Nevin Manimala

Clin Exp Dermatol. 2021 Apr 19. doi: 10.1111/ced.14697. Online ahead of print.

ABSTRACT

Systemic photoprotection aims to negate the negative effects of ultraviolet radiation-induced DNA damage. Systemic supplements might be used as a monotherapy or in combination with topical sunscreens. Using the keywords ‘carotenoids,’ ‘flavonoids,’ ‘systemic photoprotection,’ ‘polyphenols’ and ‘polypodium leucotomos extract,” we searched the databases MEDLINE and EMBASE to find relevant English-language articles. Few trials have supported the use of any of these supplements as a monotherapy, impeding the recommendation of these systemic supplements as an alternative to sunscreen for photoprotection. Nicotinamide has exhibited clinically relevant benefits in reducing non-melanoma skin cancers in trials and could be recommended as an adjunctive therapy in those most vulnerable. Further research is required that is of higher statistical power, using more clinically meaningful outcome measures with comparison to the current gold standard of care, topical photoprotection, to support the use of alternative therapies in clinical practice.

PMID:33872410 | DOI:10.1111/ced.14697

Int Endod J. 2021 Apr 19. doi: 10.1111/iej.13531. Online ahead of print.

ABSTRACT

AIM: To record the prevalence of a priori power calculations in the manuscripts published in three endodontic journals between 2018 and 2020 and detect further associations with a number of study characteristics including journal, publication year, study design, geographic region, number of centres and authors, whether the primary outcome pertained to a statistically significant effect and whether Confidence Intervals (CIs) were reported.

METHODOLOGY: The contents of the three leading endodontic journals with the highest impact factor (International Endodontic Journal, IEJ; Journal of Endodontics, JOE; and Australian Endodontic Journal, AEJ) were assessed from January 2018 to December 2020. The proportion of articles reporting a priori power calculations were recorded, and relevant associations as described above were assessed. Univariable and multivariable logistic regression were used to identify significant predictors, while interaction and linear trend effects were also considered.

RESULTS: A total of 716 original research articles were included. The vast majority were published in the JOE (417/716; 58.2%), followed by the IEJ (225/716; 31.4%) and the AEJ (74/716; 10.4%). Overall, a priori power considerations were reported in 243 out of 716 articles (33.9%). The IEJ presented 1.61 times higher odds for including a priori power considerations compared to JOE (adjusted Odds Ratio, OR=1.61; 95%CI: 1.11, 2.34), while for the AEJ, the corresponding odds were 41% lower in comparison to JOE (adjusted OR= 0.59; 95%CI: 0.31, 1.14). For each additional year indicating more recent publication, the odds for adopting appropriate reporting practices for power considerations were increased by 64% (adjusted OR= 1.64; 95CIs: 1.32, 2.04). There was strong evidence that interventional research was associated with 10.54 times higher odds for a priori considerations compared to observational study design (adjusted OR= 10.54; 95%CIs: 5.50, 20.19).

CONCLUSIONS: The high prevalence of failure to include a priori power considerations was indicative of suboptimal reporting in endodontic research, in the three endodontic journals analysed. Although the condition improved over time, efforts to incorporate a correct determination of the required sample size at the design stage for any future study should be endorsed by journal editors, authors and the scientific community.

PMID:33872405 | DOI:10.1111/iej.13531

PLoS One. 2021 Apr 19;16(4):e0250247. doi: 10.1371/journal.pone.0250247. eCollection 2021.

ABSTRACT

This paper aims to identify the regional potential of Industry 4.0 (I4.0). Although the regional background of a company significantly determines how the concept of I4.0 can be introduced, the regional aspects of digital transformation are often neglected with regard to the analysis of I4.0 readiness. Based on the analysis of the I4.0 readiness models, the external regional success factors of the implementation of I4.0 solutions are determined. An I4.0+ (regional Industry 4.0) readiness model, a specific indicator system is developed to foster medium-term regional I4.0 readiness analysis and foresight planning. The indicator system is based on three types of data sources: (1) open governmental data; (2) alternative metrics like the number of I4.0-related publications and patent applications; and (3) the number of news stories related to economic and industrial development. The indicators are aggregated to the statistical regions (NUTS 2), and their relationships analyzed using the Sum of Ranking Differences (SRD) and Promethee II methods. The developed I4.0+ readiness index correlates with regional economic, innovation and competitiveness indexes, which indicates the importance of boosting regional I4.0 readiness.

PMID:33872343 | DOI:10.1371/journal.pone.0250247

PLoS One. 2021 Apr 19;16(4):e0250344. doi: 10.1371/journal.pone.0250344. eCollection 2021.

ABSTRACT

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities’ abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera’s abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

PMID:33872339 | DOI:10.1371/journal.pone.0250344

PLoS Pathog. 2021 Apr 19;17(4):e1009522. doi: 10.1371/journal.ppat.1009522. Online ahead of print.

ABSTRACT

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, PDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.

PMID:33872331 | DOI:10.1371/journal.ppat.1009522

PLoS One. 2021 Apr 19;16(4):e0249853. doi: 10.1371/journal.pone.0249853. eCollection 2021.

ABSTRACT

BACKGROUND: Knowledge, attitudes, perception, and preventative practices regarding coronavirus- 2019 (COVID-19) are crucial in its prevention and control. Several studies have noted that the majority of people in sub-Saharan African are noncompliant with proposed health and safety measures recommended by the World Health Organization (WHO) and respective country health departments. In most sub-Saharan African countries, noncompliance is attributable to ignorance and misinformation, thereby raising questions about people’s knowledge, attitudes, perception, and practices towards COVID-19 in these settings. This situation is particularly of concern for governments and public health experts. Thus, this scoping review is aimed at mapping evidence on the knowledge, attitudes, perceptions, and preventive practices (KAP) towards COVID-19 in sub-Saharan Africa (SSA).

METHODS: Systematic searches of relevant articles were performed using databases such as the EBSCOhost, PubMed, Science Direct, Google Scholar, the WHO library and grey literature. Arksey and O’Malley’s framework guided the study. The risk of bias for included primary studies was assessed using the Mixed Method Appraisal Tool (MMAT). NVIVO version 10 was used to analyse the data and a thematic content analysis was used to present the review’s narrative account.

RESULTS: A total of 3037 eligible studies were identified after the database search. Only 28 studies met the inclusion criteria after full article screening and were included for data extraction. Studies included populations from the following SSA countries: Ethiopia, Nigeria, Cameroon, Uganda, Rwanda, Ghana, Democratic Republic of Congo, Sudan, and Sierra Leone. All the included studies showed evidence of knowledge related to COVID-19. Eleven studies showed that participants had a positive attitude towards COVID-19, and fifteen studies showed that participants had good practices towards COVID-19.

CONCLUSIONS: Most of the participants had adequate knowledge related to COVID-19. Despite adequate knowledge, the attitude was not always positive, thereby necessitating further education to convey the importance of forming a positive attitude and continuous preventive practice towards reducing contraction and transmission of COVID-19.

PMID:33872330 | DOI:10.1371/journal.pone.0249853

PLoS Negl Trop Dis. 2021 Apr 19;15(4):e0007944. doi: 10.1371/journal.pntd.0007944. Online ahead of print.

ABSTRACT

Rabies is a vaccine-preventable fatal zoonotic disease. Uganda, through the veterinary surveillance system at National Animal Disease Diagnostics and Epidemiology Centre (NADDEC), captures animal bites (a proxy for rabies) on a monthly basis from districts. We established trends of incidence of animal bites and corresponding post-exposure prophylactic anti-rabies vaccination in humans (PEP), associated mortality rates in humans, spatial distribution of animal bites, and pets vaccinated during 2013-2017. We reviewed rabies surveillance data at NADDEC from 2013-2017. The surveillance system captures persons reporting bites by a suspected rabid dog/cat/wild animal, human deaths due to suspected rabies, humans vaccinated against rabies, and pets vaccinated. Number of total pets was obtained from the Uganda Bureau of Statistics. We computed incidence of animal bites and corresponding PEP in humans, and analyzed overall trends, 2013-2017. We also examined human mortality rates and spatial distribution of animal bites/rabies and pets vaccinated against rabies. We identified 8,240 persons reporting animal bites in Uganda during 2013-2017; overall incidence of 25 bites/ 100,000population. The incidence significantly decreased from 9.2/100,000 in 2013 to 1.3/100,000 in 2017 (OR = 0.62, p = 0.0046). Of the 8,240 persons with animal bites, 6,799 (82.5%) received PEP, decreasing from 94% in 2013 to 71% in 2017 (OR = 0.65, p<0.001). Among 1441 victims, who reportedly never received PEP, 156 (11%) died. Western region had a higher incidence of animal bites (37/100,000) compared to other regions. Only 5.6% (124,555/2,240,000) of all pets in Uganda were vaccinated. There was a decline in the reporting rate (percentage of annual district veterinary surveillance reports submitted monthly to Commissioner Animal Health by districts) of animal bites. While reported animal bites by districts decreased in Uganda, so did PEP among humans. Very few pets received anti-rabies vaccine. Evaluation of barriers to complete reporting may facilitate interventions to enhance surveillance quality. We recommended improved vaccination of pets against rabies, and immediate administration of exposed humans with PEP.

PMID:33872314 | DOI:10.1371/journal.pntd.0007944

PLoS Genet. 2021 Apr 19;17(4):e1009455. doi: 10.1371/journal.pgen.1009455. Online ahead of print.

ABSTRACT

Expression quantitative trait loci (eQTL) studies are used to understand the regulatory function of non-coding genome-wide association study (GWAS) risk loci, but colocalization alone does not demonstrate a causal relationship of gene expression affecting a trait. Evidence for mediation, that perturbation of gene expression in a given tissue or developmental context will induce a change in the downstream GWAS trait, can be provided by two-sample Mendelian Randomization (MR). Here, we introduce a new statistical method, MRLocus, for Bayesian estimation of the gene-to-trait effect from eQTL and GWAS summary data for loci with evidence of allelic heterogeneity, that is, containing multiple causal variants. MRLocus makes use of a colocalization step applied to each nearly-LD-independent eQTL, followed by an MR analysis step across eQTLs. Additionally, our method involves estimation of the extent of allelic heterogeneity through a dispersion parameter, indicating variable mediation effects from each individual eQTL on the downstream trait. Our method is evaluated against other state-of-the-art methods for estimation of the gene-to-trait mediation effect, using an existing simulation framework. In simulation, MRLocus often has the highest accuracy among competing methods, and in each case provides more accurate estimation of uncertainty as assessed through interval coverage. MRLocus is then applied to five candidate causal genes for mediation of particular GWAS traits, where gene-to-trait effects are concordant with those previously reported. We find that MRLocus’s estimation of the causal effect across eQTLs within a locus provides useful information for determining how perturbation of gene expression or individual regulatory elements will affect downstream traits. The MRLocus method is implemented as an R package available at https://mikelove.github.io/mrlocus.

PMID:33872308 | DOI:10.1371/journal.pgen.1009455

PLoS One. 2021 Apr 19;16(4):e0248791. doi: 10.1371/journal.pone.0248791. eCollection 2021.

ABSTRACT

BACKGROUND AND PURPOSE: The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap.

METHODS: Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data.

RESULTS: The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism.

CONCLUSION: The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.

PMID:33872305 | DOI:10.1371/journal.pone.0248791

PLoS Comput Biol. 2021 Apr 19;17(4):e1008856. doi: 10.1371/journal.pcbi.1008856. Online ahead of print.

ABSTRACT

Convolutional Neural Networks (CNNs) are statistical models suited for learning complex visual patterns. In the context of Species Distribution Models (SDM) and in line with predictions of landscape ecology and island biogeography, CNN could grasp how local landscape structure affects prediction of species occurrence in SDMs. The prediction can thus reflect the signatures of entangled ecological processes. Although previous machine-learning based SDMs can learn complex influences of environmental predictors, they cannot acknowledge the influence of environmental structure in local landscapes (hence denoted “punctual models”). In this study, we applied CNNs to a large dataset of plant occurrences in France (GBIF), on a large taxonomical scale, to predict ranked relative probability of species (by joint learning) to any geographical position. We examined the way local environmental landscapes improve prediction by performing alternative CNN models deprived of information on landscape heterogeneity and structure (“ablation experiments”). We found that the landscape structure around location crucially contributed to improve predictive performance of CNN-SDMs. CNN models can classify the predicted distributions of many species, as other joint modelling approaches, but they further prove efficient in identifying the influence of local environmental landscapes. CNN can then represent signatures of spatially structured environmental drivers. The prediction gain is noticeable for rare species, which open promising perspectives for biodiversity monitoring and conservation strategies. Therefore, the approach is of both theoretical and practical interest. We discuss the way to test hypotheses on the patterns learnt by CNN, which should be essential for further interpretation of the ecological processes at play.

PMID:33872302 | DOI:10.1371/journal.pcbi.1008856