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Nevin Manimala Statistics

Determining seropositivity-A review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases

PLoS Negl Trop Dis. 2021 Jun 28;15(6):e0009457. doi: 10.1371/journal.pntd.0009457. Online ahead of print.

ABSTRACT

BACKGROUND: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays.

METHODOLOGY/PRINCIPAL FINDINGS: A search was conducted in PubMed that that included articles published from January 2010 to January 2020, and 291 relevant articles were identified that included the terms “serology”, “cut-offs”, and “multiplex bead assays”. After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points.

CONCLUSIONS/SIGNIFICANCE: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time.

PMID:34181665 | DOI:10.1371/journal.pntd.0009457

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Nevin Manimala Statistics

De novo mutational signature discovery in tumor genomes using SparseSignatures

PLoS Comput Biol. 2021 Jun 28;17(6):e1009119. doi: 10.1371/journal.pcbi.1009119. Online ahead of print.

ABSTRACT

Cancer is the result of mutagenic processes that can be inferred from tumor genomes by analyzing rate spectra of point mutations, or “mutational signatures”. Here we present SparseSignatures, a novel framework to extract signatures from somatic point mutation data. Our approach incorporates a user-specified background signature, employs regularization to reduce noise in non-background signatures, uses cross-validation to identify the number of signatures, and is scalable to large datasets. We show that SparseSignatures outperforms current state-of-the-art methods on simulated data using a variety of standard metrics. We then apply SparseSignatures to whole genome sequences of pancreatic and breast tumors, discovering well-differentiated signatures that are linked to known mutagenic mechanisms and are strongly associated with patient clinical features.

PMID:34181655 | DOI:10.1371/journal.pcbi.1009119

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Nevin Manimala Statistics

Distancing Measures in COVID-19 Pandemic: Loneliness, More than Physical Isolation, Affects Health Status and Psycho-Cognitive Wellbeing in Elderly Patients with Chronic Obstructive Pulmonary Disease

COPD. 2021 Jun 28:1-6. doi: 10.1080/15412555.2021.1941834. Online ahead of print.

ABSTRACT

Since the outbreak of the SARS-CoV-2 pandemic in 2020, many governments have been imposing confinement and physical distancing measures. No data exist on the effects of lockdowns on the health status of patients affected by chronic pathologies, specifically those with Chronic Obstructive Pulmonary Disease (COPD). Our study aims to establish variations across the psychological and cognitive profile of patients during the isolation period in Italy, in a cohort of patients affected by COPD, between February and May 2020. Forty patients with established COPD were comprehensively evaluated by geriatric multidimensional assessment before the spread of the epidemic in Italy, and submitted to a second evaluation during the subsequent lockdown. We assessed functional ability, basic and instrumental Activities of Daily Living (ADL and IADL), cognition and mood status. We compared the scores obtained at baseline against those obtained during the pandemic, and used mean differences for correlation with major clinical and functional indexes. The score differences from MMSE, ADL and IADL were statistically significant. Such differences were correlated to the presence of a caregiver and to the total number of family members living together. Remarkably, the loneliness dimension, more than the restrictions themselves, seemed to represent the major determinant of altered health status and depressed psycho-cognitive profile in our population. Also remarkably, we detected no correlation between the score variation and the respiratory function indexes of disease severity. The isolation measures adopted during the SARS-CoV-2 pandemic have triggered the classic clinical string associated to geriatric isolation, which leads to a deterioration of cognitive functions, independence and frailty levels in a population affected by a chronic degenerative disease, such as COPD. If considered from a multidimensional geriatric point of view, the individual benefit of isolation measures could be small or non-existent.

PMID:34180766 | DOI:10.1080/15412555.2021.1941834

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Nevin Manimala Statistics

Sequencing of symptom emergence in anorexia nervosa, bulimia nervosa, binge eating disorder, and purging disorder and relations of prodromal symptoms to future onset of these disorders

J Abnorm Psychol. 2021 May;130(4):377-387. doi: 10.1037/abn0000666.

ABSTRACT

The objective of this study was to characterize the temporal sequencing of symptom emergence for anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD), as well as to test whether prodromal symptoms increase risk for future onset of each type of eating disorder and compare the predictive effects to those of established risk factors. Data from four prevention trials that targeted high-risk young women with body image concerns (N = 1,952; Mage = 19.7, SD = 5.7) and collected annual diagnostic interview data over 3-year follow-up were combined to address these aims. Regarding behavioral symptoms, compensatory weight control behaviors typically emerged first for AN, BN, and PD, whereas binge eating typically emerged first for BED. Regarding cognitive symptoms, for AN, weight/shape overvaluation typically emerged first, whereas for BN, BED, and PD, overvaluation typically emerged simultaneously with feeling fat and fear of weight gain. Binge eating, compensatory behaviors, weight/shape overvaluation, fear of weight gain, and feeling fat predicted BN, BED, and PD onset, whereas weight/shape overvaluation, fear of weight gain, and lower than expected body mass index predicted AN onset. Predictive effects of prodromal symptoms were similar in magnitude to those of established risk factors: Collectively, prodromal symptoms and risk factors predicted onset of specific eating disorders with 67-83% accuracy. Results suggest that compensatory weight control behaviors and cognitive symptoms are likely to emerge before binge eating in the various eating disorders and that offering indicated prevention programs to youth with prodromal symptoms may be an effective way to prevent eating disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PMID:34180702 | DOI:10.1037/abn0000666

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Nevin Manimala Statistics

The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial

Cell Transplant. 2021 Jan-Dec;30:9636897211024942. doi: 10.1177/09636897211024942.

ABSTRACT

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

PMID:34180719 | DOI:10.1177/09636897211024942

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Nevin Manimala Statistics

Examining the effectiveness of Trauma Smart® training: Staff satisfaction, knowledge, and attitudes

Psychol Trauma. 2021 Jun 28. doi: 10.1037/tra0001075. Online ahead of print.

ABSTRACT

Objective: Adverse childhood experiences are linked with poorer physical, social, and psychological well-being, especially for individuals who live in poverty. As adverse childhood experiences accumulate, risk for poor outcomes increases. Therefore, it is imperative that preschools and elementary schools are equipped to prevent and intervene upon traumatic stress. Trauma Smart is an organizational change intervention designed to build trauma-informed knowledge, attitudes, skills, and resources within schools serving young children. Method: The current study evaluates the effectiveness of Trauma Smart staff training in 42 preschools and elementary schools with 2,418 staff using a 1-year, longitudinal, prepost design. Trauma Smart implementation occurred during scale-up, under real world conditions. Satisfaction, posttraining knowledge about trauma-informed approaches, and pre-to-posttraining changes in attitudes favorable to trauma-informed care were evaluated. Results: As hypothesized, staff were highly satisfied with the training (mean ratings indicate 92% satisfied), demonstrated knowledge of core concepts related to trauma-informed care (mean quiz scores were scored 90% correct), and developed more favorable attitudes toward trauma-informed care following training, with medium-large effect sizes. Conclusions: Trauma Smart staff training is feasible, acceptable, and has the potential to improve the knowledge and attitudes relevant to trauma-informed approaches within preschool and elementary school staff, including those who serve children who live in poverty. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PMID:34180686 | DOI:10.1037/tra0001075

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Psychometric properties of the Depressive Symptom Index-Suicidality Subscale (DSI-SS) in an adult psychiatric sample

Psychol Assess. 2021 Jun 28. doi: 10.1037/pas0001043. Online ahead of print.

ABSTRACT

The Depressive Symptom Index-Suicidality Subscale (DSI-SS) is a four-item self-report measure of suicidal ideation severity widely used across research and clinical contexts. However, the psychometric properties of the English-language version of the DSI-SS have not been extensively examined within a psychiatric sample, and important properties of this scale (e.g., sensitivity to change) have yet to be examined. Within a sample of 448 adult psychiatric patients enrolled in a partial hospital program (PHP), we examined several measurement properties of the DSI-SS, including its factor structure, internal consistency, validity, and sensitivity to change, as well as the presence of differential item functioning (DIF). Confirmatory factor analysis that specified a one-factor model indicated that the DSI-SS had good model fit. DSI-SS scores demonstrated good internal consistency, ω = .90 [95% CI = .89-.91], convergent validity (rs = .52-.74), discriminant validity (rs = .12-.27), and sensitivity to change. None of the four DSI-SS items evinced statistically significant DIF across age, gender, sexual orientation, or PHP referral source (i.e., outpatient step-up vs. inpatient step-down). These findings suggest that the DSI-SS is a psychometrically sound self-report measure that can be used in real-world clinical settings and research contexts to reliably and validly assess suicidal ideation severity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PMID:34180693 | DOI:10.1037/pas0001043

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Nevin Manimala Statistics

Subtypes of the missing not at random missing data mechanism

Psychol Methods. 2021 Jun 28. doi: 10.1037/met0000377. Online ahead of print.

ABSTRACT

issing values that are missing not at random (MNAR) can result from a variety of missingness processes. However, two fundamental subtypes of MNAR values can be obtained from the definition of the MNAR mechanism itself. The distinction between them deserves consideration because they have characteristic differences in how they distort relationships in the data. This has implications for the validity of statistical results and generalizability of methodological findings that are based on data (empirical or generated) with MNAR values. However, these MNAR subtypes have largely gone unnoticed by the literature. As few studies have considered both subtypes, their relevance to methodological and substantive research has been overlooked. This article systematically introduces the two MNAR subtypes and gives them descriptive names. A case study demonstrates they are mechanically distinct from each other and from other missing-data mechanisms. Applied examples are given to help researchers conceptually identify MNAR subtypes in real data. Methods are provided to generate missing values from both subtypes in simulation studies. Simulation studies for regression and growth curve modeling contexts show MNAR subtypes consistently differ in the severity of their impact on statistical inference. This behavior is examined in light of how relationships in the data become characteristically distorted. The contents of this article are intended to provide a foundation and tools for organized consideration of MNAR subtypes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PMID:34180695 | DOI:10.1037/met0000377

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Clinical and surgical approaches for malignant pulmonary lesions after a previous extrapulmonary malignancy

ANZ J Surg. 2021 Jun 28. doi: 10.1111/ans.17045. Online ahead of print.

ABSTRACT

BACKGROUND: In our study, since the operative histopathological distinction of new malignant pulmonary lesions as either a primary lung cancer or a pulmonary metastasis is difficult, we aimed to identify the clinical variables which might allow distinction between a new lung cancer and a pulmonary metastasis, and the appropriate surgical management.

METHODS: We divided 55 cases into two groups: patients with new lung cancer (NLC, n = 32) and patients with pulmonary metastases (PM, n = 23). Based on the primary organ, the previous malignancy was classified into four categories: head and neck, colorectal, genitourinary, and breast cancer. The parameters included in the study were age, sex, smoking history, a family history of cancer, disease-free interval, primary organ, treatments for previous malignancies, size, and SUV max of the lung lesion on 18F-fluorodeoxyglucose positron emission tomography scan and high-resolution computed tomography findings of the lung lesion.

RESULTS: A predisposition for larger lesions was found in the NLC group. In addition, in the NLC group, disease-free interval was noted to be longer, patients were significantly older and SUV-max values of solitary pulmonary lesions were significantly higher than in the PM group. Pulmonary lesions in patients with prior head and neck cancers were more likely to develop NLC. No significant difference in statistical analysis was observed between the groups in terms of sex, smoking, a family history of cancer, a history of adjuvant therapy, radiological pulmonary lesions signs, and localization.

CONCLUSION: PL monitoring on CT surveillance is essential, particularly in patients with previous head and neck cancers, who appear to have a higher risk for NLC. If pathological MLN accompanies PL in a patient with previous extrapulmonary malignancy, cervical mediastinoscopy may help acquire a possible PL diagnosis besides mediastinal staging. Intraoperative frozen section may have difficulty in distinguishing between PM and NLC when the lesion is of the same histological type as the previous malignancy. When precise distinction cannot be achieved by frozen section, we speculate that DFI, age, and radiological findings of the PL may help thoracic surgeons take initiative peroperatively while designating the subsequent surgical intervention. Lastly, pulmonary segmentectomy is also better be considered along with lobectomy in NLC cases.

PMID:34180584 | DOI:10.1111/ans.17045

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Nevin Manimala Statistics

Metabolic profiling analysis of the vitamin B12 producer Propionibacterium freudenreichii

Microbiologyopen. 2021 Jun;10(3):e1199. doi: 10.1002/mbo3.1199.

ABSTRACT

Vitamin B12 (VB12 ) is an indispensable cofactor of metabolic enzymes and has been widely used in the food and pharmaceutical industries. In this study, the effects of medium composition on VB12 production by Propionibacterium freudenreichii were evaluated and optimized based on statistical experiments. The results showed that glucose, yeast extract, KH2 PO4 , and glycine have significant effects on VB12 production. The final titer of VB12 reached 8.32 ± 0.02 mg/L, representing a 120% increase over the non-optimized culture medium. We employed a metabolomics approach to analyze the differences of metabolite concentrations in P. freudenreichii cells cultivated in the original medium and optimized fermentation medium. Using multivariate data analysis, we identified a range of correlated metabolites, illustrating how metabolomics can be used to explain VB12 production changes by corresponding differences in the overall cellular metabolism. The concentrations of many metabolic intermediates of glycolysis, the Wood-Werkman cycle, the TCA cycle, and amino acid metabolism were increased, which contributed to the synthesis of propionic acid and VB12 due to an improved supply of energy and precursors.

PMID:34180597 | DOI:10.1002/mbo3.1199