Category: Nevin Manimala

Paediatr Perinat Epidemiol. 2022 Jan 25. doi: 10.1111/ppe.12863. Online ahead of print.

ABSTRACT

BACKGROUND: Large-scale evaluation of COVID-19 is likely to rely on the quality of ICD coding. However, little is known about the validity of ICD-coded COVID-19 diagnoses.

OBJECTIVES: To evaluate the performance of diagnostic codes in detecting COVID-19 during pregnancy.

METHODS: We used data from a national cohort of 78,283 individuals with a pregnancy ending between 11 March 2020 and 31 January 2021 in the OptumLabs^® Data Warehouse (OLDW). OLDW is a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data. We identified all services with an ICD-10-CM diagnostic code of U07.1 and all laboratory claims records for COVID-19 diagnostic testing. We compared ICD-coded diagnoses to testing results to estimate positive and negative predictive values (PPV and NPV). To evaluate impact on risk estimation, we estimated risk of adverse pregnancy outcomes by source of exposure information.

RESULTS: Of 78,283 pregnancies, 5644 had a laboratory test result for COVID-19. Testing was most common among older individuals, Hispanic individuals, those with higher socioeconomic status and those with a diagnosed medical condition or pregnancy complication; 52% of COVID-19 cases was identified through ICD-coded diagnosis alone, 19% from laboratory test results alone and 29% from both sources. Agreement between ICD-coded diagnosis and laboratory testing records was high 91% (95% confidence interval [CI] 90, 92). However, the PPV of ICD-code diagnosis was low (36%; 95% CI 33, 39). We observed up to a 50% difference in risk estimates of adverse pregnancy outcomes when exposure was based on laboratory testing results or diagnostic coding alone.

CONCLUSIONS: More than one-in-five COVID-19 cases would be missed by using ICD-coded diagnoses alone to identify COVID-19 during pregnancy. Epidemiological studies exclusively relying on diagnostic coding or laboratory testing results are likely to be affected by exposure misclassification. Research and surveillance should draw upon multiple sources of COVID-19 diagnostic information.

PMID:35077581 | DOI:10.1111/ppe.12863

Hum Mol Genet. 2021 Nov 19:ddab339. doi: 10.1093/hmg/ddab339. Online ahead of print.

ABSTRACT

Mitochondria have a complex communication network with the surrounding cell and can alter nuclear DNA methylation (DNAm). Variation in the mitochondrial DNA (mtDNA) has also been linked to differential DNAm. Genome-wide association studies have identified numerous DNAm quantitative trait loci, but these studies have not examined the mitochondrial genome. Herein, we quantified nuclear DNAm from blood and conducted a mitochondrial genome-wide association study of DNAm, with an additional emphasis on sex- and prediabetes-specific heterogeneity. We used the Young Finns Study (n = 926) with sequenced mtDNA genotypes as a discovery sample and sought replication in the Ludwigshafen Risk and Cardiovascular Health study (n = 2317). We identified numerous significant associations in the discovery phase (P < 10-9), but they were not replicated when accounting for multiple testing. In total, 27 associations were nominally replicated with a P < 0.05. The replication analysis presented no evidence of sex- or prediabetes-specific heterogeneity. The 27 associations were included in a joint meta-analysis of the two cohorts, and 19 DNAm sites associated with mtDNA variants, while four other sites showed haplogroup associations. An expression quantitative trait methylation analysis was performed for the identified DNAm sites, pinpointing two statistically significant associations. This study provides evidence of a mitochondrial genetic control of nuclear DNAm with little evidence found for sex- and prediabetes-specific effects. The lack of a comparable mtDNA data set for replication is a limitation in our study and further studies are needed to validate our results.

PMID:35077545 | DOI:10.1093/hmg/ddab339

Cancer. 2022 Jan 25. doi: 10.1002/cncr.34103. Online ahead of print.

ABSTRACT

BACKGROUND: The management of myelofibrosis (MF) has changed over the last several years and could have an impact on patient outcome. This study evaluates the survival of patients with MF at the authors’ institution to determine whether it changed in the last decade.

METHODS: This retrospective study consists of 844 patients (64% male; median age, 66 years; range, 20-90 years) who were examined between 2000 and 2020 with a new diagnosis of MF. Only patients with available marrow biopsy who had reticulin fibrosis of grade 2 or higher were included. Patients were compared by year of presentation: 2000-2010 (n = 373) and 2011-2020 (n = 471).

RESULTS: A statistically significant improvement in median survival in the last decade was noted: from 48 months (95% CI, 42-54 months) to 63 months (95% CI, 55-71 months) (P < .001; HR, 0.78 [95% CI, 0.64-0.95]). Improved survival was observed also in patients 65 years old or older and those having intermediate 2 or high-risk Dynamic International Prognostic Scoring System (DIPSS) or DIPSS-Plus risk scores. Among 532 patients treated with MF-directed therapy, patients exposed to JAK inhibitor ruxolitinib had superior outcomes with median overall survival of 84 months (95% CI, 70-94 months).

CONCLUSIONS: The results demonstrate that survival of patients with MF has improved in the last decade. This improvement is likely due to increased disease awareness, advances in supportive care, and the development of effective treatments.

PMID:35077575 | DOI:10.1002/cncr.34103

Gigascience. 2022 Jan 25;11:giab088. doi: 10.1093/gigascience/giab088.

ABSTRACT

BACKGROUND: Mitigating the effects of global warming has become the main challenge for humanity in recent decades. Livestock farming contributes to greenhouse gas emissions, with an important output of methane from enteric fermentation processes, mostly in ruminants. Because ruminal microbiota is directly involved in digestive fermentation processes and methane biosynthesis, understanding the ecological relationships between rumen microorganisms and their active metabolic pathways is essential for reducing emissions. This study analysed whole rumen metagenome using long reads and considering its compositional nature in order to disentangle the role of rumen microbes in methane emissions.

RESULTS: The β-diversity analyses suggested a subtle association between methane production and overall microbiota composition (0.01 < R2 < 0.02). Differential abundance analysis identified 36 genera and 279 KEGGs as significantly associated with methane production (Padj < 0.05). Those genera associated with high methane production were Eukaryota from Alveolata and Fungi clades, while Bacteria were associated with low methane emissions. The genus-level association network showed 2 clusters grouping Eukaryota and Bacteria, respectively. Regarding microbial gene functions, 41 KEGGs were found to be differentially abundant between low- and high-emission animals and were mainly involved in metabolic pathways. No KEGGs included in the methane metabolism pathway (ko00680) were detected as associated with high methane emissions. The KEGG network showed 3 clusters grouping KEGGs associated with high emissions, low emissions, and not differentially abundant in either. A deeper analysis of the differentially abundant KEGGs revealed that genes related with anaerobic respiration through nitrate degradation were more abundant in low-emission animals.

CONCLUSIONS: Methane emissions are largely associated with the relative abundance of ciliates and fungi. The role of nitrate electron acceptors can be particularly important because this respiration mechanism directly competes with methanogenesis. Whole metagenome sequencing is necessary to jointly consider the relative abundance of Bacteria, Archaea, and Eukaryota in the statistical analyses. Nutritional and genetic strategies to reduce CH4 emissions should focus on reducing the relative abundance of Alveolata and Fungi in the rumen. This experiment has generated the largest ONT ruminal metagenomic dataset currently available.

PMID:35077540 | DOI:10.1093/gigascience/giab088

PLoS One. 2022 Jan 25;17(1):e0263094. doi: 10.1371/journal.pone.0263094. eCollection 2022.

ABSTRACT

BACKGROUND: Perforation of the lingual plate in the apical region of mandibular third molars will increase the risk of aberration and migration of the root tip and the risk of lingual nerve injury. The aim of this study was to analyze anatomical information, including relationships between the apical region of horizontally impacted mandibular third molars and lingual plates, in young Japanese.

METHODS: Japanese patients, with horizontally impacted third molars, who underwent CT examination as a preoperative assessment for mandibular third molar extraction were included, and anatomical characteristics in the apical region of the right mandibular third molar were analyzed, in this study.

RESULTS: A total of 121 patients were included based on the inclusion and exclusion criteria of this study. The mean and standard deviation of the bone thickness on the lingual side of the mandibular third molar in the apical region was 1.5 ± 1.6 mm, and the absence of lingual cortical bone in the apical region, namely, “perforation”, was observed in 44 patients. The statistical analysis revealed the predictors of cases with perforation as follows: gender, age, and the available space evaluated by Pell and Gregory classification.

CONCLUSIONS: This study clarified that “perforation” was sometimes observed in young Japanese, and that the predictors of those cases were as follows: gender, age, and the available space evaluated by Pell and Gregory classification.

PMID:35077519 | DOI:10.1371/journal.pone.0263094

Gigascience. 2022 Jan 25;11:giab092. doi: 10.1093/gigascience/giab092.

ABSTRACT

BACKGROUND: The increasing availability of multi-omics data is leading to regularly revised estimates of existing biodiversity data. In particular, the molecular data enable novel species to be characterized and the information linked to those already observed to be increased with new genomics data. For this reason, the management and visualization of existing molecular data, and their related metadata, through the implementation of easy-to-use IT tools have become a key point to design future research. The more users are able to access biodiversity-related information, the greater the ability of the scientific community to expand its knowledge in this area.

RESULTS: In this article we focus on the development of ExTaxsI (Exploring Taxonomy Information), an IT tool that can retrieve biodiversity data stored in NCBI databases and provide a simple and explorable visualization. We use 3 case studies to show how an efficient organization of the available data can lead to obtaining new information that is fundamental as a starting point for new research. Using this approach highlights the limits in the distribution of data availability, a key factor to consider in the experimental design phase of broad-spectrum studies such as metagenomics.

CONCLUSIONS: ExTaxsI can easily retrieve molecular data and its metadata with an explorable visualization, with the aim of helping researchers to improve experimental designs and highlight the main gaps in the coverage of available data.

PMID:35077538 | DOI:10.1093/gigascience/giab092

PLoS One. 2022 Jan 25;17(1):e0263092. doi: 10.1371/journal.pone.0263092. eCollection 2022.

ABSTRACT

Knowledge about the relation of histopathological characteristics and mediators of physiological processes in the placenta malaria (PM) is poor, and that PM caused by Plasmodium vivax is almost null. The objective was to compare histopathological characteristics, cytokines and mediators of physiological processes in PM depending on the parasitic species, through a cross-sectional study in three groups: negative-PM, vivax-PM, falciparum-PM from Northwestern Colombia. The diagnosis of PM was made with thick blood smear, qPCR, and histopathology. Immuno-histochemical was made with EnVision system (Dako) and Zeiss Axio Imager M2 with light microscope. Cells in apoptosis were studied with the TUNEL technique. To measure the expression level of cytokines and mediators qRT-PCR was used. We included 179 placentas without PM and 87 with PM (53% P. vivax and 47% P. falciparum). At delivery, anemia was 25% in negative-PM, 60% in vivax-PM, and 44% in falciparum-PM group. The neonatal weight had an intense difference between groups with 3292±394g in negative-PM, 2,841±239 in vivax-PM, and 2,957±352 in falciparum-PM. The histopathological characteristics and CD+ cells in placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were infarction, fibrinoid deposits, calcification, cells in apoptosis, immune infiltrates in decidua and intervillous space, CD4+, CD8+, CD14+, CD56+, CD68+. The expression levels of mediators in the placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were Fas, FasL, HIF1α, Cox1, Cox2, VEGF, IL4, IL10, IFNγ, TNF, TGFβ, FOXP3, and CTLA4. PM with P. falciparum and P. vivax, damages this organ and causes significant alteration of various physiological processes, which cause maternal anemia and a reduction in neonatal weight in degrees that are statistically and clinically significant. It is necessary that the search for plasmodial infection in pregnant and placenta goes from passive to active surveillance with adequate diagnostic capacity.

PMID:35077516 | DOI:10.1371/journal.pone.0263092

PLoS One. 2022 Jan 25;17(1):e0262944. doi: 10.1371/journal.pone.0262944. eCollection 2022.

ABSTRACT

Latent class analysis is a widely used statistical method for evaluating diagnostic tests without any gold standard. It requires the results of at least two tests applied to the same individuals. Based on the resulting response patterns, the method estimates the test accuracy and the unknown disease status for all individuals in the sample. An important assumption is the conditional independence of the tests. If tests with the same biological principle are used, the assumption is not fulfilled, which may lead to biased results. In a recent publication, we developed a method that considers the dependencies in the latent class model and estimates all parameters using frequentist methods. Here, we evaluate the practicability of the method by applying it to the results of six ELISA tests for antibodies against the porcine reproductive and respiratory syndrome (PRRS) virus in pigs that generally follow the same biological principle. First, we present different methods of identifying suitable starting values for the algorithm and apply these to the dataset and a vaccinated subgroup. We present the calculated values of the test accuracies, the estimated proportion of antibody-positive animals and the dependency structure for both datasets. Different starting values led to matching results for the entire dataset. For the vaccinated subgroup, the results were more dependent on the selected starting values. All six ELISA tests are well suited to detect antibodies against PRRS virus, whereas none of the tests had the best values for sensitivity and specificity simultaneously. The results thus show that the method used is able to determine the parameter values of conditionally dependent tests with suitable starting values. The choice of test should be based on the general fit-for-purpose concept and the population under study.

PMID:35077518 | DOI:10.1371/journal.pone.0262944

PLoS One. 2022 Jan 25;17(1):e0262936. doi: 10.1371/journal.pone.0262936. eCollection 2022.

ABSTRACT

The majority of musculoskeletal modelling studies investigating healthy populations use generic models linearly scaled to roughly match an individual’s anthropometry. Generic models disregard the considerable variation in musculoskeletal geometry and tissue properties between individuals. This study investigated the physiological implications of personalizing musculoskeletal model geometry (body segment mass, inertia, joint center, and maximum isometric muscle force). Nine healthy athletes performed ten repetitions of 15 meter sprints at 75-95% of their maximum sprinting speed and ten repetitions of unanticipated sidestep cut trials with a 4.5-5.5 m/s approach running speed. Structural magnetic resonance imaging was collected on the lower extremities, from which subject-specific musculoskeletal models were developed. A one-dimensional statistical parametric mapping paired t-test was used to compare generic and subject-specific musculoskeletal models for: lower-limb kinematics, kinetics, torque matching, as well as hamstrings, adductors, and quadriceps muscle activations and fiber dynamics. Percentage change of geometric parameters between generic and subject-specific models were determined. Compared to generic models, subject-specific models showed significantly lower ankle dorsi/plantar flexion angle during sprinting and several significantly different net joint moments during sprint and cut tasks. Additionally, subject-specific models demonstrated better torque matching, more physiologically plausible fiber lengths, higher fiber velocities, lower muscle forces, and lower simulated activations in a subset of investigated muscles and motor tasks. Furthermore, subject-specific models identified between-limb differences that were not identified with generic models. Use of subject-specific modeling, even in healthy populations, may result in more physiologically plausible muscle fiber mechanics. Implementing subject-specific models may be especially beneficial when investigating populations with substantial geometric between-limb differences, or unilateral musculoskeletal pathologies, as these are not captured by a generic model.

PMID:35077508 | DOI:10.1371/journal.pone.0262936

PLoS One. 2022 Jan 25;17(1):e0262642. doi: 10.1371/journal.pone.0262642. eCollection 2022.

ABSTRACT

BACKGROUND: A growing body of evidence demonstrating that individuals with Non-Communicable Disease (NCD) are more likely to have severe forms of COVID-19 and subsequent mortality. Hence, our study aimed to assess the knowledge of vulnerability and preventive practices towards COVID-19 among patients with hypertension or diabetes in Southern Ethiopia.

OBJECTIVE: To assess the knowledge and preventive practices towards COVID-19 among patients with hypertension or diabetes mellitus in three zones of Southern Ethiopia, 2020.

METHODS: A community-based cross-sectional study design was used with a multi-stage random sampling technique to select 682 patients with hypertension or diabetes mellitus from 10th -17th July 2020 at the three zones of Southern Ethiopia. Logistic regression analysis with a 95% confidence interval was fitted to identify independent predictors of knowledge and preventive practices towards COVID-19. The adjusted odds ratio (AOR) was used to determine the magnitude of the association between the outcome and independent variables. P-value <0.05 is considered statistically significant.

RESULTS: The Multi-dimensional knowledge (MDK) analysis of COVID-19 revealed that 63% of study subjects had good knowledge about COVID-19. The overall preventive practice towards COVID -19 was 26.4%. Monthly income (AOR = 1.42; 95% CI: 1.04, 1.94) significantly predicted knowledge towards COVID-19. Ninety-five percent of the study subjects knew that the COVID-19 virus spreads via respiratory droplets of infected individuals. One hundred and ten (16.2%) of study subjects correctly responded to the questions that state whether people with the COVID-19 virus who do not have a fever can infect the other. Knowledge about COVID-19 (AOR = 1.47; 95% CI: 1.03, 2.1) became the independent predictor of preventive practice.

CONCLUSIONS: In this study, the knowledge of the respondents towards the COVID-19 pandemic was good. But the preventive practice was very low. There was a significant gap between knowledge and preventive practices towards the COVID-19 pandemic among the study subjects. Monthly income was significantly associated with knowledge of COVID-19. Knowledge of COVID-19 was found to be an independent predictor of preventive practice towards COVID-19. Community mobilization and improving COVID-19- related knowledge and practice are urgently recommended for those patients with hypertension or diabetes mellitus.

PMID:35077488 | DOI:10.1371/journal.pone.0262642