bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged nucleic acid conversion and false-negative RT-PCR results in Indonesian patients with COVID-19: A case series
Authors: Trisnawati Ika , Khair Riat Al , Fauzi Aditya Rifqi , Gunadi
Published: July 2020

Background: Prolonged nucleic acid conversion and false-negative results of real-time reverse transcription polymerase chain reaction (RT-PCR) might occur in some patients with COVID-19 rather than recurrence of infection. Here, we reported four cases of COVID-19 with prolonged nucleic acid conversion and false-negative results of RT-PCR in our institution.Case presentation: Case 1: A 36-year-old-male patient complained of coughing up phlegm one week before admission. His chest X-rays showed mild pneumonia in the right lung. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR twice (the 6th and 8th tests) from a total of 11 swab tests. Case 2: A 54-year-old-male patient complained of shortness of breath that worsened with activity. He had a comorbidity of diabetes. His chest X-rays showed inhomogeneous opacity on bilateral paracardial and lateral aspects. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR once (the 5th test) from a total of 8 swab tests. Case 3: A 47-year-old man presented with complaints of fever, cough, sore throat, and diarrhea. He had comorbidities of asthma and heart rhythm disorders. His chest X-rays showed bilateral pneumonia. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also showed negative results of RT-PCR twice (the 4th and 6th tests) from a total of 11 swab tests. Case 4: A 56-year-old-female complained of lethargy and diarrhea. She has a history of hyperthyroidism. His chest X-rays showed bilateral pneumonia. She was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, she also had negative results of RT-PCR twice (the 2nd and 10th tests) from a total of 14 swab tests.Conclusions: Our cases further confirmed the occurrence of prolonged nucleic acid conversion and the possibility of false negative results of RT-PCR in patients with COVID-19 instead of recurrence of infection. These findings might have an implication on the management of patients with COVID-19 who have already clinically and radiologically recovered, particularly related to subsequent spreading of the infection in the community.
Reversible Dual Anionic-Redox Chemistry in NaCrSSe with Fast Charging Capability
Authors: Shi Ding-Ren , Shadike Zulipiya , Wang Tian , Yang Si-Yu , Xia He-Yi , Yue Ji-Li , Hu Enyuan , Bak Seong-Min , Yue Xin-Yang , Zhou Yongning , Ma Lu , Ghose Sanjit , Wu Tianpin , Zhang Qinghua , Xing Zhe , Zhang Yan-Ning , Zheng Lei , Gu Lin , Yang Xiao-Qing , Fu Zhengwen
Published: July 2020

Utilizing the anionic redox reaction opens new approaches for the development of new battery cathode materials with extra capacities. Although, it suffers from several obstacles such as voltage hysteresis and sluggish kinetics. In this paper, a new layered chalcogenide-based on dual anionic-redox reaction is reported. The newly designed layered NaCrSSe exhibits the capacity of almost all Na+ intercalation/deintercalation (137 mAh g-1 at 50 mA g-1), and a unique charge/discharge feature with a small polarization of 0.15 V and high energy efficiencies of ~92% in initial cycles. Furthermore, a superior high-rate charge capacity of 115.5mAh g-1 (83.7% retention) was achieved at 27.8 C (4000 mA g-1), which is impressive in all bulk materials for sodium-ion batteries. Systematic characterization studies on structure evolution and DFT calculation show the charge compensation of S and Se anions during cycling. These results will enrich the anion redox chemistry and provide valuable information for developing new anion redox based cathode materials with high capacity and fast kinetics.
Structure of human steroid 5α-reductase 2 with anti-androgen drug finasteride
Authors: Xiao Qingpin , Wang Lei , Supekar Shreyas , Shen Tao , Liu Heng , Ye Fei , Huang Junzhou , Fan Hao , Wei Zhiyi , Zhang Cheng
Published: July 2020

Human steroid 5α-reductase 2 (SRD5α2) as a critical integral membrane enzyme in steroid metabolism catalyzes testosterone to dihydrotestosterone. Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride as SRD5α2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia, which have recently been indicated in the treatment of COVID-19. The molecular mechanisms underlying enzyme catalysis and inhibition remained elusive for SRD5α2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information. Here, we report a crystal structure of human SRD5α2 at 2.8 Å revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the membrane. Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region regulating the NADPH/NADP+ exchange. Mapping disease-causing mutations of SRD5α2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and will facilitate drug development.
Social predictors of alcohol use and cessation during pregnancy among Japanese women: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study
Authors: Murakami Keiko , Obara Taku , Ishikuro Mami , Ueno Fumihiko , Noda Aoi , Kuriyama Shinichi
Published: July 2020

Background: Most studies on social predictors of alcohol use have been conducted at one time point during pregnancy or using postpartum retrospective reports. Furthermore, the studies were mainly conducted in Western countries. We aimed to prospectively examine social predictors of alcohol use and cessation during pregnancy in Japan.Methods: This prospective study was part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. Pregnant women were recruited at approximately 50 obstetric clinics and hospitals in Miyagi Prefecture in Japan. We analyzed 11592 pregnant women who completed the questionnaires administered in early pregnancy and middle pregnancy. Women were dichotomized as current drinkers or non-drinkers in both early and middle pregnancy. Age, education, income, work status, and psychological distress were used as social predictors. Multivariate logistic regression analyses were conducted to examine associations between these predictors and alcohol use in early and middle pregnancy. Associations with alcohol cessation between early pregnancy and middle pregnancy were also examined.Results: Prevalence of alcohol use in early and middle pregnancy was 20.9% and 6.4%, respectively. Higher education was associated with alcohol use in early pregnancy and alcohol cessation during pregnancy; the odds ratios (ORs) of ≥university education compared with ≤high school education were 1.47 (95% confidence interval [CI], 1.30–1.66) and 1.31 (95% CI, 1.00–1.71), respectively. Work status was associated with alcohol use in both periods and alcohol cessation during pregnancy; for alcohol cessation, the OR of working in early pregnancy only compared with not working in both periods was 1.72 (95% CI, 1.03–2.88).Conclusions: Women with higher education were more likely to consume alcohol in early pregnancy and to cease between early pregnancy and middle pregnancy. Working women were more likely to consume alcohol throughout pregnancy in Japan.
Biochemical and Biophysical characterization of the main protease, 3-chymotrypsin-like protease (3CLpro), from the novel coronavirus disease 19 (COVID-19)
Authors: Ferreira Juliana C. , Rabeh Wael M.
Published: July 2020

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here will improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the drug discovery and antiviral design for therapeutics against COVID-19.
Simultaneous detection and ribotyping of Clostridioides difficile, and toxin gene detection directly on fecal samples
Authors: Rossen Tessel Meike van , Prehn Joffrey van , Koek Alex G. , Jonges Marcel , Houdt Robin van , Mansfeld Rosa van , Kuijper Ed J. , Vandenbroucke-Grauls Christina M.J.E. , Budding Andries E.
Published: July 2020

Background: Clostridioides difficile is the most common cause of nosocomial diarrhea. Ribotyping of cultured strains by a PCR-based test is used to study potential transmission between patients. We aimed to develop a rapid test that can be applied directly on fecal samples for simultaneous detection and ribotyping of C. difficile, as well as detection of toxin genes. Methods: We developed a highly specific and sensitive primer set for simultaneous detection and ribotyping of C. difficile directly on total fecal DNA. Toxin genes were detected with primers adapted from Persson et al. (CMI, 2008). Our study set comprised 130 fecal samples: 65 samples with positive qPCR for C. difficile toxin A/B genes and 65 C. difficile qPCR negative samples. PCR products were analyzed by capillary gel electrophoresis. Results: Ribosomal DNA fragment peak profiles and toxin genes were detected in all 65 C. difficile positive fecal samples and in none of the 65 C. difficile negative samples. The 65 samples were assigned to 27 ribotypes by the Dutch reference laboratory. Our peak profiles corresponded to these ribotypes, except for two samples. During a C. difficile outbreak, patients were correctly allocated to the outbreak-cluster based on the results of direct fecal ribotyping, before C. difficile isolates were cultured and conventionally typed. Conclusion: C. difficile ribotyping directly on fecal DNA is feasible, with sensitivity and specificity comparable to that of diagnostic toxin gene qPCR and with ribotype assignment similar to that obtained by conventional typing on DNA from cultured isolates. This supports simultaneous diagnosis and typing to recognize an outbreak.
A nomogram based on pretreatment CT radiomics features for predicting complete response to chemoradiotherapy in patients with esophageal squamous cell cancer
Authors: Luo Hesan , Huang Shao-Fu , Xu Hong-Yao , Li Xu-Yuan , Wu Sheng-Xi , Wu De-Hua
Published: July 2020

Purpose
To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features.
Methods
Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions.
Results
A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUCs of Rad-score was 0.812 (95%CI: 0.742–0.869) in the training set and 0.744 (95%CI: 0.632–0.851) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with P values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95%CI: 0.779–0.897) in the training set and 0.807 (95༅CI: 0.691–0.894) in the validation set༎Delong test showed that the nomogram model was significantly superior to the clinical staging, with P < 0.001 in the training set and P = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%.
Conclusion
We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.
Automated, Cassette-Based Isolation and Formulation of High-Purity [61Cu]CuCl2 from Solid Ni Targets
Authors: Pettersson Johan , Kutyreff Christopher J , Engle Jonathan W , Gagnon Katherine
Published: July 2020

Background: A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics and generally lengthy separation chemistries for 64Cu/ 64Ni, upon which 61Cu chemistry is often based.Methods: A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [ 61Cu]CuCl2 , removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions.Results: 61Cu saturation yields of 190 ± 33 MBq/µA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl 2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10-5 % vs. 61Cu by activity, Ni separation factors ≥(2.2 ± 1.8) × 106 , EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively.Conclusion: High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.﻿
Imiquimod does not elicit inflammatory responses in the skin of the naked mole rat (Heterocephalus glaber)
Authors: Kisipan Mosiany Letura , Ojoo Rodi Omondi , Kanui Titus I. , Abelson Klas S.P.
Published: July 2020

Objective Naked mole rat (Heterocephalus glaber) has recently attracted interest in biomedical research due to its exceptional longevity, cancer resistance and tolerance to potentially harmful conditions or stimuli. Given its unique attributes, this study was designed to characterize inflammatory skin reactions of this animal to topical application of imiquimod, a toll-like receptor 7 and 8 agonist that triggers psoriasis-like skin reaction. Results Imiquimod did not cause the expected psoriasis-like skin changes. There was no epidermal thickening and a straight epidermo-dermal boundary was maintained. There was no parakeratosis and the granular layer of epidermis was well formed. In the dermis, there was no leukocyte infiltration. This points to an exceptional nature of inflammatory/immune responses of this animal, but the mechanism could not be explained by our results. Naked mole rat could be a valuable negative model for studying psoriasis and other inflammatory skin conditions but as a prerequisite, there is need for further investigations to establish the mechanisms behind its lack of response to imiquimod.
Anti-piroplasmic Activity of Novobiocin as Heat Shock Protein 90 Inhibitor Against in-vitro Cultured Theileria Equi and Babesia Caballi Parasites
Authors: Suthar Abhinav , Maji Chinmoy , Gopalakrishnan A. , Raval S. H. , Kumar Rajender , Kumar Sanjay
Published: July 2020

Background: Theileria equi and Babesia caballi are the causative agents for equine piroplasmosis (EP). Currently, imidocarb dipropionate (ID) is the only available drug for treating clinical form of EP. Serious side effects and uncompleted clearance of infection is major drawback of ID. Heat-shock proteins (HSP) play a vital role in the life cycle of these haemoprtozoa by way of preventing alteration in protein conformation. These HSPs are activated during transfer of EP sporozoites from tick vector (poikilotherm) to natural host (homeotherm) and helped it for survival. In this present study we have targeted the heat shock protein 90 pathway of T. equi and B. caballi by its inhibitor drug - novobiocin. Methods: Dose-dependent efficacy of novobiocin drug was observed on growth of T. equi and B. caballi in in-vitro culture. Cell cytotoxicity on host peripheral mononuclear cells (PBMCs) was also checked with different concentration of novobiocin. It was also checked for its haemolytic activity on equine erythrocyte (RBCs) by standard technique. In-vivo organ toxicity of novobiocin was also assessed in mice model with identified methods. Results: IC50 (50 % Inhibitory concentration) value of novobiocin against T. equi and B. caballi was 165 µM and 84.85 µM, respectively. Novobiocin significantly arrested the in-vitro growth of T. equi and B. caballi parasites at respective 100 μM and 200 μM drug concentration. In-vitro treated parasites become dead with distorted nuclear material and showed no further viability. The drug was found safe on the equine PBMCs and RBCs cell line even at 1000 µM concentration and CC50 (50 %, cytotoxicity concentration) values were 11.628 mM and 261.97 mM. A very high specific selective index (SSI) was also observed 70.47 and 1587 for respective equine PBMCs and RBCs. Organ specific biochemical markers and histopathological examination indicated no adverse effect of the drug at a dose rate of 50 mg/kg of body weight in mice model.Conclusions: The results clearly indicating the growth inhibitory efficacy of novobiocin against T. equi and B. caballi parasites and its safety on host cell lines with very high SI. Hence, it can be inferred that Theileria/Babesia Hsp-90 family are the potential drug targets worthy of further investigation.
Interleukin-25-Mediated Resistance Against Intestinal Trematodes Does Not Depend on The Generation of Th2 Responses
Authors: Álvarez-Izquierdo Maria , Pérez-Crespo Miguel , Esteban J. Guillermo , Muñoz-Antoli Carla , Toledo Rafael
Published: July 2020

Background: Interleukin-25 (IL-25) is recognized as the most relevant initiator of protective Th2 responses in intestinal helminth infections. It is well known that IL-25 induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. Echinostoma caproni has been extensively used as an experimental model to study the factors determining the resistance to intestinal infections. Herein, we assessed the role of IL-25 in the generation of resistance in mice to E. caproni infections. Methods: To this purpose, we analyze the fatros that determine the production of IL-25 in mice experimentally infected with E. caproni and its consequences in the polarization of the immune response and the resistance to infection.Results: We have determined that the role of IL-25 in the polarization of the immune response differs between the primary and secondary response. IL-25 is required for the development of a Th2 phenotype in primary E. caproni infections but could also promote the differentiation to Th2 memory cell subsets that enhances type 2 responses in memory responses. However, development of Th2 responses does not induce resistance to infection. Th2 phenotype does not elicit resistance and IL-25 is responsible for the resistance regardless of the type 2 cytokine activity and STAT6 activation. Alternative activation of macrophages induced by IL-25 could be implicated in the resistance to infection. Conclusions: In contrast to primary infection, secondary infection elicits a type 2 response, even in the absence of IL-25 expression. Despite the development of a type 2 response, mice are susceptible to secondary infection in relation to the lack of IL-25. Resistance to infection is due to IL-25, which acts autonomously from Th2 response in the parasite clearance.
Intelligent Prediction of RBC Demand in Trauma Patients
Authors: Feng Yannan , Xu Zhenhua , Liu Junting , Sun Xiaolin , Wang Deqing , Yu Yang
Published: July 2020

Background: The vital signs of trauma patients are complex and changeable, and the prediction of blood transfusion demand mainly depends on doctors' experience and trauma scoring system, therefore it can’t be accurately predicted. In this study, the decision tree algorithm (Classification and Regression Tree, CRT and eXtreme Gradient Boosting, XGboost) of machine learning were proposed to the demand prediction of traumatic blood transfusion, hoping to provide technical support for doctors.Methods: Total 1371 trauma patients who were diverted to the emergency department from 2014.1 to 2018.1 were collected from the emergency trauma database. The vital signs, laboratory examination parameters and blood transfusion volume were used as variables, and the non-invasive parameters and all (non-invasive + invasive) parameters were used to construct the intelligent prediction model of RBC demand by logistic regression (LR), CRT and Xgboost. The prediction accuracy of the model was compared with the Area Under Curve (AUC). Results: The studies we have performed showed that non-invasive parameters were used to predict blood transfusion, LR method was the best, AUC 0.72 (95% confidence interval [CI] 0.657-0.775), highest than CRT AUC 0.69 (95%CI 0.633-0.751) and Xgboost AUC 0.71 (95%CI 0.654-0.756) (P<0.05). Trauma site and shock index are important prediction parameters. All the parameters to predict, Xgboost was the best with AUC 0.94 (95%CI 0.893-0.981), which was highest than LR AUC 0.80 (95%CI 0.744-0.850) and CRT AUC 0.82 (95%CI 0.779-0.853) (P<0.05). Hematocrit/Hemoglobin are important prediction parameters. Conclusions: The prediction model of red blood cell transfusion in trauma patients constructed by decision tree algorithm can be used as a technical support to assist doctors to make rapid and accurate blood transfusion decisions in emergency rescue environment, so as to improve the success rate of patient treatment.
Exploring Proximal LGBTQ+ Minority Stressors within Physical Activity Contexts From a Self-Determination Theory Perspective
Authors: Herrick Shannon , Rocchi Meredith A. , Sweet Shane N. , Duncan Lindsay R.
Published: July 2020

Background: LGBTQ+ individuals experience challenges such as discrimination and marginalization (referred to as minority stressors) that are detrimental to their mental and physical health. Specifically, proximal or internalized LGBTQ+ minority stressors may influence motivation for and willingness to participate in physical activity. Methods: The purpose of this study was to explore whether proximal LGBTQ+ minority stressors, as indicators of the social-environmental context, would relate to the basic psychological needs—motivation—physical activity pathway, as per self-determination theory. An online cross-sectional survey was completed by 778 LGBTQ+ adults. Results: Results from structural equation modelling analyses support that proximal LGBTQ+ minority stressors are associated with decreased reported need satisfaction (β = -.36) which, in turn, is associated with autonomous motivation (β = .53) and reported physical activity participation (β = .32). Conclusions: Future research focused on increasing LGBTQ+ participation in physical activity should investigate the effects of (a) reducing proximal LGBTQ+ minority stressors, and (b) better supporting LGBTQ+ adults’ autonomy, competence, and relatedness within physical activity contexts.
Correlation study between Interleukin-17 Gene Polymorphisms and risk of development of recurrent aphthous ulcer in Han Chinese Population
Authors: Xiang Haidong , Cheng Dongmei , Guo Han , Wang Yan , Jia Zhiyu , Gao Qi
Published: July 2020

Objective Interleukin-17 (IL-17) is a pleiotropic cytokine which plays important role in the inflammatory diseases.Methods: Polymorphisms of IL-17A rs2275913 and IL17F rs763780 were measured in 125 RAU cases and 116 healthy controls. The polymerase chain reaction-restriction fragment length was measured. The genotype distribution and disease risk, and its’ relationship with RAU severity was analyzed. Results: RAU risk were related with polymorphism of IL-17 gene at rs2275913 site after adjusting BMI, sex, age, smoking and drinking status (AA vs. GG: odds ratio (OR), 1.624; 95% confidence interval (CI), 1.125–2.250; P = 0.030; A allele vs. G allele: OR, 1.192; P = 0.037; 95% CI, 1.012–1.404;). In addition, the rs763780 variant genotypes (TC and CC) and C allele also have higher relevance to RAU compared with subjects who bears the TT genotype (TC vs. TT, OR: 1.312; P = 0.039; 95% CI: 1.017–1.692; CC vs. TT, OR: 2.812, P = 0.006, 95% CI: 1.338-5.909; C allele Vs. T allele, OR:1.413, P=0.002, 95% CI:1.141-1.751). We also found serum IL-17 levels were greatly higher in RAU patients compared with controls (P = 0.001), and serum IL17 concentration is correlated with IL17 polymorphism. Conclusion: Our research showed polymorphisms of IL-17 gene might related to the high-risk of RAU occurrence.
Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study
Authors: Choi Hyunok , Dostal Miroslav , Pastorkova Anna , Rossner Pavel , S Radim
Published: July 2020

Background
For nearly 50% of the asthmatic children, effective treatments against exacerbation do not exist, because existing therapies do not target the mechanistic origins of discrete sub-diseases (i.e. endotypes). While non-atopic and atopic asthma represent known phenotypes, it is unknown whether they arise from disparate processes. The objective is to classify two phenotypes (non-atopic vs. atopic asthma) into endotypes using polyaromatic hydrocarbon, namely, benzo[a]pyrene, as putative marker of endotype.
Methods
In a case-control study, lean controls (i.e. reference) are compared against three outcomes of interest – overweight/obese controls, lean asthmatics (without overweight/obesity), and overweight/obese asthmatics – in terms of benzo[a]pyrene exposure level, plasma 15-Ft2-isoprostane, urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine, as well as their history of co-morbidities until age three, following atopy- and gender-stratification.
Results
The non-atopic girls are associated with significantly elevated median benzo[a]pyrene for the lean asthmatics (11.2 ng/m3) and the overweight/obese asthmatics (18.0 ng/m3), compared to the non-atopic control girls (4.3 ng/m3; p-value < 0.001). A natural-log (ln) unit increase B[a]P exposure predicts 10-times greater odds of asthma in the lean non-atopic boys, while the same exposure is not associated with asthma among the lean atopic boys. The diagnosis of lung function deficit, which only appear among those with highest median value of B[a]P, appears to be a particularly important predictor of non-atopic asthma only. The non-atopic asthmatic boys with highest exposure to B[a]P (median, 20 ng/m3) were also positively diagnosis with lung function deficit, compared to the non-atopic controls (median, 4.3 ng/m3). An elevated exposure to B[a]P is associated with depressed systemic oxidant levels, and correspondingly elevated odds of non-atopic asthma. On the other hand, low ambient exposure to B[a]P, and weakly pro-inflammatory effect of oxidative stress of such exposure, is not associated with atopic asthma.
Conclusions
Ambient benzo[a]pyrene is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among the lean children. Our observation, once validated in a prospective cohort design, could aid the development of targeted and personalized therapies in children in whom the respiratory injuries are still reversible.
Genome-wide identification and function analysis of ERF2 gene family in response to disease resistance against Stemphylium lycopersici in tomato
Authors: Yang Huanhuan , Sun Yaoguang , Wang Hexuan , Jiang Jingbin , Li Jingfu
Published: July 2020

Background
APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERFs) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study is to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by Virus-induced Gene Silencing (VIGS) technique.
Results
In this experiment, 134 ERF genes were excavated and subjected to bioinformatic analysis. This experiment divided 134 ERF members into twelve groups based on the conserved domain of the genes. Specific expression of the tomato ERF transcription factor family genes in different organs. Combined with RNA-seq, we found that the expression of 18 ERF transcription factor increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the silenced ERF2 plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance.
Conclusions
In this study, we identified and analyzed the members of tomato ERF family by bioinformatics methods, and classified, described and analyzed these genes. we found that ERF2 was positively regulated tomato resistance to S. lycopersici by VIGS. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.
Correlates of Children’s Physical Activity During the Covid-19 Confinement in Portugal
Authors: Pombo André , Luz Carlos , Rodrigues Luis Paulo , Ferreira Carlos , Cordovil Rita
Published: July 2020

Objectives: Aiming to understand the role of household variables on the percentage of physical activity (%PA) during the COVID-19 confinement, an anonymous online survey was launched to be completed by Portuguese families with children. Study Design: A Cross-sectional study design using an anonymous online survey that was launched to assess how Portuguese families with children under 13 years of age adjusted their daily routines to this situation. Methods: Separate ANOVAs were performed to investigate how factors, such as the number of children, age, sex, the housing characteristics, and the adults’ job situation, can affect the percentage of time for physical activity (%PA). Results: Findings, based on data from 2159 children, indicate that: I) Boys and girls did not differ in the %PA on any of the age groups; II) Children with an outdoor space and who had other children in the household were significantly more active (p<.001); III) Children from families with all adults working from home showed lower levels of %PA; IV) Being younger, having a big outdoor space, having other children in the household, and having at least one adult free from working from home, were significant positive predictors of children’s %PA, explaining 21% of the overall variance. Conclusion: Time allocated for PA during this period is reduced compared to what is usually reported on normal days. It is necessary to find strategies to increase children's PA, especially in families where both parents are working and have no outdoor space.
Clinical utility of cycle threshold values in the context of COVID-19
Authors: Rao Sonia N. , Manissero Davide , Steele Victoria , Pareja Josep
Published: July 2020

BackgroundThe ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.ObjectivesWe aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.SourcesA PubMed search was conducted on 1st June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data was extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.ContentData from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity and an association was observed in 8 (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.ImplicationsData suggest that lower Ct values may be associated with worse outcomes, and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.
Adherence predictor variables in AIDS patients: An empirical study using the data mining-based RFM model
Authors: Li Min , Wang Qunwei , Shen Yinzhong
Published: July 2020

Background
Highly active antiretroviral therapy (ART) is still the only effective method to stop the disease progression in acquired immunodeficiency syndrome (AIDS) patients. However, poor adherence to the therapy makes it ineffective. In this work, we construct an adherence prediction model of AIDS patients using the classical recency, frequency and monetary value (RFM) model in the data mining-based customer relationship management model to obtain adherence predictor variables.
Methods
We cleaned 257305 diagnostic data elements of AIDS outpatients in Shanghai from August 2009 to December 2019 to obtain 16440 elements. We tested the RFM and RFm (R: recent consultation month, F: consultation frequency, M/m: total/average medical costs per visit) models, three clustering methods (K-means, Kohonen and two-step clustering) and four decision algorithms (C5.0, the classification and regression tree, Chi-square Automatic Interaction Detector and Quick, Unbiased, Efficient, Statistical Tree) to select the optimal combination. The optimal model and clustering analysis were used to divide the patients into two groups (good and poor adherence), then the optimal decision algorithm was used to construct the prediction model of adherence and obtain its predictor variables.
Results
The results revealed that the RFm model, K-means clustering analysis and C5.0 algorithm were optimal. After three rounds of k-means clustering analysis, the optimal RFm clustering model quality was 0.8, 10614 elements were obtained, including 9803 and 811 from patients with good or poor adherence, respectively, and five types of patients were identified. The prediction model had an accuracy of 100% with the recent consultation month as an important adherence predictor variable.
Conclusions
This work presented a prediction model for medication adherence in AIDS patients at the designated AIDS center in Shanghai, using the RFm model and the k-means and C5.0 algorithms. The model can be expanded to include patients from other centers in China and worldwide.
A Comparison Of The Bridge-Type Roi-c Interbody Fusion Cage System And Titanium Mesh Graft With Titanium Plate Fixation In 2-Level Anterior Cervical Discectomy And Fusion With Plating And Cage System: A Retrospective Study
Authors: He Shuangjun , Zhou Zhangzhe , Shao Xiaofeng , Zhang Changhao , Zhou Xinfeng , Wu Shuhua , Chen Kangwu , Wang Yaowei , Zhonglai Qian
Published: July 2020

Objective: To explore the clinical efficacy and radioactive results of the bridge-type ROI-C interbody fusion cage (ROI-C) and anterior cervical discectomy and fusion with plating and cage system (ACDF) for cervical spondylopathy.Methods: From January 2014 to January 2018, 45 patients undergoing ACDF were retrospectively analyzed, including 24 cases of ROI-C (group A) and 21 cases of ACDF (group B). The operation time, blood loss, Neck Disability Index (NDI), Japanese Orthopaedic Association score (JOA), postoperative complications, imaging results including cervical Cobb angle and fusion were compared between groups.Results: All patients were successfully treated with surgery, and no cerebrospinal fluid leakage, esophageal fistula, or hoarseness occurred after surgery. The operation time and blood loss in group A were lower than those in group B (P<0.05). During the follow-up period, JOA score increased and NDI score decreased after operation (P<0.05), but there was no significant difference between the groups (P>0.05). The incidence of dysphagia in group A was lower than that in group B at 1 month and 3 months after operation (P<0.05), but the final follow-up results showed that there was no significant difference in the incidence of dysphagia between the two groups (P>0.05). In group A, the fusion rate was 83.3% 3 months after surgery and 100% at the last follow-up. The rate of adjacent level ossification development was 12.5%. In group B, the fusion rate was 85.7% 3 months after surgery and 100% at the last follow-up. The rate of adjacent level ossification development was 23.8%.Conclusion: Both ROI-C and ACDF can achieve satisfactory results, but ROI-C has shorter operation time, less bleeding and lower incidence of dysphagia in the short term.
BTG1 Inhibits Malignancy as a Novel Prognosis Signature in Endometrial Carcinoma
Authors: Li Yibing , Huo Jianing , He Junjian , Zhang Yunzheng , Ma xiaoxin
Published: July 2020

Background: Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC.Methods: Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot.Results: We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs.Conclusions: BTG1 plays an important role in the occurrence and development of EC. BTG1, as a tumor suppressor gene, shows low expression in EC, which can inhibit malignant biological behavior and EMT process of ECCs. In addition, BTG1 can be used as a potential prognostic biomarker for EC.
Overexpression of BNIP3 in Rat Intervertebral Disc Cells Can Trigger Autophagy-Related Apoptosis
Authors: Wu Ting-Sheng , Fan Shao-Yong , Zhang Bin , Tao Zhi-Qiang , Hua Hong , Dai Min
Published: July 2020

Background: Intervertebral disc degeneration (IDD) is the important cause of low back pain. Excessive apoptosis of intervertebral disc cells is the primary cause of IDD. BNIP3 is a member of Bcl-2 family and is widely involved in cell autophagy and apoptosis. However, the roles and mechanisms of BNIP3 in intervertebral disc cell autophagy and apoptosis are unclear.Results: In this study, the primary rat intervertebral disc cells were prepared and applied to study the effect of BNIP3 overexpression on their autophagy and apoptosis. RT-PCR and western blotting assay showed that BNIP3 overexpression significantly up-regulated the expression of autophagy and pro-apoptotic related proteins, including HIF-1α, Apaf-1, cleaved caspase 3, LC-3 and Beclin-1, while down-regulated the expression of anti-apoptotic protein Bcl-2. Subsequent cell staining detection of autophagy and apoptosis showed that BNIP3 overexpression significantly increased the autophagy and apoptosis of rat intervertebral disc cells. Furthermore, BNIP3 interference assay revealed that the effects of BNIP3 overexpression can be reversed by BNIP3 interference. Conclusions: The above findings suggested that BNIP3 enhanced autophagy of intervertebral disc cells and further triggered the apoptosis of intervertebral disc cells, eventually led to the development of intervertebral disc degeneration.
Thrombolysis with intra-arterial urokinase for acute superior mesenteric artery occlusion: Outcome analysis
Authors: Lin Being-Chuan , Wu Cheng-Hsien , Wong Yon-Cheong , Hung Sheng-Che , Hsin Ming-Che
Published: July 2020

Background

The aim of this study was to evaluate the outcome of intra-arterial urokinase thrombolysis for acute superior mesenteric artery (SMA) occlusion.
Methods

Ten patients with acute SMA occlusion who underwent intra-arterial urokinase therapy between 2008 and 2019 were retrospectively evaluated.
Results

Among the 10 patients, 7 were men and 3 were women (median age, 75.5 years). The median time from onset of abdominal pain to emergency department admission was 11 hours (interquartile range [IQR], 4.9 hours). None of the patients presented with shock in the triage screening or acute peritonitis on physical examination, and 4 (40%) had bloody stools. On angiography, 6 patients presented with complete SMA occlusion and the other 4 patients had incomplete occlusion. The median time from abdominal pain to attempting urokinase thrombolysis was 15.5 hours (IQR, 8.0 hours). During the course of the urokinase therapy, all the patients showed various degrees of recanalization (near-total, n = 2; partial, n = 8) on follow-up angiography. The median urokinase therapy duration was 39.0 hours (IQR, 48.0 hours). After urokinase therapy, bowel perfusion was restored with bowel preservation in 4 patients; however, in the other 6 patients, bowel perfusion was not restored. Comparison between the 4 patients with restored bowel perfusion and 6 patients with unrestored bowel perfusion revealed that the degree of SMA occlusion was statistically significant (complete vs. incomplete, p = 0.012). Of the 6 patients with complete SMA occlusion, 5 underwent bowel resection, of whom 2 died, and the remaining patient died of shock due to delayed surgery. Of the 4 patients with incomplete SMA occlusions, no bowel resection was performed except a partial omentectomy. Of the 3 deaths, one was attributed to delayed surgery, and the other two developed short bowel syndrome with sepsis and multiple-organ failure, with a 30% in-hospital mortality rate. The median hospital stay was 20.0 days (IQR, 32.0 days).
Conclusion

In our experience, thrombolysis with intra-arterial urokinase may serve as an adjunctive treatment modality to preserve the bowel and obviate surgery for incomplete SMA occlusion. However, it was not suitable for complete SMA occlusion, which requires surgery.