Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasmacytoid Dendritic Cells Mediate Control of Ross River Virus Infection via a Type I Interferon-Dependent, MAVS-Independent Mechanism

Arthritogenic alphaviruses, including Ross River virus (RRV), are human pathogens that cause debilitating acute and chronic musculoskeletal disease and are a significant public health burden. Using an attenuated RRV with enhanced susceptibility to host innate immune responses has revealed key cellular and molecular mechanisms that can mediate control of attenuated RRV infection and that are evaded by more virulent RRV strains. ABSTRACT Ross River virus (RRV) is a mosquito-borne alphavirus that causes epidemics of debilitating musculoskeletal disease. To define the innate immune mechanisms that mediate control of RRV infection, we studied a RRV strain encoding 6 nonsynonymous mutations in nsP1 (RRV-T48-nsP16M) that is attenuated in wild-type (WT) mice and Rag1−/− mice, which are unable to mount adaptive immune responses, but not in mice that lack the capacity to respond to type I interferon (IFN) (Ifnar1−/− mice). Utilizing this attenuated strain, our prior studies revealed that mitochondrial antiviral signaling (MAVS)-dependent production of type I IFN by Ly6Chi monocytes is critical for control of acute RRV infection. Here, we infected Mavs−/− mice with either WT RRV or RRV-T48-nsP16M to elucidate MAVS-independent protective mechanisms. Mavs−/− mice infected with WT RRV developed severe disease and succumbed to infection, whereas those infected with RRV-T48-nsP16M exhibited minimal disease signs. Mavs−/− mice infected with RRV-T48-nsP16M had higher levels of systemic type I IFN than Mavs−/− mice infected with WT virus, and treatment of Mavs−/− mice infected with the attenuated nsP1 mutant virus with an IFNAR1-blocking antibody resulted in a lethal infection. In vitro, type I IFN expression was induced in plasmacytoid dendritic cells (pDCs) cocultured with RRV-infected cells in a MAVS-independent manner, and depletion of pDCs in Mavs−/− mice resulted in increased viral burdens in joint and muscle tissues, suggesting that pDCs are a source of the protective IFN in Mavs−/− mice. These data suggest that pDC production of type I IFN through a MAVS-independent pathway contributes to control of RRV infection. IMPORTANCE Arthritogenic alphaviruses, including Ross River virus (RRV), are human pathogens that cause debilitating acute and chronic musculoskeletal disease and are a significant public health burden. Using an attenuated RRV with enhanced susceptibility to host innate immune responses has revealed key cellular and molecular mechanisms that can mediate control of attenuated RRV infection and that are evaded by more virulent RRV strains. In this study, we found that pDCs contribute to the protective type I interferon response during RRV infection through a mechanism that is independent of the mitochondrial antiviral signaling (MAVS) adaptor protein. These findings highlight a key innate immune mechanism that contributes to control of alphavirus infections.
Correlation analysis of upper airway morphology in patients with obstructive sleep apnea and anatomically small retruded mandibles

ABSTRACT Objective To investigate the relationship between upper airway morphology and the severity of obstructive sleep apnea (OSA) in patients with anatomically small retruded mandibles. Methods Fifty-two patients with small retruded mandibles underwent polysomnography and airway computed tomography. The airway morphology parameters and sleep assessment were compared between the patients with or without OSA. Results Twenty-eight patients diagnosed with OSA, according to polysomnography, had a higher distance between the hyoid bone and mandibular plane (HMP), lateral dimension (LAT)/anteroposterior dimension (AP), but lower minimum cross-sectional area (mCSA), AP, surface area, volume, avgCSA, and airway uniformity (U). The apnea-hypopnea index had negative correlations with mCSA, AP, surface area, volume, avgCSA, and U, and had a positive correlation with HMP and LAT/AP. Conclusion OSA is common among patients with small retruded mandibles and is associated with a more compressed upper airway shape and longer HMP.
Pravastatin‐induced changes in expression of long non‐coding and coding RNAs in endothelial cells

Atherosclerosis is the main cause of the cardiovascular disease (CVD). Elevated blood cholesterol and inflammation of the endothelium are two major mechanisms contributing to the establishment of atherosclerotic plaques. Statins, such as pravastatin, are blood‐cholesterol lowering drugs commonly prescribed for patients with or at risk for CVDs. In addition to lowering blood cholesterols, statins have recently been shown to improve endothelial function in both hyper‐ and normocholesterolemic patients with atherosclerosis. To understand the molecular mechanisms underlying the endothelial function improvement by statins, we assessed the RNA profile of pravastatin‐treated endothelial cells, particularly their mRNAs and long non‐coding RNAs (lncRNAs).
Incorporating Nonextractable Atrazine Residues into Soil Size Fractions as a Function of Time

Soil organic matter is directly implicated in pesticide nonextractable (bound) residues formation, but the role of different soil organic constituents is unknown. Physical soil fractionation allows separation, with minimal chemical modification, of organic constituents whose nature and properties are dependent on particle size. Physical fractionation was used to determine the role of soil organic constituents in atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) bound residues formation. 14 C-ring-labeled atrazine was applied to the top of soil lysimeters (0.3 by 1.2 m) in the field. The lysimeters were periodically removed during 16 mo, and the soil was physically fractionated into seven size fractions by sieving, sedimentation, and centrifugation : >200, 50 to 200, 20 to 50, 5 to 20, 2 to 5, 0.2 to 2, and 50 μm, those rich in nonhumified organic matter. The low capacity of humified organic matter in the finest size fractions to form bound residues is presumably due to the chemical nature of the humified organic matter ; however, accessibility of organic compounds stabilized on the fine mineral surfaces or included in aggregates structures is also a possibility. The most stable bound residues are associated with humified organic matter, especially in clay size fraction (0.2-2 μm). Physical soil fractionation as a function of incubation time allows definition of the different capacity of soil organic constituents to form bound residues in relation to their localization in the size fractions.
Simultaneous bilateral pulmonary resection via single‐utility port VATS for multiple pulmonary nodules: A single‐center experience of 16 cases

The detection rate of bilateral multiple pulmonary nodules (BMPNs) is increasing due to widespread use of chest computed tomography (CT) screening. However, there is no consensus on the treatment options for BMPNs and whether simultaneous bilateral pulmonary resection is safe remains controversial. The purpose of this study was to evaluate the feasibility and safety of simultaneous bilateral pulmonary resection for BMPNs.
Therapeutic Potential of TLR8 Agonist GS‐9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators

GS‐9688 (selgantolimod) is a toll‐like receptor 8 agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity of GS‐9688 has previously been evaluated in vitro in HBV‐infected hepatocytes and in vivo in the woodchuck model of CHB. Here we evaluated the potential of GS‐9688 to boost responses contributing to viral control and to modulate regulatory mediators.
Cash transfers and child nutritional outcomes: a systematic review and meta-analysis

Background Cash transfer (CT) programmes are implemented widely to alleviate poverty and provide safety nets to vulnerable households with children. However, evidence on the effects of CTs on child health and nutrition outcomes has been mixed. We systematically reviewed evidence of the impact of CTs on child nutritional status and selected proximate determinants. Methods We searched articles published between January 1997 and September 2018 using Agris, Econlit, Eldis, IBSS, IDEAS, IFPRI, Google Scholar, PubMed and World Bank databases. We included studies using quantitative impact evaluation methods of CTs with sample sizes over 300, targeted to households with children under 5 years old conducted in countries with gross domestic product per capita below US$10 000 at baseline. We conducted meta-analysis using random-effects models to assess the impact of CT programmes on selected child nutrition outcomes and meta-regression analysis to examine the association of programme characteristics with effect sizes. Results Out of 2862 articles identified, 74 articles were eligible for inclusion. We find that CTs have significant effects of 0.03±0.03 on height-for-age z-scores (p<0.03) and a decrease of 2.1% in stunting (95% CI −3.5% to −0.7%); consumption of animal-source foods (4.5%, 95% CI 2.9% to 6.0%); dietary diversity (0.73, 95% CI 0.28 to 1.19) and diarrhoea incidence (−2.7%, 95% CI −5.4% to −0.0%; p<0.05). The effects of CTs on weight-for-age z-scores and wasting were not significant (0.02, 95% CI −0.03 to 0.08; p<0.42) and (1.2%, 95% CI: −0.1% to 2.5%; p<0.07), respectively. We found that specific programme characteristics differentially modified the effect on the nutrition outcomes studied. Conclusion We found that CT programmes targeted to households with young children improved linear growth and contributed to reduced stunting. We found that the likely pathways were through increased dietary diversity, including through the increased consumption of animal-source foods and reduced incidence of diarrhoea. With heightened interest in nutrition-responsive social protection programmes to improve child nutrition, we make recommendations to inform the design and implementation of future programmes.
Exploring perceived occupational balance in women with fibromyalgia. A descriptive study

Abstract Background People with chronic pain conditions such as fibromyalgia may experience occupational limitations and imbalances in their basic and instrumental occupations of daily living, leisure, work, and social participation. Objective To describe occupational balance in persons with fibromyalgia and to analyze whether it is associated with self-reported disability and self-efficacy to manage symptoms. Methods A cross-sectional study was carried out. Individuals with fibromyalgia were invited to participate. Occupational balance was assessed with the Occupational Balance Questionnaire; self-reported disability was assessed with the World Health Organization Disability Assessment Schedule, WHODAS 2.0-12; and self-efficacy was evaluated with the 8-item version of the Arthritis Self-Efficacy Scale. Data were analyzed using multiple linear regression with a forward stepwise procedure. Results One hundred women with fibromyalgia were included. Occupational balance was 26.96 ± 12.09; however, scores differed between the mild disability group and the moderate disability group (33.11 ± 9.99 vs. 20.29 ± 10.61, p < 0.001). Multiple linear regression analyses revealed that self-reported disability and self-reported pain management explained 58.1% of the variance in occupational balance. Conclusion Women with fibromyalgia showed low occupational balance. Self-reported disability and self-reported pain management were associated with occupational balance. Significance Occupational therapy practitioners can design intervention programs focussing on occupational balance and self-efficacy to manage symptoms.
SARS-CoV-2 serosurveillance in a patient population reveals differences in virus exposure and antibody-mediated immunity according to host demography and healthcare setting.

Identifying drivers of SARS-CoV-2 exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient sera showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralisation assays showed that around half of individuals who tested positive by ELISA assay, developed highly neutralising antibodies, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, males and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralisation activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves.
Gene tree estimation error with ultraconserved elements: An empirical study on Pseudapis bees.

Summarizing individual gene trees to species phylogenies using two-step coalescent methods is now a standard strategy in the field of phylogenomics. However, practical implementations of summary methods suffer from gene tree estimation error, which is caused by various biological and analytical factors. Greatly understudied is the choice of gene tree inference method and downstream effects on species tree estimation for empirical data sets. To better understand the impact of this method choice on gene and species tree accuracy, we compare gene trees estimated through four widely used programs under different model-selection criteria: PhyloBayes, MrBayes, IQ-Tree and RAxML. We study their performance in the phylogenomic framework of > 800 ultraconserved elements from the bee subfamily Nomiinae (Halictidae). Our taxon sampling focuses on the genus Pseudapis, a distinct lineage with diverse morphological features, but contentious morphology-based taxonomic classifications and no molecular phylogenetic guidance. We approximate topological accuracy of gene trees by assessing their ability to recover two uncontroversial, monophyletic groups, and compare branch lengths of individual trees using the stemminess metric (the relative length of internal branches). We further examine different strategies of removing uninformative loci and the collapsing of weakly supported nodes into polytomies. We then summarize gene trees with ASTRAL and compare resulting species phylogenies, including comparisons to concatenation-based estimates. Gene trees obtained with the reversible jump model search in MrBayes were most concordant on average and all Bayesian methods yielded gene trees with better stemminess values. The only gene tree estimation approach whose ASTRAL summary trees consistently produced the most likely correct topology, however, was IQ-Tree with automated model designation (MFP). We discuss these findings and provide practical advice on gene tree estimation for summary methods. Lastly, we establish the first phylogeny-informed classification for Pseudapis s. l. and map the distribution of distinct morphological features of the group.
Biogenesis of large dense core vesicles in mouse chromaffin cells

Large dense core vesicle (LDCVs) biogenesis in neuroendocrine cells involves: (a) production of cargo peptides processed in the Golgi; (b) fission of cargo loaded LDCVs undergoing maturation steps; (c) movement of these LDCVs to the plasma membrane. These steps have been resolved over several decades in PC12 cells and in bovine chromaffin cells. More recently, the molecular machinery involved in LDCV biogenesis has been examined using genetically modified mice, generating contradictory results. To address these contradictions, we have used NPY‐mCherry electroporation combined with immunolabeling and super‐resolution structured illumination microscopy. We show that LDCVs separate from an intermediate Golgi compartment, mature in its proximity for about 1 hour and then travel to the plasma membrane. The exocytotic machinery composed of vSNAREs and synaptotagmin1, which originate from either de novo synthesis or recycling, is most likely acquired via fusion with precursor vesicles during maturation. Finally, recycling of LDCV membrane protein is achieved in less than 2 hours. With this comprehensive scheme of LDCV biogenesis we have established a framework for future studies in mouse chromaffin cells.
Association between thrombotic microangiopathy and activated alternative complement pathway in malignant nephrosclerosis.

BACKGROUND Malignant nephrosclerosis, defined as renal microangiopathy in the setting of severe hypertension, remains a critical renal emergency leading to end-stage renal disease despite aggressive anti-hypertensive treatment. Recently, activation of the complement alternative pathway (AP) has been reported to play a prominent role in the pathogenesis of malignant nephrosclerosis. However, subsequent study failed to recapitulate the findings of genetic complement abnormalities in the disease. This study aimed to determine the presence of AP activation and genetic complement defects and establish their correlations to renal microangiopathy lesions, clinical features and prognosis in patients with malignant nephrosclerosis. METHODS Fifty patients with malignant hypertension and concomitant thrombotic microangiopathy (TMA) proven by renal biopsy were investigated; 25 cases of kidney donors who received zero-hour allograft biopsies were used as normal controls. Various renal TMA lesions in patients with malignant nephrosclerosis were reviewed and evaluated using a semi-quantitative scoring system. Deposition of C5b-9, C3a, C5a, C4d and mannose-binding lectin was assessed by immunohistochemistry. Co-localization of C5b-9 and CD34 was detected by confocal microscopy. Complement factor B (FB), factor P (FP; properdin), factor D (FD), factor H (FH), C3a and C5a levels were quantified by enzyme-linked immonosorbent assay in plasma and urine samples of patients with malignant nephrosclerosis and controls. Genetic abnormalities of complement components were analysed by whole-exome sequencing. RESULTS Renal biopsies of malignant nephrosclerosis showed identical histopathological and ultrastructural features to atypical haemolytic uraemic syndrome. C5b-9, C3a and C5a deposits were found along the walls of arteries/arterioles and glomerular capillaries and localized in the endothelial cells. Elevated plasma and urinary levels of FB, FP, FD, C3a and C5a as well as decreased FH levels were observed in patients with malignant nephrosclerosis compared with normal controls. The urinary levels of complement AP components, but not the plasma levels, were correlated with renal functions, prognosis and active TMA lesions except for arteriolar thrombi. Finally, mutations of the MCP, CFB, CFH and CFHR5 genes were identified in 8 of 20 patients with malignant nephrosclerosis. CONCLUSIONS Aberrant complement AP dysregulation was demonstrated and associated with the activity, severity and renal outcomes of malignant nephrosclerosis. This observation warrants screening for complement defects in patients with malignant nephrosclerosis for the potential use of complement regulators and also highlights the need for further investigation of the precise role of AP in the pathogenesis of the disease.
A laboratory study of the effect of time and temperature on the decline in Olsen P following phosphate addition to calcareous soils

Abstract. The effects of time and temperature on the changes in Olsen P after phosphate application were studied in 13 calcareous soils from Pakistan, an Oxisol from Colombia and an Inceptisol from England. The phosphate sorption reactions were monitored in two stages. The short‐term reaction (30 min shaking with added phosphate in the presence of the Olsen bicarbonate solution) showed that over this time the nature of the sorbing material and number of available sites for P adsorption were important but temperature was not. The extent of the short‐term sorption was not related to the amount of calcium carbonate. In the long‐term reaction (incubating the soils with phosphate at 10, 25 and 45 °C for one year) the amount of Olsen P decreased with time following a power relationship. Increased temperature increased the rate of reaction, following the Arrhenius principle i.e. Q10⊃ 3 (activation energy 83 kJ mol–1). The effects of time and temperature were well described by a modified power equation Y=a (1 +fTt)‐b, where Y is the amount of Olsen P extracted after time t, a is the Olsen P value after the short‐term reaction (the initial value), fT is the ratio of the rate constants at any two temperatures and b is a coefficient which represents the loss in extractability with time. On the basis of the initial Olsen P values and subsequent Olsen P values at different times and temperatures a unified decay curve Y/a= (1 +t)–0.20 was developed where the initial Olsen P values are normalized to 1. The parameters of this equation allow, with limitations, the prediction of changes in Olsen P in these soils if the initial Olsen P value of the soil is known.
SLC6A8 Knockdown Suppresses the Invasion and Migration of Human Hepatocellular Carcinoma Huh-7 and Hep3B Cells

Liver cancer is considered the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide. Currently, there is no specific and effective therapy for hepatocellular carcinoma. Therefore, developing novel diagnostic and therapeutic strategies against hepatocellular carcinoma is of paramount importance. Solute carrier family 6 member 8 (SLC6A8) encodes the solute carrier family 6-8 to transport creatine into cells in a Na+ and Cl-- dependent manner. SLC6A8 deficiency is characterized by intellectual disabilities, loss of speech, and behavioral abnormalities. Of concern, the association of SLC6A8 with hepatocellular carcinoma remains elusive. In this study, we revealed that SLC6A8 knockdown significantly induced apoptosis and suppressed the migration and invasion of Hep3B and Huh-7 cells. These findings depicted the vital role of SLC6A8 in the initiation and progression of human hepatocellular carcinoma.
Myricetin Apoptotic Effects on T47D Breast Cancer Cells is a P53-Independent Approach

Objective: Using nutraceuticals in cancer therapy is a strategy contributing with other approaches to promote apoptosis in cancer cells. Myricetin is a polyphenol flavonoid that forms main ingredients of various type of foods and beverages. The inducing properties of myricetin in apoptosis is reported by several investigations. The present study aimed to assess apoptotic effects of myricetin on T47D breast cancer cells and to evaluate part of the mechanisms of action. Materials and Methods: T47D breast cancer cells were assigned into five groups: control (cells in normal condition), myricetin (cells treated with myricetin IC50 concentration) in two different incubation times (24, 48 and 72 hours). MTT assay, annexin v assay, flow cytometry, caspase-3 assay and Real-time PCR were used to evaluate apoptosis in breast cancer cells. Results: The expression rate of apoptotic genes caspase-3, caspase-8, caspase-9, the ratio of BAX /Bcl-2 as well as the expression of P53, BRCA1, GADD45 genes were increased significantly after treatment of T47D breast cancer cells with myricetin. Annexin v assay confirmed significant expression of annexin as were displyed by flow cytometry. Conclusion: Myricetin enhances apoptosis in T47D breast cancer cells by evoking both extrinsic and intrinsic apoptotic pathways. myricetin may practices its apoptotic properties on T47D cells through inducing BRCA1- GADD45 pathway.