commerce, Michigan in 2018. The primary outcome was the number of patients assessed for OSA. Patients determined as high risk for OSA had at least 3 of the following criteria: (1) hypertension, (2) age 50 years and older, (3) male gender, and (4) body mass index > 35 kg/m2. Statistical approach included univariate and logistic regression analysis. Manual chart review of 200 randomly selected records was performed to determine the most common reasons for OSA screening.

RESULTS: Out of 30,022 patients, 4,911 (16.4%) were at high risk for OSA, of which 1,524 (31.0%) were assessed for OSA. Logistic regression analysis of high-risk patients revealed that male sex (odds ratio, 1.84; 95% CI, 1.51-2.26; P < .001) and body mass index > 35 kg/m2 (odds ratio, 4.96; 95% CI, 4.04-6.09; P < .001) were significantly associated with OSA evaluation. Race was not associated with OSA assessment.

CONCLUSION: Because many individuals at high risk for OSA are not referred for evaluation, improved guidance on OSA screening based on objective risk factors is needed.

PMID:35379719 | DOI:10.3122/jabfm.2022.02.210296

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Nevin Manimala Statistics

Validating the Group-Based Medical Mistrust Scale with English and Spanish Speaking Latino Parents of Adolescents

J Am Board Fam Med. 2022 Mar-Apr;35(2):244-254. doi: 10.3122/jabfm.2022.02.210307.

ABSTRACT

BACKGROUND: Medical mistrust can be a barrier to health care utilization. While the Group-Based Medical Mistrust Scale (GBMMS) has been validated among diverse populations, we know little about its psychometric performance among English-Speaking (ES) and Spanish-Speaking (SS) Latinos. We aim to examine the factor structure of GBMMS among Latino parents and explore whether scale latent factor structures would be different across preferred languages.

METHODS: Parents of adolescents participating in an urban academic enrichment program for low-income students completed an online survey as part of a cross-sectional study about Human Papillomavirus (HPV) prevention. We tested the validity of the GBMMS in ES and SS respondents and performed exploratory factor analysis to identify latent factors. We examined scale scores, item means, item endorsement, and residual variance across language groups.

RESULTS: 2-factor latent structure was identified for both ES and SS groups; factors were labeled as ‘Suspicion’ and ‘System-wide discrimination.’ Scale validity was better among SS (α = 0.76). Medical mistrust scores did not vary across language groups, but variation emerged in item endorsement by language.

DISCUSSION: Our results suggest that the factor structures of the medical mistrust construct, measured by the GBMMS, are similar across ES and SS Latinos and that the GBMMS is valid for both populations. High factor pattern loading reflects a shared mistrust of how health care systems view and treat people of their racial/ethnic background, independent of their preferred languages. Measurement of medical mistrust and identifying its underlying causes are needed within diverse populations to fully address structural- and community-level influences on health inequities.

PMID:35379712 | DOI:10.3122/jabfm.2022.02.210307