Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into Structures and Dynamics of Flavivirus Proteases from NMR Studies

Nuclear magnetic resonance (NMR) spectroscopy plays important roles in structural biology and drug discovery, as it is a powerful tool to understand protein structures, dynamics, and ligand binding under physiological conditions. The protease of flaviviruses is an attractive target for developing antivirals because it is essential for the maturation of viral proteins. High-resolution structures of the proteases in the absence and presence of ligands/inhibitors were determined using X-ray crystallography, providing structural information for rational drug design. Structural studies suggest that proteases from Dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV) exist in open and closed conformations. Solution NMR studies showed that the closed conformation is predominant in solution and should be utilized in structure-based drug design. Here, we reviewed solution NMR studies of the proteases from these viruses. The accumulated studies demonstrated that NMR spectroscopy provides additional information to understand conformational changes of these proteases in the absence and presence of substrates/inhibitors. In addition, NMR spectroscopy can be used for identifying fragment hits that can be further developed into potent protease inhibitors.
Primary school dropout : case of Chicualacuala, Mozambique

In 2004 Mozambique has made amazing efforts that opened up educational opportunities for many primary school children. According to Ministério da Educação (2012: 1), the number of children who enrolled in primary schools jumped from 1,5 million in 1992 to about 6 million in 2011. Despite these commendable efforts, many children drop out from primary schools after gaining initial access. As stated by the Ministério da Educação (2012: 57), the dropout rate in the country was over 10%. Thus, this study sought to delve into the reasons that lead primary school children to drop out from school and identify measures to curb the problem. To do so, a case study approach was used. Specifically, the study used in-depth interviews, focus group discussions and participant observation of behaviour in a single school in Chicualacuala. The study revealed that at least four categories of factors namely child-based-, household-based-, school-basedand community-based factors give rise to dropout. These factors were informed by the Bronfenbrenner ecological framework, which is the lens through which this study was conducted. Indeed, it was found that dropout was a process rather than a single event and almost always it had signs to predict its occurrence. In the light of these findings, the study gave a number of recommendations. These include enrolling children early, improving the performance of children, providing quality adult education, monitoring absenteeism appropriately, supporting orphans, convincing organisations that provide food for work support to tie this support to the
Transradial and transfemoral approach in patients treated with percutaneous coronary interventions and rotational atherectomy.

BACKGROUND The relationship between periprocedural complications and the type of vascular access in patients treated with percutaneous coronary intervention (PCI) and rotational atherectomy (RA) has not been as frequently investigated as in an overall group of patients treated with PCI. AIMS The aim of the current study was to assess the relationships between type of vascular access and selected periprocedural complications in a group of patients treated with PCI and RA. METHODS Based on a nationwide registry (ORPKI), we analysed 536 826 patients treated with PCI between 2014 and 2018. The study included 2 713 (0.5%) patients treated with PCI and RA; 1 018 (37.5%) patients were treated with femoral access, while 1 653 (60.9%) underwent radial access, and were later subjected to comparison. This comparison was proceeded by propensity score matching. RESULTS Following propensity score matching, multiple regression analysis revealed that patients treated with PCI from femoral access experienced coronary artery perforation significantly less frequently (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.08-0.92, P = 0.04). We did not observe any significant relationships concerning vascular access for periprocedural rate of death (P = 0.99), cardiac arrest (P = 0.41), puncture-site bleeding (P = 0.99), allergic reaction (P = 0.32), myocardial infarction (P = 0.48), no-reflow (P = 0.82) or the overall complication rate (P = 0.31). CONCLUSION Femoral access is related to lower rate of coronary artery perforations in comparison to radial access among patients treated with PCI and RA.
Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology

Abstract Background Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology (‘p’) factor. Methods Youth aged 8–16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. Results Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. Conclusions Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.
2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission

With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. ABSTRACT With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Author Video: An author video summary of this article is available.
The Oxidative Stress Markers of Horses—the Comparison with Other Animals and the Influence of Exercise and Disease

Simple Summary Although oxidative stress is detrimental in biological systems, direct analysis of the active oxygen species that causes the stress has been difficult at a clinical level. In the current study, we analyzed the levels of diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) in the serum of horses. These are easy to measure and they provide information on the level of oxidative stress in an animal. The mean d-ROM level in horses was higher than those in dogs or dairy cattle, and the levels in horses can be used to distinguish those with a disease. Abstract Diacron-reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP) levels in the serum of horses were measured (ponies, n = 15; thoroughbred, n = 31; other full-sized horses, n = 7). The mean d-ROM levels in horses were significantly higher (p < 0.001) than those in dairy cattle (n = 25) and dogs (n = 31). However, d-ROM levels in horses were lower than the standard levels reported in humans. When d-ROM and BAP levels were plotted graphically, the points for horses with a disease (ringbone in 1 Japanese sports horse, cellulitis in 1 thoroughbred, melanoma in 1 Lipizzaner) fell outside the group of points for other (non-diseased) horses. A similar separation was seen (using data from other authors) for a horse with Rhodococcus equi, a horse following castration surgery, and a mare following delivery. These results, comparing horses, other animals, and humans, are interesting from the standpoint of comparative medicine, and they contribute to the sparse literature available on d-ROM and BAP levels in animals. Because the level of d-ROM and BAP levels were changed depending on the situation of health, those indexes are promising as indices of health in horses.
International Prognostic Score for Asymptomatic Early-stage Chronic Lymphocytic Leukemia.

Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early stage disease and managed with active surveillance. The individual course of subjects with early stage CLL is heterogeneous and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in CLL patients with early, asymptomatic disease (IPS-E). Individual patient data from 11 international cohorts of patients with early stage CLL (n=4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated IGHV genes, absolute lymphocyte count >15 x109/l, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (one point each), and separated low-risk (score 0), intermediate-risk (score 1) and high-risk patients (score 2-3) showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The c-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk of treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.
Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs

Abstract Background Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery. Objectives To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor‐infiltrating regulatory T cells (Tregs), and intratumoral hypoxia. Animals Ninety‐two client‐owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma. Methods Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor‐2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia‐inducible factor (HIF)‐1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries. Results Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65‐0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF‐1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries. Conclusions and Clinical Importance Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.
Multimodal Assessment Increases Objective Identification of Hypersomnolence in Patients Referred for Multiple Sleep Latency Testing.

STUDY OBJECTIVES The multiple sleep latency test (MSLT) has limitations when evaluating disorders of hypersomnolence with unknown etiology. Alternative measures of hypersomnolence may objectively identify pathology in patients with complaints of daytime sleepiness that may not be captured by the MSLT alone. This study evaluated the impact of a multimodal hypersomnolence assessment relative to MSLT in patients with unexplained hypersomnolence. METHODS Seventy-five patients with unexplained hypersomnolence were included in the analyzed sample. Polysomnography was performed without prescribed wake time, and the psychomotor vigilance task (PVT) and pupillographic sleepiness test (PST) were completed between MSLT nap opportunities. Presence or absence of hypersomnolence for each assessment was defined using a priori cutpoints. Proportions of patients identified as hypersomnolent using the multimodal assessment relative to MSLT alone were evaluated, as well as the sensitivity and specificity of ancillary hypersomnolence measures relative to MSLT as a gold standard. RESULTS The multimodal assessment more than doubled the proportion of patients identified as having objective deficits relative to MSLT≤8 minutes alone. The combination of excessive sleep duration, lapses on the PVT, and impairments on PST also had perfect sensitivity in identifying all patients identified as sleepy by the MSLT across three different MSLT cutpoints (5, 8, and 10 minutes). CONCLUSIONS These data demonstrate the insufficiency of the MSLT as a singular tool to identify objective pathology in persons with unexplained hypersomnolence. Further efforts to refine and standardize multimodal assessments will likely improve diagnostic acumen and research into the causes of these disorders.
Mapping Quantitative Trait Loci onto Chromosome-Scale Pseudomolecules in Flax

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits. To date, a total of 313 QTL for 31 quantitative traits have been reported in 14 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, the scaffold sequences, or the pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but the most used ones were simple sequence repeats (SSRs) or single nucleotide polymorphisms (SNPs). To uniquely map the SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules, methods with several scripts and database files were developed to locate PCR- and SNP-based markers onto the same reference, co-locate QTL, and scan genome-wide candidate genes. Using these methods, 195 out of 200 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters; the candidate genes that co-located with these QTL clusters were also predicted. The methods and tools presented in this article facilitate marker re-mapping to a new reference, genome-wide QTL analysis, candidate gene scanning, and breeding applications in flax and other crops.
Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19. ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1. 2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection. IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.
Chitosan/Graphene Oxide Nanocomposite Membranes as Adsorbents with Applications in Water Purification

The scope of this article is to develop composite membranes using chitosan (CS) and graphene oxide (GO) as adsorbents for the removal of inorganic pollutants such as heavy metal ions, particularly Pb2+, from aqueous solutions. GO was obtained by modified Hummers method and blended with CS solution. The introduction of ethylenediaminetetraacetic acid (EDTA) compound to CS/GO suspension lead to an increased adsorption capacity of CS/GO for the elimination of heavy metals by forming stable chelates with them. The synthesized membranes were examined by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), and the adsorption behaviour of Pb2+ from aqueous solutions using CS/EDTA/GO membranes was evaluated using inductively coupled plasma mass spectrometry (ICP-MS). The adsorption performance of Pb2+ ions was studied by monitoring the concentration of Pb2+ against the adsorption period at an initial content of the adsorbent. The maximum adsorption efficiency of Pb2+ metal ions reached 767 mg·g−1 for CS/EDTA/GO 0.1%, 889 mg·g−1 for CS/EDTA/GO 0.3%, 970 mg·g−1 for CS/EDTA, 853 mg·g−1 for CS and 1526 mg·g−1 for GO. These findings show promising potential for CS/EDTA/GO membranes as effective adsorbent materials for the removal of heavy metal ions in water.
Micronutrient Dilution and Added Sugars Intake in U.S. Adults: Examining This Association Using NHANES 2009–2014

There is inconsistent evidence regarding the impact of added sugars consumption on micronutrient dilution of the diet. We examined the associations between added sugars intake deciles and nutrient adequacy for 17 micronutrients in U.S. adults 19+ (n = 13,949), 19–50 (n = 7424), and 51+ y (n = 6525) using two days of 24 hour dietary recall data from the National Health and Nutrition Examination Survey (NHANES) 2009–2014 and regression analysis. Added sugars intake deciles ranged from <3.8 to >23.3% of calories among adults 19+ y, with a median intake of 11.0% of calories. Significant associations (p ≤ 0.01) between added sugars intake deciles and percentage of the population below the Estimated Average Requirement (EAR) were found for magnesium, vitamin C, vitamin D, and vitamin E; only the association with magnesium remained significant after dropping the two highest and lowest deciles of intake, suggesting a threshold effect. Intakes below approximately 18% of calories from added sugars were generally not associated with micronutrient inadequacy. However, even at the lower deciles of added sugars, large percentages of the population were below the EAR for these four micronutrients, suggesting that adequate intakes are difficult to achieve regardless of added sugars intake.
Differences in clinical characteristics and outcome of de novo heart failure compared to acutely decompensated chronic heart failure – systematic review and meta-analysis

Abstract Background Recent evidence showed that the characteristics and outcome of those with de novo heart failure (HF) and acutely decompensated chronic heart failure (ADCHF) were different. We aimed to perform a comprehensive search on the clinical characteristics and outcome of patients with de novo HF and ADCHF. Methods We performed a comprehensive search on de novo/new onset acute HF vs ADCHF from inception up until December 2019. Results There were 38320 patients from 15 studies. De novo HF were younger and, had less prevalent hypertension, diabetes mellitus, ischaemic heart disease, chronic obstructive pulmonary disease, atrial fibrillation, and history of stroke/transient ischaemic attack compared to ADCHF. Five studies showed a lower NT-proBNP in de novo HF patients, while one study showed no difference. Valvular heart disease as aetiology of heart failure was less frequent in de novo HF, and upon sensitivity analysis, hypertensive heart disease was more frequent in de novo HF. As for precipitating factors, ACS (OR 2.42; I2:89%) was more frequently seen in de novo HF, whereas infection was less frequently (OR 0.69; I2:32%) in ADCHF. De novo HF was associated with a significantly lower 3-month mortality (OR 0.63; I2:91%) and 1-year (OR 0.59; I2:59%) mortality. Meta-regression showed that 1-year mortality did not significantly vary with age (p = .106), baseline ejection fraction (p = .703), or HF reduced ejection fraction (p = .262). Conclusion Risk factors, aetiology, and precipitating factors of HF in de novo and ADCHF differ. De novo HF also had lower 1-year mortality and 3-month mortality compared to ADCHF.