Nevin Manimala

Gigascience. 2022 Dec 28;12:giac126. doi: 10.1093/gigascience/giac126.

ABSTRACT

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) methods have been advantageous for quantifying cell-to-cell variation by profiling the transcriptomes of individual cells. For scRNA-seq data, variability in gene expression reflects the degree of variation in gene expression from one cell to another. Analyses that focus on cell-cell variability therefore are useful for going beyond changes based on average expression and, instead, identifying genes with homogeneous expression versus those that vary widely from cell to cell.

RESULTS: We present a novel statistical framework, scShapes, for identifying differential distributions in single-cell RNA-sequencing data using generalized linear models. Most approaches for differential gene expression detect shifts in the mean value. However, as single-cell data are driven by overdispersion and dropouts, moving beyond means and using distributions that can handle excess zeros is critical. scShapes quantifies gene-specific cell-to-cell variability by testing for differences in the expression distribution while flexibly adjusting for covariates if required. We demonstrate that scShapes identifies subtle variations that are independent of altered mean expression and detects biologically relevant genes that were not discovered through standard approaches.

CONCLUSIONS: This analysis also draws attention to genes that switch distribution shapes from a unimodal distribution to a zero-inflated distribution and raises open questions about the plausible biological mechanisms that may give rise to this, such as transcriptional bursting. Overall, the results from scShapes help to expand our understanding of the role that gene expression plays in the transcriptional regulation of a specific perturbation or cellular phenotype. Our framework scShapes is incorporated into a Bioconductor R package (https://www.bioconductor.org/packages/release/bioc/html/scShapes.html).

PMID:36691728 | DOI:10.1093/gigascience/giac126

Eur J Heart Fail. 2023 Jan 23. doi: 10.1002/ejhf.2781. Online ahead of print.

ABSTRACT

AIMS: The REDUCE-LAP II trial demonstrated adverse outcomes after interatrial shunt device (IASD) placement in heart failure with preserved ejection fraction (HFpEF) attributed to latent pulmonary vascular disease (PVD). We hypothesized that exercise-stress cardiovascular magnetic resonance (CMR) imaging could provide non-invasive characterisation of cardiac and pulmonary physiology for improved patient selection.

METHODS AND RESULTS: The HFpEF-Stress Trial prospectively enrolled 75 patients with exertional dyspnoea and diastolic dysfunction. Patients underwent rest and exercise-stress right heart catheterisation (RHC), echocardiography and CMR imaging. Pulmonary artery and capillary wedge pressures, cardiac index (CI) and vascular resistance (PVR) were calculated. Latent PVD was defined as increased PVR≥1.74 Wood-Units during exercise-stress. CMR assessed long axis strains (LAS) and filling volumes of all cardiac chambers. Right ventricular (RV) function was further quantified by stroke and peak flow volumes. Patients with latent PVD (n = 24) showed lower RV function (rest TAPSE, p = 0.010; stress RV LAS, p < 0.001) compared to patients without (n = 43). During exercise-stress, RV stroke and peak flow volumes (p < 0.001) were reduced and led to impaired left atrial (p = 0.040) and with a strong statistical trend to impaired ventricular (LV) filling (p = 0.098). This subsequently resulted in reduced LV-CI (p < 0.001) despite preserved LV systolic function (LV LAS p ≥ 0.255). The degree of RV dysfunction during exercise-stress best predicted latent PVD (RV peak flow, AUC rest 0.73 vs. stress 0.89, p = 0.004).

CONCLUSIONS: Latent PVD is a feature of HFpEF and is associated with impaired RV functional reserve, global diastolic filling and LV-CI. This can be quantified by CMR and used to identify patients likely to benefit from IASD implantation.

PMID:36691723 | DOI:10.1002/ejhf.2781

Nurs Manag (Harrow). 2023 Jan 24. doi: 10.7748/nm.2023.e2074. Online ahead of print.

ABSTRACT

BACKGROUND: Front-line nurses caring for patients with coronavirus disease 2019 (COVID-19) experience stressful and traumatic working conditions, which may affect their professional quality of life.

AIM: To identify the effect of COVID-19 on front-line nurses’ professional quality of life, specifically on their levels of compassion satisfaction, burnout and secondary traumatic stress.

METHOD: A descriptive, cross-sectional comparative design was adopted. Data collection tools included self-reported sociodemographic and work-related characteristics and the self-report Professional Quality of Life Scale (ProQOL). Questionnaires (n=200) were distributed by email to two groups of nurses working in a government hospital in Saudi Arabia: front-line nurses who cared for patients with COVID-19 in isolation units; and front-line nurses who cared for patients without COVID-19 in inpatient units.

RESULTS: Completed questionnaires were received from 167 respondents, a response rate of 84%. Moderate levels of compassion satisfaction, burnout and secondary traumatic stress were found regardless of respondents’ involvement in caring for patients with COVID-19. There was no statistically significant difference between the two groups in terms of compassion satisfaction, burnout and secondary traumatic stress.

CONCLUSION: The COVID-19 pandemic presents a new challenge for front-line nurses, necessitating appropriate interventions to avoid burnout and secondary traumatic stress.

PMID:36691712 | DOI:10.7748/nm.2023.e2074

Fundam Clin Pharmacol. 2023 Jan 23. doi: 10.1111/fcp.12873. Online ahead of print.

ABSTRACT

BACKGROUND: Previous estimates to meta-analyze administration error rates were limited by the high statistical heterogeneity, restricting their use.

OBJECTIVES: To investigate sources of heterogeneity in pooled administration error rates in hospitalized adults.

METHODS: We systematically searched scientific databases up to November 2017 for studies presenting error rates/relevant numerical data in hospitalized adults. We conducted separate meta-analyses for the numerators: One Medication Error (OME) (each dose can be correct or incorrect) and Total Number of Errors (TNE) (more than one error per dose could be counted), using the generic inverse variance with a 95%-confidence interval. Heterogeneity was assessed using the I² and Cochran’s Q test.

RESULTS: We meta-analyzed 33 studies. The global pooled analyses based on the OME and TNE numerators showed very high heterogeneity (I² =100%;p<0.00001). For each meta-analysis, subgroup analyses based on study characteristics (countries, wards, population, routes of administration, error detection methods, and medications) yielded results with consistently elevated heterogeneity. Beyond these characteristics, we stratified the studies according to the mean error prevalence level as the threshold. Based on the OME numerator, we identified two subgroups of low (0.15[0.13-0.17];I² =0%;p=0.43) and high (0.26[0.24-0.27];I² =38%;p=0.17) pooled prevalence rates, with controlled heterogeneity. Similarly, for the TNE numerator, we identified two subgroups of low (0.10[0.09-0.10];I² =0%;p=0.76) and high (0.28[0.27-0.29];I² =0%; p=0.89) pooled prevalence rates, with controlled heterogeneity. These subgroups differed regarding the denominators used: Total opportunities for errors versus others (doses, observations, administrations).

CONCLUSION: Calculation methods, specifically the denominator, seem a primary factor in explaining heterogeneity in error rates. Standardizing numerators, denominators, and definitions is necessary.

PMID:36691676 | DOI:10.1111/fcp.12873

J Trop Med. 2023 Jan 14;2023:2831175. doi: 10.1155/2023/2831175. eCollection 2023.

ABSTRACT

BACKGROUND: Food handlers should be screened periodically for intestinal parasitic infections, and they should be treated to reduce intestinal parasite transmission to consumers through contaminated foods and drinks. Therefore, this study aimed to assess the prevalence and associated risk factors of intestinal parasitic infection among food handlers in Woldia town, North-East Ethiopia.

METHOD: A community-basedcross-sectional study was conducted among food handlers in Woldia town, North-East Ethiopia. A structured questionnaire was used to collect sociodemographic characteristics and intestinal parasite-associated risk factors. Microscopic examination of a stool sample was performed using wet-mount and formol-ether concentration techniques. Data were analyzed using SPSS version 20.0 statistical software packages. Bivariate and multivariate analyses were performed to investigate the association between intestinal parasitic infections and associated risk factors. In all comparisons, P value <0.05 was considered as statistically significant.

RESULT: The overall prevalence of intestinal parasitic infection among food handlers in Woldia town was 14.3%. Six different intestinal parasites were detected. The majority of the parasites identified were helminthic infections 37/52 (71%). Ascaris lumbricoides was the most dominant parasite (7.7%), followed by E. histolytica/dispar (2.7%) and G. lamblia (1.4%). Multivariate logistic regression analysis showed that intestinal parasitic infection had a statistically significant association with food handlers’ habits of hand washing without soap after latrine use (P < 0.01), swimming habit (P=0.03), and using a common knife (P < 0.01).

CONCLUSION: This study revealed a relatively high prevalence of intestinal parasites among food handlers in Woldia town. Strict and standard hygienic and sanitary practices should be implemented by food handlers. Moreover, food handlers should be screened for intestinal parasitic infection, and health education should be given periodically.

PMID:36691674 | PMC:PMC9867574 | DOI:10.1155/2023/2831175

Sci Afr. 2023 Mar;19:e01519. doi: 10.1016/j.sciaf.2022.e01519. Epub 2023 Jan 2.

ABSTRACT

A Bayesian joint modeling approach to dynamic prediction of HIV progression and mortality allows individualized predictions to be made for HIV patients, based on monitoring of their CD4 counts. This study aims to provide predictions of patient-specific trajectories of HIV disease progression and survival. Longitudinal data on 254 HIV/AIDS patients who received ART between 2009 and 2014, and who had at least one CD4 count observed, were employed in a Bayesian joint model of disease progression. Different forms of association structure that relate the longitudinal CD4 biomarker and time to death were assessed; and predictions were averaged over the different models using Bayesian model averaging. The individual follow-up times ranged from 1 to 120 months, with a median of 22 months and IQR 7-39 months. The estimates of the association structure parameters from two of the three models considered indicated that the HIV mortality hazard at any time point is associated with the rate of change in the underlying value of the CD4 count. Model averaging the dynamic predictions resulted in only one of the hypothesized association structures having non-zero weight in almost all time points for each individual, with the exception of twelve patients, for whom other association structures were preferred at a few time points. The predictions were found to be different when we averaged them over models than when we derived them from the highest posterior weight model alone. The model with highest posterior weight for almost all time points for each individual gave an estimate of the association parameter of -0.02 implying that for a unit increase in the CD4 count, the hazard of HIV mortality decreases by a factor (hazard ratio) of 0.98. Functional status and alcohol intake are important contributing factors that affect the mean square root of CD4 measurements.

PMID:36691645 | PMC:PMC7614071 | DOI:10.1016/j.sciaf.2022.e01519

Educ Inf Technol (Dordr). 2023 Jan 19:1-26. doi: 10.1007/s10639-023-11585-z. Online ahead of print.

ABSTRACT

Despite the growing attention towards gamification in learning context, challenge-based gamification application has rarely been subjected to testing in education. In recognition of this void, and grounded on gamification principles, we developed Educhall web-based program. Drawing on self-determination theory, and flow theory the present study aims to explore how the application of this challenge-based gamified program in to learning process of students can increase students’ motivation, flow, and academic success through the generated competition and challenge. The study applied a random experimental research design within distance learning context with 30 university students of control group and 30 students of experimental group who used the Educhall application for one academic semester. In line with self-determination theory, it was statistically evidenced that application of challenge-based gamified learning method increased level of academic performance and overall motivation. Of the motivational sub factors, experimental group reported significantly higher confidence level and satisfaction towards the course. Furthermore, grounded on flow theory, the study showed that challenge-based gamified learning increased flow level of learners but not significantly which warrants further data collection and experimental research in future studies. Implications for research and practice are discussed.

PMID:36691635 | PMC:PMC9850335 | DOI:10.1007/s10639-023-11585-z

Cereb Circ Cogn Behav. 2023 Jan 7;4:100157. doi: 10.1016/j.cccb.2023.100157. eCollection 2023.

ABSTRACT

INTRODUCTION: In this follow-up study, cerebral microvascular formations termed ‘raspberries’ were quantified according to cerebral atherosclerosis (C-ASCL) and acute circulatory failure (ACF). We also examined the regional distribution of raspberries throughout the brain.

MATERIALS AND METHODS: The study population consisted of adult individuals who had undergone a diagnostic neuropathological autopsy. Groups were formed to examine the association between raspberries, C-ASCL and ACF (control group, C-ASCL group, C-ASCL+ACF group [n = 47 per group] and a combined C-ASCL-tot group [n = 94]). To examine the regional distribution, additional groups were formed based on previously known raspberry densities of the frontal cortex (high-, medium- and low-density group [n = 6 per group]). Raspberries were quantified on scanned haematoxylin-eosin-stained sections.

RESULTS: Cortical raspberry density did not differ at a statistically significant level between the control group, the C-ASCL group and the C-ASCL+ACF group (P = 0.10) but did so between the control group and the C-ASCL-tot group (P = 0.033). The total raspberry density of the high-, medium- and low-density groups differed at a statistically significant level (P = 0.005), which remained in group-to-group comparisons of the high- and medium-density groups (P = 0.015) and the high- and low-density groups (P = 0.002). Raspberries were rare in cerebral white matter and in the cerebellum.

CONCLUSION: An association between raspberry density and C-ASCL is supported but is weaker than previously indicated. An association with ACF is not indicated. The raspberry density of the frontal cortex provides an approximation of the brain’s total raspberry density.

PMID:36691600 | PMC:PMC9860404 | DOI:10.1016/j.cccb.2023.100157

BMJ Open. 2022 Sep 8;12(9):e055581. doi: 10.1136/bmjopen-2021-055581.

ABSTRACT

OBJECTIVES: This study aims to explore the spatial and spatiotemporal distribution of pertussis in Hunan Province, and provide a scientific basis for targeting preventive measures in areas with a high incidence of pertussis.

DESIGN: In this retrospective spatial and spatiotemporal (ecological) study, the surveillance and population data of Hunan Province from 2009 to 2019 were analysed. The ArcGIS V.10.3 software was used for spatial autocorrelation analysis and visual display, and SaTScan V.9.6 software was used for statistical analysis of spatiotemporal scan data.

SETTINGS: Confirmed and suspected pertussis cases with current addresses in Hunan Province and onset dates between 1 January 2009 and 31 December 2019 were included in the study.

PARTICIPANTS: The study used aggregated data, including 6796 confirmed and suspected pertussis cases.

RESULTS: The seasonal peak occurred between March and September, and scattered children were at high risk. The global Moran’s I was between 0.107 and 0.341 (p<0.05), which indicated that the incidence of pertussis in Hunan had a positive spatial autocorrelation. The results of local indicators of spatial autocorrelation analysis showed that the hot spots were mainly distributed in the northeast region of Hunan Province. Moreover, both purely space and spatiotemporal scans showed that the central and northeastern parts were the most likely cluster areas with an epidemic period between March and October in 2018 and 2019.

CONCLUSION: The distribution of the pertussis epidemic in Hunan Province from 2009 to 2019 shows spatiotemporal clustering. The clustering areas of the pertussis epidemic were concentrated in the central and northeastern parts of Hunan Province between March and October 2018 and 2019. In areas with low pertussis incidence, the strengthening of the monitoring system may reduce under-reporting. In areas with high pertussis incidence where we could study whether the genes of endemic pertussis strains are mutated and differ from vaccine strains.

PMID:36691220 | DOI:10.1136/bmjopen-2021-055581

BMJ Open. 2022 Sep 8;12(9):e058491. doi: 10.1136/bmjopen-2021-058491.

ABSTRACT

OBJECTIVE: To examine the association between area-level education and the local growth trajectories in antibacterial dispensing rates in Norwegian municipalities among children under 3 years old.

DESIGN: Retrospective, longitudinal study using individual primary care prescription data from the Norwegian Prescription Database for the period 2006-2016. Data were collected on the date of dispensing, the type and amount of antibiotic, the patient’s age, sex and municipality of residence and linked to municipality-level statistics on education available from Statistics Norway. We used multilevel growth curve modelling, with a linear trend variable modelled as a random effect and a cross-level interaction between linear trends and the proportion of the population in the municipality having received a university or college education.

SETTING: The local government level in Norway. The sample includes all municipalities over the study period.

OUTCOME MEASURE: Number of dispensed antibacterial prescriptions per 100 children in individual primary care by municipality and year.

RESULTS: We identified a significant negative linear trend in the square root of the dispensing rate for children under 3 years old during the period. This trend varied between municipalities. A negative cross-level interaction term between population education levels and random trends showed that municipalities with an average level of population education saw a reduction in their square root dispensing rates of -0.053 (95% CI -0.066 to -0.039) prescriptions per 100 children. Each additional percentage point in population education contributed a further -0.0034 (95% CI -0.006 to -0.001) reduction to the square root dispensing rate.

CONCLUSIONS: Municipalities in which a larger proportion of the local population have high educational achievements have been more successful in reducing antibacterial dispensing rates in children under 3 years old. Adopting area-level strategies and addressing local community disadvantages may help to optimise practices and prescribing patterns across local communities.

PMID:36691217 | DOI:10.1136/bmjopen-2021-058491