Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon-λ3 Exacerbates the Inflammatory Response to Microbial Ligands: Implications for SARS-CoV-2 Pathogenesis

Introduction Interferon lambdas (IFN-λs) are antiviral cytokines that restrict pathogen infection and dissemination at barrier surfaces. Controlled expression of IFN-λs efficiently eliminates acute infections by activating a suite of interferon stimulated genes that inhibit viral propagation and activate local immune cells. Excessive or prolonged production of IFN-λs can however mediate tissue inflammation and disrupt epithelial barriers in both viral and non-viral disease. The mechanism by which IFN-λs drive this disease pathogenesis is poorly understood but may be caused by IFN-λ-mediated amplification of other innate immune signaling pathways. Methods Monocyte-derived macrophages were differentiated ± IFN-λ3 and treated with KDO-lipid A, poly I:C or zymosan, representing bacterial, viral or fungal ligands, respectively. Transcriptome and protein expression were quantified by RNA sequencing/PCR and ELISA/bead array, respectively. Bioinformatic analysis was used to define transcription factor profiles and signaling pathways amplified by IFN-λ3. Finally, the SARS-CoV-2 dataset GSE152075 was queried to compare the effects of IFNL versus IFNA expression in relation to viral load and nasopharyngeal transcriptomes. Results IFN-λ3 exacerbated inflammatory and chemotactic responses unique to each microbial ligand, as measured by RNA sequencing and by ELISA/bead array. Functional annotation identified pathways amplified by IFN-λ3, including inflammasome activation. Inflammasome amplification was confirmed in vitro, as measured by caspase 1 activity and IL-1β cleavage. Lastly, SARS-CoV-2 infected nasopharyngeal transcriptomes expressing IFN-λs but not IFN-αs were implicated in myeloid cell-driven pathogenesis including neutrophil degranulation, complement and coagulation cascades. Discussion These data suggest that IFN-λs contribute to disease pathology by exacerbating innate immune responses during chronic or severe disease states. IFN-λs may contribute to SARS-CoV-2 disease severity, however further study is required to confirm true causation.
Association Between Olfactory Function and Asthma in Adults

Purpose Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are common asthma-associated upper airway diseases. Olfactory dysfunction, a common symptom among these patients, is an increasingly recognized condition that is associated with a reduced quality of life and major health outcomes. However, there are few studies on the association between olfactory function and asthma. We investigated the relationship between asthma and olfactory function. Patients and Methods A total of 146 patients with asthma aged >18 years were retrospectively analyzed from August 2019 to February 2020. Olfactory function was assessed using the Sniffin’ stick test or the YSK olfactory function test. We compared the clinical parameters of patients with olfactory dysfunction and patients with normosmia. Results Of the total participants, 68 (46.6%) showed olfactory dysfunction (hyposmia, n=31; anosmia, n=37). The patients with olfactory dysfunction were older, had longer durations of asthma, and a higher proportion of those with poor general health, CRS, and nasal polyps compared to patients with normosmia. However, there were no significant differences in the socioeconomic status, lung function, asthma severity, and use of inhaled corticosteroids or intranasal steroids between the two groups. Age (odds ratio: 1.044, 95% confidence interval: 1.009–1.081, P=0.012), poor general health (3.304, 1.231–8.863, P=0.018), CRS (2.589, 1.155–5.804, P=0.021), and nasal polyps (3.306, 1.1–9.94, P=0.033) were significantly associated with olfactory dysfunction. Conclusion Olfactory dysfunction was quite frequently observed in adults with asthma. Age, poor general health, CRS, and nasal polyps were significantly associated with olfactory dysfunction.
Infant Oral Healthcare and Anticipatory Guidance Practices among Dentists in a Pediatric Care Shortage Area

Objectives To assess dentists' practices and barriers towards infant oral healthcare (IOH) and anticipatory guidance (AG) in eastern Saudi Arabia. Methods A regional, cross-sectional survey was distributed to 340 (323 general dentists (GPs) and 17 pediatric dentists (PDs)) working in a governmental setting in eastern Saudi Arabia. A 23 close-ended, pilot-tested questionnaire was developed. The questionnaire asked about dentists' IOH and AG practices. A five-point Likert scale question assessed barriers interfering with AG practices. Descriptive and multivariate logistic regressions were used. Results Participation rate was 98.5% (335/340). Only 18% of GPs indicated performing IOH exams, while 100% of PDs do. About 90% of GPs would see children on a first visit when they are ≥3 years old, whereas 60% of PDs reported seeing one-year-old children. Older practitioners and those performing AG were more likely to perform IOH (OR = 1.8, CI = 1.06–3.1, and OR = 3.84, CI = 1.93–7.65, resp.). The majority of respondents (94%) felt their training did not prepare them to practice AG. “Parents bringing their children for the first time for emergency or existing conditions” was cited by 99% of respondents as a barrier to performing AG. Conclusion Increasing the awareness of GPs and parents about the importance of IOH and AG is crucial in improving children's oral health. Collaboration with pediatricians for early referral of children is equally important in increasing the awareness on prevention principles.
Non-responsive celiac disease in children on a gluten free diet

BACKGROUND Non-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population. AIM To determine the incidence, clinical characteristics and underlying causes of NRCD in children. METHODS Retrospective cohort study performed at Boston Children’s Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy. RESULTS Six hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up. CONCLUSION NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
Involvement of Tunisian General Practitioners in the Management of Patients at Risk of Infective Endocarditis: A Cross-Sectional Study

Objectives This work aimed to estimate the knowledge and practice of general dentists in the governorate of Manouba regarding the management of patients at risk of infective endocarditis. Materials and Methods A survey involving private sector general dentists in the governorate of Manouba was performed. It contained 21 questions, and it was addressed to 111 dentists. Only 82 dentists responded. To carry out the descriptive study, we used the SPSS software version 21.0. Results Our results proved the lack of knowledge among dentists in the governorate of Manouba with regard to the management of patients at risk of infective endocarditis. An overestimation of the risk and an overprescription of antibiotic were found in order to ensure an over-protection for the patients as well as the dentist. In fact, 85.4% of these dentists prescribed antibiotic prophylaxis for the two groups of patients (high risk and moderate risk). Only 9.8% followed the right modality of antibiotic prophylaxis prescription; 4.9% of the dentists prescribed antibiotic only 1 hour before the act and 4.9% of them prescribed antibiotic 1 hour before the act and continued the treatment in case of the presence of an infectious site. Conclusion A discrepancy towards an over-estimation of risk and overprescription of antibiotic was found between the recommendations and real practice. Similar studies in the other governorates of Tunisia are recommended in order to better understand the problem.
Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as neutrophil × monocyte/lymphocyte count (109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC (P < 0.040). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC (P < 0.015). In addition, in small-duct type ICC, NLR and LMR were correlated with OS (P < 0.025), whilst CEA and CA242 were correlated with DFS (P ≤ 0.010). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.
Calculation of risk-based detection limits for radionuclides in the liquid effluents from Korean nuclear power plants

ABSTRACT In order to review if present detection limits of radionuclides in liquid effluent from nuclear power plants are effective enough to warrant compliance with regulatory discharge limits, a risk-based approach is developed to derive a new detection limit for each radionuclide based on radiological criteria. Equations and adjustment factors are also proposed to discriminate the validity of the detection limits for multiple radionuclides in the liquid effluent with or without consideration of the nuclide composition. From case studies to three nuclear power plants in Korea with actual operation data from 2006 to 2015, the present detection limits have turned out to be effective for Hanul Unit 1 but may not be sensitive enough for Kori Unit 1 (8 out of 14 radionuclides) and Wolsong Unit 1 (9 out of 42 radionuclides). However, it is shown that the present detection limits for the latter two nuclear power plants can be justified, if credit is given to the radionuclide composition. Otherwise, consideration should be given to adjustment of the present detection limits. The risk-based approach of this study can be used to determine the validity of established detection limits of a specific nuclear power plant.
Bank risk and lending supply during conventional and unconventional monetary policies

This paper examines the effect of bank risk on the transmission mechanism of monetary policy for a sample of 149 US banks over the period from 2007 to 2016. Using quarterly balance sheet data and employing a GMM approach to deal with endogeneity concerns, we document that bank risk positions are relevant for the transmission mechanism through the bank lending channel during the FED Quantitative easing (QE) programmes. We conclude that QE programs helped banks to supply new loans through the reduction of bank risk conditions, as perceived by financial market investors. These results are relevant for the way monetary policy was conducted in response to the financial crisis, since QE programmes were effective in reducing the heterogeneous transmission of the monetary policy in the US.
Making sense of non-randomized comparative treatment studies in times of Covid-19: A case study of tocilizumab

BACKGROUND Tocilizumab (TCZ) is an interleukin-6 inhibitor and the second established effective drug for the treatment of hospitalized patients with Covid-19. In this study, we sought to validate the recent positive findings from the randomised clinical trial RECOVERY and to evaluate the challenges in the analysis and interpretation of non-randomized comparative effectiveness studies in Covid-19. METHODS We performed a retrospective cohort study using an openly available database of hospitalised Covid-19 patients in Spain. The primary outcome was all-cause in-hospital mortality at 28 days. We used multivariable Fine and Gray competing risk models which adjusted for both fixed and time-variant confounders to investigate the effect of TCZ on the primary outcome. RESULTS We analysed 2547 patients hospitalised with Covid-19 between 1st January and 28th June 2020. Patients in the TCZ group tended to have more severe Covid-19 at admission, as measured by biomarkers of disease severity including CRP, D-dimer and LDH. At 28 days, 91 out of 440 TCZ patients had died compared to 267 out of 2107 patients in the control group. In multivariable analysis, there was no evidence of an association between TCZ and the primary outcome (adjusted hazard ratio 1.20, 95% CI 0.86 to 1.64, P=0.26). CONCLUSIONS Our observational study failed to find a benefit of TCZ on all-cause in-hospital mortality in Covid-19 patients compared with randomized trials, highlighting the impact that unmeasured confounding and other sources of bias can have in a retrospective observational setting. For future observational studies, we recommend prospective data collection to ensure all variables have the necessary quality, completeness and timing for reliable treatment evaluation.
ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration

Stem cell approaches have become an attractive therapeutic option for intervertebral disc degeneration (IVDD). Nucleus pulposus mesenchymal stem cells (NP-MSCs) participate in the regeneration and homeostasis of the intervertebral disc (IVD), but the molecular mechanisms governing these processes remain to be elucidated. Acid-sensing ion channels (ASICs) which act as key receptors for extracellular protons in central and peripheral neurons, have been implicated in IVDD where degeneration is associated with reduced microenvironmental pH. Here we show that ASIC1 and ASIC3, but not ASIC2 and ASIC4 are upregulated in human IVDs according to the degree of clinical degeneration. Subjecting IVD-derived NP-MSCs to pH 6.6 culture conditions to mimic pathological IVD changes resulted in decreased cell proliferation that was associated with cell cycle arrest and induction of senescence. Key molecular changes observed were increased expression of p53, p21, p27, p16 and Rb1. Instructively, premature senescence in NP-MSCs could be largely alleviated using ASIC inhibitors, suggesting both ASIC1 and ASIC3 act decisively upstream to activate senescence programming pathways including p53-p21/p27 and p16-Rb1 signaling. These results highlight the potential of ASIC inhibitors as a therapeutic approach for IVDD and broadly define an in vitro system that can be used to evaluate other IVDD therapies.
A new diphenyl ether from Parmotrema indicum Hale growing in Vietnam

Abstract Chemical investigation of the lichen Parmotrema indicum Hale led to the isolation of one new diphenyl ether, parmetherine D (1), along with eight known compounds (2-9). The structures were determined by analysis of MS and NMR data and by comparison with the literature. Compounds 1, 2, and 7 were evaluated for α-glucosidase inhibition. Only compound 1 exhibited significant inhibition.
Real-world assessment of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nasopharyngeal swab testing in a region with a high burden of coronavirus disease 2019 (COVID-19)

Abstract Concerns persist regarding possible false-negative results that may compromise COVID-19 containment. Although obtaining a true false-negative rate is infeasible, using real-life observations, the data suggest a possible false-negative rate of ˜2.3%. Use of a sensitive, amplified RNA platform should reassure healthcare systems.
MOVEMENT ASSESSMENT BATTERY FOR CHILDREN-SECOND EDITION: THEORETICAL ADEQUACY OF A MOTOR ASSESSMENT INSTRUMENT

ABSTRACT Objective: To investigate the adequacy of the theoretical model of the Movement Assessment Battery for Children-Second Edition (MABC-2) instrument. Methods: 582 children, of both sexes, aged between 3 and 5 years and residents in the city of Maringá (state of Paraná, Southern Brazil) participated in the study. Data were collected from May/2014 to June/2015 and analyzed using descriptive and inferential statistics. Results: The evidence obtained from exploratory factor analysis indicated the presence of two factors, which was the option that best fitted the explanatory model. Hence, it was necessary to regroup the motor tasks of the dimensions “Aiming & catching” and “Balance” into only one dimension. It is noteworthy that the “Bicycle trail” motor task did not fit the model, as it presented a low and negative factor load in the analyzed dimensions. In the confirmatory factor analysis, adequate adjustment indices were observed for the tested model, which confirmed the non-classification of the “Bicycle trail” motor task in the original dimension. Conclusions: After removing the “Bicycle trail” motor task, the adjusted two-factor model seems to be the most appropriate to assess the motor performance of children participating in the study.
Identification and expression profiling of genes involved in circadian clock regulation in red dragon fruit (Hylocereus polyrhizus) by full-length transcriptome sequencing

ABSTRACT Crassulacean acid metabolism (CAM) plants fix CO2 at night, exhibiting a reversed regulatory pattern of metabolomic pathways compared with most model plants, which have C3 and C4 pathways. In this study, we used a valuable tropic fruit, red dragon fruit (Hylocereus polyrhizus), as model plant to identify and analyze the circadian regulation genes. Due to the absence of red dragon fruit’s whole-genome dataset, we established a full-length transcriptome dataset using single-molecule real-time (SMRT) sequencing method. A 7.66-Gb dataset with 4,552,474 subreads was generated, with an average length of 1,683 bp and an N50 of 2,446 bp. Using this dataset, we identified center oscillator genes: CCA1 (CIRCADIAN CLOCK ASSOCIATED1), ELF3 (EARLY FLOWERING 3), GI (GIGANTEA), LHY (LATE ELONGATED HYPOCOTYL), LNK1 (NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED 1), and TOC1 (TIMING OF CAB EXPRESSION 1); a gene for the input pathway: CRY1 (CRYPTOCHROME); a gene for the output pathway: CO (CONSTANS); and genes related to the CAM pathway: MDH (MALATE DEHYDROGENASE), ME (MALIC ENZYMES), and PPDK (PYRUVATE PHOSPHATE DIKINASE). We further established the 24-h rhythmic expression pattern of these genes and classified these into three groups: HpCCA1, HpELF3, HpLHY, HpLNK1, and HpGI have expression peaks during the day; HpTOC1, HpCO, and HpCRY1 have highest expression levels at night; The genes involved in the CAM pathways, namely, HpMDH, HpME1, and HpPPDK, have double expression peaks in the day and night. Comparison of these expression patterns between red dragon fruit and model plants could provide clues in understanding the circadian clock regulation and the activity of the CAM pathways in cactus plants.
Flavonoid-rich fraction of Lasianthera africana leaves alleviates hepatotoxicity induced by carbon tetrachloride in Wistar rats

Abstract Lasianthera africana P. Beauv. (Icacinaceae) is a good source of natural antioxidants, having the potential to protect against oxidative stress-related diseases and complications. This study investigated the antioxidant, hepatoprotective and curative effects of flavonoid-rich fraction of L. africana leaves (LAFRF) against carbon tetrachloride-induced hepatotoxicity in Wistar rats. Phytochemical, nutrient content, and in vitro antioxidant activity of LAFRF were determined by standard methods. Fifty Wistar rats were randomized into 10 groups (n = 5). Groups 1 and 2 served as normal and CCl4 controls, respectively. Groups 3A–6A constituted the protective study while groups 3B–6B represented the curative study. The effects of LAFRF at 3, 10, and 30 mg/kg body weight (b.w.) on lipid peroxidation, antioxidant status, liver enzymes activities, and histology of CCl4-intoxicated rats were assessed. LAFRF total flavonoids (281.05 ± 7.44 mg QE/g), indicated LD50 above 5000 mg/kg b.w. , and scavenged ABTS*+ with an IC50 of 5.05 ± 0.00 µg/mL relative to butylated hydroxytoluene (4.16 ± 0.00 µg/mL), and a concentration-dependent increase in total antioxidant capacity. Carbon tetrachloride (1 mL/kg) triggered significant (p < 0.05) increases in malonedialdehyde concentration (2.67 ± 0.21 mg/mL), with a corresponding decline in antioxidant status, and increases in alkaline phosphatase, alanine and aspartate aminotransferase activities (68.00 ± 9.59 IU/L, 79.60 ± 5.03 IU/L and 81.80 ± 3.96 IU/L), respectively. LAFRF significantly (p < 0.05) lowered lipid peroxidation levels, liver enzyme activities, increased antioxidant status, and improved hepatic histo-architecture of pre- and post LAFRF-treated rats. This demonstrates its high antioxidative, hepatoprotective and curative effects, indicating its potential for future drug development.