Miracle-dz/UniFAR-FTUs huggingface dataset:
Ecological restoration of ecosystems degraded by invasive alien plants in South African Fynbos: Is spontaneous succession a viable strategy?

Ecological restoration is a global imperative to reverse widespread habitat loss and degradation, including by invasive alien plants. In South Africa’s Core Cape Subregion, alien tree invasions are widespread and their control continues to be a major undertaking. As funding is limited, active restoration interventions are rarely implemented and the focus is on invader removal – the assumption being that ecosystems will self-repair. This paper reviews research findings from the past three decades to assess in which situations spontaneous succession is a viable strategy for restoring alien-invaded ecosystems. We found that ecosystems can self-repair, provided that key biotic and/or abiotic thresholds have not yet been crossed. Self-repair has been observed in many cases where dense invader stands with short residence times have been cleared and where diverse native plant growth forms survive, either in the above-ground vegetation or in soil seed banks. However, several factors influence this generalisation, including the identity of the invader, the ecosystem type, and the efficacy of alien control. Thresholds are crossed sooner with invasions of alien Acacia and Eucalyptus species than those of Hakea and Pinus species, resulting in lower potential for spontaneous recovery. Lowland fynbos ecosystems are less resilient to invasion, and have a lower capacity for self-repair, than mountain fynbos ecosystems. Poorly implemented alien plant control measures can result in a resurgence of the invader to the detriment of native species recovery. We outline some management principles for optimising spontaneous succession potential and integrating alien control and restoration interventions.
Approaches for molecular identification and typing of the Cryptococcus species complex: an update

The Cryptococcus species complex is composed of two common pathogenic species, namely Cryptococcus neoformans and Cryptococcus gattii, which cause systemic infections in both immunocompromised and immunocompetent individuals. Both species have a bipolar mating system, with mating type (MAT&agr;) being predominant in clinical and environmental isolates. On the basis of genetic variation, this species complex is divided into eight major genotypes, which show differences in epidemiology, biology, virulence and antifungal susceptibility. Within each major genotype, more diverse subgroups have been discovered and could be related to specific pathogenic attributes. This review will discuss the methods that have been developed in recent years to characterize the MATs, genotypes, varieties, species and serotypes established previously in this microorganism.
Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease

Real-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21st Century Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N = 88,867) and IBM MarketScan Research Databases (N = 106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, beneficial against common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.
Face coverings and respiratory tract droplet dispersion

Respiratory droplets are the primary transmission route for SARS-CoV-2, a principle which drives social distancing guidelines. Evidence suggests that virus transmission can be reduced by face coverings, but robust evidence for how mask usage might affect safe distancing parameters is lacking. Accordingly, we set out to quantify the effects of face coverings on respiratory tract droplet deposition. We tested an anatomically realistic manikin head which ejected fluorescent droplets of water and human volunteers, in speaking and coughing conditions without a face covering, or with a surgical mask or a single-layer cotton face covering. We quantified the number of droplets in flight using laser sheet illumination and UV-light for those that had landed at table height at up to 2 m. For human volunteers, expiratory droplets were caught on a microscope slide 5 cm from the mouth. Whether manikin or human, wearing a face covering decreased the number of projected droplets by less than 1000-fold. We estimated that a person standing 2 m from someone coughing without a mask is exposed to over 10 000 times more respiratory droplets than from someone standing 0.5 m away wearing a basic single-layer mask. Our results indicate that face coverings show consistent efficacy at blocking respiratory droplets and thus provide an opportunity to moderate social distancing policies. However, the methodologies we employed mostly detect larger (non-aerosol) sized droplets. If the aerosol transmission is later determined to be a significant driver of infection, then our findings may overestimate the effectiveness of face coverings.
Frontline healthcare workers' knowledge and perception of COVID-19 and willingness to work during the pandemic in Nepal: a nationwide cross-sectional web-based study

Abstract Background The health sector's effectiveness during a pandemic primarily depends on the availability, knowledge, skills, perceptions, and motivations of frontline healthcare workers. In this study, we aimed to investigate the contextual factors associated with the knowledge, perceptions, and the willingness of frontline healthcare workers to work during the COVID-19 pandemic in Nepal. Methods A total of 1051 frontline health-workers from all seven Nepalese provinces were included in this web-based cross-sectional study, which was conducted in May 2020. Using a 5-point Likert scale questionnaire, we collected information on knowledge, perceptions, and the willingness of frontline healthcare workers to work during the COVID-19 pandemic. Multivariable logistic regression was applied to identify independent associations between predictors and outcome variables. Results Of the 1051 frontline health-workers, 17.2% were found to have inadequate knowledge on COVID-19, 63.6% reported unsatisfactory perceptions of government response, and 35.9% showed an unwillingness to work during the pandemic. Health workers at local health facilities (AOR: 0.35; 95% CI: 0.17-0.68) and those with chronic diseases were less likely to have adequate knowledge of COVID-19. Nurses (AOR: 2.10; 95% CI: 1.38-3.18), health-workers from Karnali Province (AOR: 2.62; 95% CI: 1.52-4.53), and those who had adequate knowledge of COVID-19 (AOR: 3.86; 95% CI: 2.51-6.16) were more likely to have satisfactory perception towards government response to COVID-19. In addition, laboratory-workers, health workers from Karnali province, and those with adequate knowledge (AOR: 1.81; 95% CI: 1.27-2.58) were more likely to work during the COVID-19 pandemic. Conclusions We concluded that frontline healthcare workers have some gaps in knowledge-related to COVID-19; about two-thirds of them had a negative perception of government response, and nearly one-third of them were unwilling to work. These observations demonstrate that prompt actions are required to improve health-worker knowledge of COVID-19, address negative perceptions to government responses, and motivate them to provide healthcare services during the pandemic. Keywords: COVID-19, Health-workers, Knowledge, Perception, Willingness
Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis

Objective. The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African Americans are disproportionally affected by SSc, yet underrepresented in research. The aim of this study was to comprehensively investigate the association of DNA methylation levels with SSc in dermal fibroblasts from patients of African ancestry. Methods. Reduced representation bisulfite sequencing (RRBS) was performed on primary cultured dermal fibroblasts from 15 SSc patients and 15 controls of African ancestry, and over 3.8 million CpG sites were tested for differential methylation patterns between cases and controls. Gene set enrichment (GSEA) and gene ontology (GO) analyses were computed to elucidate the underlying biological processes. Quantitative PCR (qPCR) was performed to assess correlations between DNA methylation changes and gene expression levels of top candidate genes. Results. Skin fibroblasts from African American patients exhibited widespread reduced DNA methylation. Differentially methylated CpG sites were most enriched in introns and intergenic regions, while depleted in 5' UTR, promoters, and CpG islands. Seventeen genes and eleven promoters showed significant differential methylation, mostly in non-coding RNA genes and pseudogenes. GSEA and GO enrichment analysis revealed enrichment of immune, metabolism, cell development, and cell signaling pathways, including those related to interferon signaling and mesenchymal differentiation. The hypomethylation of DLX5 and TMEM140 was accompanied by these genes' overexpression, while for the lncRNA MGC12916, it was accompanied by its under-expression in patients. Conclusion. These data show that differential methylation occurs in dermal fibroblasts from African American patients with SSc and identifies novel coding and non-coding genes.
Association between the Mediterranean diet and prostate cancer risk in a Greek population

Purpose Dietary modifications have been correlated with survival in several neoplasia, such as prostate cancer. The present study was designed to investigate the association between the Mediterranean diet and prostate cancer risk. Methods A retrospective analysis of patients with a high suspicion of suffering from prostate cancer (PCa) who underwent prostate biopsy was performed. According to histopathology, two groups were generated, the PCa group and the Healthy group. The dietary profile of our study population was implemented, based on a modified MDS (Mediterranean Diet Score) questionnaire. A logistic regression model was used for the interpretation of our data. Results In total, 431 patients with prostate cancer and 279 healthy men were included in our study. The demographic characteristics of the patients were comparable. Daily consumption of white meat (OR: 0.59), dairy products (OR: 0.64), nuts (OR: 0.63) and whole grains (OR: 0.55) was higher in healthy males. Infrequent consumption of vegetables was linked with an increased rate of PCa (OR: 2.55). Interestingly daily consumption of processed meat rates was higher in healthy men. However, a significant correlation between specific intake products or frequency and the incidence of PCa was not established. Conclusions Although, an association between the dietary patterns and PCa was not determined, components consumption patterns displayed a higher daily intake rate of white meat, dairy products, nuts and whole grains. Further prospective trials are required to validate the effect of Mediterranean diet in the incidence and mortality of PCa patients.
Hydrogen peroxide enhances antioxidative defense in the leaves of water caltrop (Trapa bicornis) seedlings treated with lead

Abstract Hydrogen peroxide (H2O2) plays versatile roles in various biological processes and in responses to stress in plants. To investigate effects of exogenous H2O2 on the transcript levels of some genes encoding antioxidative enzymes, such as superoxide dismutase Cu/Zn (Cu/ZnSOD), catalase (CAT) and ascorbate peroxidase (APX), and also on the ultrastructural alterations caused by lead, 7-day-old seedlings of water caltrop (Trapa bicornis) were treated with lead salt (0.05 mmol/L) separately, or combined with H2O2 (2.5 mmol/L). Ultrastructural observation on the mesophyll cells demonstrated that the lead toxicity, which resulted in the membrane instability and abnormal organization within organelles, was eliminated under the condition of the co-treatment with H2O2 and lead. In this relation the combined treatment with H2O2 and lead prevented the increased amount of malondialdehyde to some extent during the whole experimental period (24, 48, and 72 h). Furthermore, quantitative measurements by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the co-treatment with both compounds, in contrast to the lead treatment alone, significantly up-regulated transcripts of CAT, APX, and a lignin biosynthesis related gene encoding ferulate-5-hydroxylase (F5H). The H2O2-induced F5H expression is thought to modify cell wall and thus lower Pb entry into water caltrop seedlings, thereby enhancing tolerance to Pb stress. Morphological and molecular evidences in the present study perhaps reflect the fact that some antioxidative enzymes, especially CAT and APX, combined with the action of F5H on cell wall modification, contribute to the enhanced antioxidative defense in the examined plants treated with lead.
Comprehensive analysis of the key epidemiological parameters to evaluate the impact of BCG vaccination on COVID-19 pandemic

Globally, the heterogenous coronavirus disease 2019 (COVID-19) case fatality rate (CFR) could be influenced by various epidemiological parameters. Identifying these could help formulate effective public health strategies. Incidence and mortality of COVID-19 for each of the 220 countries as on July 30, 2020 were evaluated against key epidemiological variables, namely - BCG vaccination (ongoing vs. discontinued/never undertaken), %population aged [≥]65 years, incidences of ischemic heart disease (IHD), hypertensive heart disease (HHD), cancer, malaria, and diabetes; human development index (HDI) and population density. These were retrieved from the public domains of WHO, UN, World Bank and published reports. The COVID-19 CFRs ranged between 0.0% and 28.3% (mean {+/-} SD: 3.05% {+/-} 3.48). The influence of the individual epidemiological parameters on CFR were evaluated through the event rate estimations. A significantly lower event rate was observed in countries with ongoing BCG vaccination program (ER: with vs without ongoing BCG vaccination: 0.020 vs 0.034, p<0.001). The type of BCG strains used also influenced the ER; this being 0.018, 0.031 and 0.019 for early, late and mixed strains respectively (p=0.008). The epidemiological variables significantly associated with higher COVID-19 event rate were countries with higher %population aged [≥]65 years (p<0.001), greater incidence of IHD (p<0.001) and cancer (p=0.003) and better HDI (p=0.003). Incidences of malaria, HHD and diabetes along with population density had no significant impact on COVID-19 CFR. Further, BCG vaccination significantly lowered the COVID-19 ER in each of the high-risk population subgroups - countries with >7.1% population aged [≥]65 years (p=0.008), >0.737 HDI (p=0.001), IHD >1171/105 population (p=0.004) and cancer incidence >15726 (p<0.001). The results supports BCG induced trained immunity leading to heterologous immunoprotection against COVID-19. Thus BCG vaccination with early strains could provide a cost-effective prophylaxis, especially in high-risk individuals and bridge the gap till an effective vaccine against SARS-CoV-2 is freely available globally.
ASSOCIATION BETWEEN ETHNICITY AND SEVERE COVID-19 DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Background: Multiple reports suggested disproportionate impact of Covid-19 on ethnic minorities. Whether ethnicity is an independent risk factor for severe Covid-19 illness is unclear. Purpose: Review the association between ethnicity and poor Covid-19 outcomes including all-cause mortality, hospitalisation, critical care admission, respiratory and kidney failure. Data Sources: MEDLINE, EMBASE, Cochrane COVID-19 Study Register, WHO COVID-19 Global Research Database up to 15/06/2020, and preprint servers. No language restriction. Study Selection: All studies providing ethnicity-aggregated data on the pre-specified outcomes, except case reports or interventional trials Data Extraction: Pairs of investigators independently extracted data, assessed risk of bias using Newcastle-Ottawa scale (NOS), and rated certainty of evidence following GRADE framework. Data Synthesis: Seventy-two articles (59 cohort studies with 17,950,989 participants; 13 ecological studies; 54 US-based and 15 UK-based; 41 peer-reviewed) were included for systematic review and 45 for meta-analyses. Risk of bias was low, with median NOS of 7 (interquartile range 6-8). In the unadjusted analyses, compared to white ethnicity, all-cause mortality risk was similar in Black (RR:0.96 [95%CI: 0.83-1.08]), Asian (RR:0.99 [0.85-1.16]) but reduced in Hispanic ethnicity (RR:0.69 [0.57-0.84]). Age and sex-adjusted-risks were significantly elevated for Black (HR:1.38 [1.09-1.75]) and Asian (HR:1.42 [1.15-1.75]), but not for Hispanic (RR:1.14 [0.93-1.40]). Further adjusting for comorbidities attenuated these association to non-significance; Black (HR:0.95 [0.72-1.25]); Asian (HR:1.17 [0.84-1.63]); Hispanic (HR:0.94 [0.63-1.44]). Similar results were observed for other outcomes. In subgroup analysis, there is a trend towards greater disparity in outcomes for UK ethnic minorities, especially hospitalisation risks. Limitations: Paucity of evidence on native ethnic groups, and studies outside US and UK. Conclusions: Currently available evidence cannot confirm ethnicity as an independent risk factor for severe Covid-19 illness, but indicates that disparity may be partially attributed to greater burden of comorbidities. Registration: PROSPERO, CRD42020188421 Funding source: none
Alterations of Gut Microbiome in Tibetan Patients With Coronary Heart Disease

Coronary heart disease (CHD) is closely related to gut microbiota, which may be significantly affected by ethnicity and the environment. Knowledge regarding the gut microbiome of Tibetan CHD patients living in the Qinghai–Tibet Plateau is very limited. In this study, we characterized the physiological parameters and gut microbiota from 23 healthy Tibetans (HT), 18 CHD patients, and 12 patients with non-stenosis coronary heart disease (NCHD). We analyzed the alterations of the gut microbiome in CHD patients and investigated the relationship between these alterations and the pathological indicators. We found no changes in trimethylamine N-oxide, however, a significant increase in lipopolysaccharides and white blood cells, and a decrease in high-density lipoprotein were observed in the blood of CHD patients, compared to that in the HT group. The gut microbiota of the NCHD group had a significantly higher Shannon index than that of the HT group. Adonis analysis showed that both microbial compositions and functions of the three groups were significantly separated. The Dialister genus was significantly lower and Blautia, Desulfovibrio, and Succinivibrio were significantly higher in abundance in CHD patients compared with the HT group, and the changes were significantly correlated with physiological indexes, such as increased lipopolysaccharides. Moreover, enrichment of genes decreased in four pathways of amino acid metabolism, such as arginine biosynthesis and histidine metabolism, although two lipid metabolism pathways, including fatty acid degradation and arachidonic acid metabolism, increased in the CHD group. Additionally, occupation and a family history of CHD were shown to be risk factors and affected the gut microbiota in Tibetans. Our study will provide insights into the understanding of CHD, leading to better diagnosis and treatment of Tibetan patients.
Influence of the maternal high-intensity-interval-training on the cardiac Sirt6 and lipid profile of the adult male offspring in rats

The susceptibility to cardiovascular disease in offspring could be reduced prior to birth through maternal intervention, before and during pregnancy. We evaluated whether the initiation periods of maternal exercise in preconception and pregnancy periods induce beneficial effects in the adult male offspring. Thirty-two female rats were divided into control and exercise groups. The exercise groups involve exercise before pregnancy or the preconception periods, exercise during pregnancy, and exercise before and during pregnancy. The mothers in the exercise groups were run on the treadmill in different periods. Then the birth weight and weekly weight gain of male offspring were measured, and the blood and left ventricle tissue of samples were collected for analysis of the Sirtuin 6 (Sirt6) and insulin growth factor-2 (IGF-2) gene expression, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (Cho), and triglycerides (TG). There was no significant difference in the birth weight of offspring groups (P = 0.246) while maternal HIIT only during pregnancy leads to reduce weekly weight gain of offspring. Our data showed that Sirt6 and IGF-2 gene expression was increased (P = 0.017) and decreased (P = 0.047) by maternal exercise prior to and during pregnancy, respectively. Also, the serum level of LDL (p = 0.002) and Cho (P = 0.007) were significantly decreased and maternal exercise leads to improves the running speed of the adult male offspring (p = 0.0176). This study suggests that maternal HIIT prior to and during pregnancy have positive intergenerational consequence in the health and physical readiness of offspring.
Development of thrombocytopenia is associated with improved survival in patients treated with immunotherapy

Background: Immune-related adverse events are associated with efficacy of immune checkpoint inhibitors (ICIs). We hypothesize that immune-mediated thrombocytopenia could be a biomarker for response to ICIs. Materials & methods: This retrospective study included 215 patients with metastatic malignancies treated with ICIs. Patients were stratified by nadir platelet count. Outcomes of interest were progression-free survival and overall survival. Results: On multivariate analysis, grade 1 thrombocytopenia was positively associated with overall survival compared with patients who did not develop thrombocytopenia (hazard ratio [HR]= 0.28 [95% CI: 0.13–0.60]; p = 0.001), while grade 2–4 thrombocytopenia was not (HR= 0.36 [95% CI: 0.13–1.04]; p = 0.060). There was no association between degree of thrombocytopenia and progression-free survival. Conclusion: Follow-up studies are warranted to substantiate the predictive significance of thrombocytopenia in patients receiving ICIs.