bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)
Authors: KORANG STEVEN KWASI , Juul Sophie , Nielsen Emil Eik , Feinberg Joshua , Siddiqui Faiza , Klingenberg Sarah , Bu Fanlong , Thabane Lehana , Thomsen Allan Randrup , Jakobsen Janus C , Gluud Christian
Published: July 2020

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes corona virus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19.Methods/design: We will conduct a living systematic review based on searches of major medical databases (e.g. MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; ‘active placebo’; no intervention; standard care; an ‘active’ intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analyses, and individual patient data meta-analyses. Risk of bias will be assessed with domains, our eight-step procedure to assess if the thresholds for clinical significance are crossed, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) will assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and analyzed separately. Discussion: COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease.Systematic review registration: PROSPERO CRD42020196492
Postural Control is Associated with Functionality and Cell Health in Elderly.
Authors: BERTOLINI GIOVANA , Silva Bruna Spolador de Alencar , Santos Vanessa Ribeiro dos , Messias Iracimara de Anchieta , Marini Elisabetta , Gobbo Luís Alberto
Published: July 2020

Background: Alterations in cellular health and postural control occur with aging and contribute to the increased risk of falls.The aim of this study was to analyse the relationship between static balance in relation to functionality and cell health. Methods: We evaluated 21 elderly people of both sexes, aged ≥60 years (11 men: 77 ± 9 years; 10 women: 74 ± 10 years) . The ability and quality of maintaining balance in standing posture measured by the movement of the pressure center (CoP) for seven positions: feet separated open and closed eyes (FSEO, FSEC), feet together open and closed eyes (FTEO, FTEC), semi-tandem open and closed eyes (STEO, STEC), and one-legged-support (OLS). Cellular health was measured by means of electrical bioimpedance (BIA) and functionality through the Timed Up and Go Test (TUG) and Short Physical Performance Battery (SPPB). Results: In the analysis of the mediolateral velocity of the positions FSEO, FSEC, FTEC, and STEO on the platform, an inverse correlation between balance and bioelectrical impedance variables were verified for all models, with a coefficient of explanation (r2) varying between 20% (resistance in FSEO position) and 74% (reactance in STEO position, Model 3). Inverse and significant correlations between reactance and phase angle in the OLS position was verified, in all adjustment models, with coefficient of explanation varying between 62% (phase angle, OLS area, Model 1) and 91% (same variables, Model 3). In the analysis of mediolateral velocity for the STEC position, positive correlation with TUG and an inverse correlation with reactance, resistance, phase angle were observed, with coefficient of explanation varying between 21% (resistance, Model 1) and 67% (reactance, Model 3).Conclusions: The postural control is linearly related to bioimpedance parameters and functionality in elderly. The assessment of balance can provide important information on the health condition of the elderly, and furnishes useful insights for prevention and treatment strategies.
Clinical Experience with Fetal Sex Chromosome Aneuploidy Identified by Non-Invasive Prenatal Testing in 45773 Cases
Authors: Lu Xinran , Wang Chaohong , Sun Yuxiu , Tang Junxiang , Tong Keting , Zhu Jiansheng
Published: July 2020

Objective: To investigate the positive predictive value (PPV) and clinical features of non-invasive prenatal testing (NIPT) as a screening method in detecting sex chromosome aneuploidy (SCA) within a high-risk population at the Maternity and Child Health Hospital of Anhui Province.Methods: From June 2015 to June 2019, 45773 women with singleton pregnancies volunteered to take an NIPT. Cell-free fetal DNA was extracted for high-throughput sequencing and amniocentesis karyotype analysis was performed in pregnant women. Results: 314 high-risk pregnant women underwent NIPT and 143 chose invasive prenatal diagnosis. Karyotype analysis was performed in amniotic fluid cells, wherein 7 cases of 45,X (PPV: 12.50%), 16 cases of 47,XXX (PPV: 55.17%), 25 cases of 47,XXY (PPV: 71.43%), and 10 cases of 47,XYY(PPV: 76.92%) were confirmed. The PPV of NIPT for SCA was 40.56%. The rate of SCA detected in women aged 40 years and older was 0.39%, which was significantly different from that detected in women aged <30, 30–34, and 35–39 years (P < 0.05). The detection rates of 47,XXX and 47,XXY were significantly correlated with maternal age (P < 0.05), but those of 45,X and 47,XYY showed no significant correlation with maternal age.Conclusion: NIPT can be applied for the detection of SCA, but the detection accuracy is low. Genetic counseling and further prenatal diagnosis should be provided.
Total Cholesterol, Alanine Aminotransferase And the Risk of Primary Liver Cancer: A Population-based prospective study
Authors: Sun Miaomiao , Wang Wanchao , Liu Xining , Wang Yiming , Cui Haozhe , Liu Siqing , Cao Liying
Published: July 2020

Background: Previous studies have shown that serum total cholesterol(TC) and serum alanine aminotransferase(ALT) were associated with liver cancer risk, respectively. However, the common contribution of TC and normal-high ALT to primary liver cancer(PLC) has not been reported to date. We aim to assess the separate and joint effect of low TC level and normal-high ALT level on the risk of PLC, a large prospective cohort was conducted in our study.Methods: The participants were divided into 4 groups via cross-matching method according to TC[low level(-)/ non-low level(+)] and ALT[normal level(-)/ normal-high level(+)] status, and using the lower quartile(P25) value(4.24 mmol/L) of TC and the upper quartile(P75) value(22 U/L) of ALT as a threshold, respectively. Incident PLC was confirmed by review of medical records. Cox proportional hazards regression models and interactive additive models were used to evaluate whether the joint effect of low TC level and normal-high ALT level is associated with the risk of PLC.Results: During 1,248,895 person-years follow-up, 298 participants were diagnosed with PLC among 114,972 subjects. TC＜4.24 mmol/L for the “TC(-)” group; TC≥4.24 mmol/L for the “TC(+)” group; ALT＜22U/L for the “ALT(-)” group; ALT≥22U/L for the “ALT(+)”. Compared with the “TC(+)” group, “ALT(-)” group, respectively, the adjusted hazard ratio(HR) and 95% confidence interval(95%CI) for PLC risk was 1.71 (1.34-2.19) in “TC(-)” group and for PLC risk was 1.52 (1.18-1.95) in “ALT(+)” group. In combinatorial analysis, compared with “TC(+) and ALT(-)” group, the significant increased risk of PLC were observed in “TC(+) and ALT(+)” group (HR=1.45; 95%CI: 1.07-1.97), “TC(-) and ALT(-)” group(HR=1.64; 95%CI: 1.21-2.22) and “TC(-) and ALT(+)” group(HR=2.70; 95%CI: 1.84-3.96), respectively. The interaction between “TC(-)” and “ALT (+)” on the risk of PLC was not significant(Pinteraction=0.26). Conclusions: Both low TC level and normal-high ALT level were risk factors of PLC. There is the separate and joint effect of low TC level and normal-high ALT level on the risk of PLC.Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered)
Optimization of Epicardial Fat Thickness Change in Obese Patients with Weight Loss by Bariatric Surgery Using Central Composite and Box-Behnken Design
Authors: Elmalı Ferhan , Tekindal Mustafa Agah , Altın Cihan , Ateş Can , Erol Varlık
Published: July 2020

Background: The aim of our study was to determine the optimization of the change in epicardial fat thickness in obese patients who underwent bariatric surgery with Central Composite (CCD) and Box-Behnken Experimental design (BBD). Methods: Response Surface Methods are used to see the sensitivity of the assessment criterion to changes in design variables, and even to obtain the necessary correlations experimentally. Response surface methods are evaluated in two different ways as CCD and BBD design. In this study, 33 experimental designs were designed. The study data consisted of 40 obese patients who lost weight by bariatric surgery between February 2015 and December 2016. Body Mass Index (BMI), Age and HOMA values were evaluated in 3 categories and 3 levels, and response variable was the change in Epicardial Fat Thickness (ΔEFT). Results: As a result of CCD analysis, Age = 30.52, BMI = 45.30, HOMA = 34.62, the optimum ΔEFT = 2.571. As a result of BBD analysis, Age = 38.36, BMI = 63.18, HOMA = 14.95, the optimum ΔEFT = 3.756. Optimum ΔEFT is modeled with Contour and Response surface graphics. Conclusion: According to the results of the analysis, it was found that BBD analysis for optimum ΔEFT was more positive than CCD and optimum age, BMI and HOMA combinations were determined to reach maximum ΔEFT.
Anti-melanoma-associated Antigen A1 Autoantibodies Predict the Outcome of Patients With Idiopathic Inflammatory Myopathies Related Interstitial Lung Disease
Authors: Shen Yawen , Jiang Wei , Yang Hanbo , Chen He , Peng Qinglin , Wang Yanan , Yang Heng , Wang Guochun , Lu Xin
Published: July 2020

Background

The discovery of novel autoantibody in patients with idiopathic inflammatory myopathies (IIMs) is of great significance for clinical subtype stratification and potential pathogenesis. Previous literatures have found that tumor-associated antigens were involved in the pathogenesis of IIM. Therefore, in this study, we aimed to explore the prevalence and clinical association of autoantibodies against melanoma-associated antigen A1 (MAGE-A1) in patients with IIM.
Methods

ELISA was performed to detect anti-MAGE-A1 autoantibodies in patients with IIM, systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren syndrome, systemic sclerosis, and healthy controls, and the results were confirmed using the dot-immunoblotting assay. The association between anti-MAGE-A1 autoantibody and clinical characteristics was analyzed in IIM patients. T test, Mann-Whitney U test, double-sided Pearson's Chi-square, Fisher exact test, Spearman correlation analysis as well as the generalized estimating equation were applied in the statistical analyses.
Results

Anti-MAGE-A1 autoantibodies were detected in 5.03% (29/576) of all IIM patients, 4.60% (18/390) of dermatomyositis, 7.20% (5/69) of amyopathic dermatomyositis, and 5.10% (6/117) of polymyositis/immune-mediated necrotizing myopathy patients. The frequency of interstitial lung disease (ILD) was higher in anti-MAGE-A1-positive patients than those in anti-MAGE-A1-negative ones (82.8% vs 55%, p = 0.003). Anti-MAGE-A1-positive patients with IIM associated ILD had less dyspnea, more commonly asymptomatic ILD, and higher percentage of force vital capacity and diffusing lung capacity of carbon monoxcide of predicted values when compared to negative ones. The anti-aminoacyl-tRNA synthetase (ARS) coexisting anti-MAGE-A1-positive patients had common monocyclic disease course, while only anti-ARS-positive and anti-ARS coexisting anti-Ro52-positive patients had a more polycyclic disease course. None of anti-ARS-positive patients coexisting anti-MAGE-A1 antibody died during 10-year follow-up evaluation.
Conclusion

Anti-MAGE-A1 is a novel autoantibody associated with ILD in IIM patients. Anti-MAGE-A1-positive IIM patients with ILD appear to have good prognosis. Detection of anti-MAGE-A1 autoantibody may be useful in predicting the outcome of IIM patients with ILD.
Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension
Authors: Yiangou Andreas , Mitchell James , Vijay Vivek , Grech Olivia , Bilton Edward , Lavery Gareth , Fisher Claire , Edwards Julie , Mollan Susan , Sinclair Alexandra
Published: July 2020

BackgroundThe mechanisms driving headache in Idiopathic Intracranial Hypertension (IIH) are not fully understood. Headache is the dominant driver for disability and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet need.Case seriesWe report seven patients with confirmed IIH who initially presented with increased headache driven by raised intracranial pressure (ICP). The headaches had migraine-like characteristics which persisted despite resolution of papilloedema (ocular remission). These headaches responded markedly to Erenumab, a monoclonal antibody targeted against the calcitonin gene related peptide (CGRP) receptor. Importantly, there was a recurrence of raised ICP and papilloedema, however headaches did not recur whilst treated with Erenumab.ConclusionsThese cases suggest that CGRP could be a mechanistic driver for headache in patients with active IIH. Clinical trials evaluating safety and efficacy of CGRP monoclonal antibodies in active IIH would be of interest.
Primary pleural squamous cell carcinoma accompanied by a big pulmonary bulla in a 68-year-old man: a case report and literature review
Authors: Zhong Chuan , Zhou Haining , Rami-Porta Ramón , Zhao Yunfei
Published: July 2020

Background: Primary pleural squamous cell carcinoma is extremely rare. Its incidence is not described in the literature, and the cause of this disease is unclear due to its rarity. Case presentation: We present the rare case of primary pleural squamous cell carcinoma in a 68-year-old man with a big pulmonary bulla who undergone en bloc complete resection of both lesions. Two months after surgery, the patient received radiation therapy over the operative field to a total dose of 50Gy. More than a year after completion of treatment, the patient is well and in complete remission. Conclusions: To the best of our knowledge, this is the first case of primary pleural squamous cell carcinoma with a big pulmonary bulla. Complete surgical resection combined with radiation therapy was proposed for therapeutic purposes. Toinvestigate long-term prognosis of this disease, further more cases are needed.
The comparison of the functional outcomes between primary closure and reconstruction with free flap after resection of T1 stage tongue cancer: A prospective study
Authors: Pathak Ajit Kumar , Wu Xiaoshan , Yang Rong , Long Huang , Xiong Yafei , Pradhan Pralab , Guo Feng
Published: July 2020

Background: Reconstruction with free flap after the resection of tongue cancer is commonly used by craniofacial surgeons. However, it is unknown whether the reconstruction with free flap is better than the primary closure for the T1 stage tongue cancer. The objective of this prospective study is to compare the functional outcomes between these two methods.Methods: In this prospective study, 30 patients who were diagnosed as T1 stage tongue cancer (on anterior -two third of the tongue) were randomly divided into two groups. The first group underwent the primary closure after the resection (15 patients) and the second group were reconstructed with the anterolateral perforator flap (15 patients). All patients underwent postoperative functional evaluation using specific questionnaires and a screening test with special emphasis on speech, swallowing, and tongue mobility at 1, 3, 6 and 12 months.Results: Functional outcomes, including tongue mobility, speech, and swallowing, were all better in primary closure than anterolateral thigh flap group. At 1-month post-op, the speech understandability of the patients who received a primary closure were statistically better than those who received ALT flap (p = 0.01), while at 1-year post-op, there was no significantly different on speech understandability between two groups (p = 0.16). Statistically significant differences were found between the two groups in the swallowing capacity at all four different time periods (p < 0.05). For the primary closure group, tongue mobility was statistically better at all four different time periods than in ALT flap group (p < 0.05).Conclusion: For the tongue cancer patients (T1), reconstruction with primary closure, rather than with flap, can reserve more functions including tongue mobility, speech and swallowing outcomes, and therefore might be the appropriate reconstruction method after partial glossectomy.
Debulking mastectomy with electrochemotherapy: a case report of no surgery approach to recurrent breast cancer.
Authors: Esposito Emanuela , Siani Claudio , Pace Ugo , Costanzo Raffaele , Giacomo Raimondo di
Published: July 2020

Background Electrochemotherapy has been shown to be safe, effective and non-invasive loco-regional treatment for chest wall breast cancer recurrence. Electrochemotherapy is the gold standard treatment of patients with cutaneous metastases from breast cancer who due to the extent of those lesions are not eligible for resection or radiotherapy has already been used, and systemic therapy is ineffective or contraindicated. Case presentation Here we present the case of a women affected by multiple metastatic cancers with multi-drug resistance who refused mastectomy after being diagnosed with recurrent ulcerated right breast cancer. We first describe an extended indication to electrochemotherapy to treat breast cancer recurrence after breast conserving surgery. Electroporation-induced necrosis through electrochemotherapy replaced surgery and was delivered in 30 minutes at 5000 Hz frequencies at 730 V by hexagonal needle under general anesthesia. The necrosis of the remaining breast resulted in a voluminous eschar that was easily removed few months after leaving the chest wall free from macroscopic disease turning in a non-surgical mastectomy. Conclusions. This kind of breakthrough application of electrochemotherapy might be considered to avoid palliative mastectomy in very selected patients. New technologies may help clinicians to find agreement between patient’ will and the burden of treatment and might contribute in selected cases to give options to patients not keen on having surgery.
Is Robot-assisted Radical Cystectomy the Preferred Minimal Invasive Procedure for Non-advanced Bladder Urothelial Carcinoma(T1-T2N0M0)? A Single Center Retrospective Study.
Authors: Xiao Ming , Zhong Zhaohui , Ren Jiannan , Xiong Wei
Published: July 2020

Background: To investigate the perioperative efficacy and cost of robot-assisted radical cystectomy(RARC) and laparoscopic RC(LRC) in patients with non-advanced bladder urothelial carcinomaMethods: 156 patients with non-advanced bladder urothelial carcinoma undergoing minimally invasive radical cystectomy in our center between January 2015 and April 2020 were included. Perioperative data and hospitalization expenses were extracted from our database. All analyses were performed using SPSS 23.0 software, and p < 0.05 was considered statistically significant.Results: The proportion of male patients was 86.5%(135/156) and the median age was 65(IQR 59-71) years old. RARC had a lower PSM rate (0 vs 5.3%,P=0.051), longer median operation time(370 vs 305 min,P<0.001) and higher median hospitalization cost(20565.2 vs 15532.4$,P<0.001). There were no significant differences in intraoperative transfusion rate, anesthesia resuscitation in ICU, postoperative hospital stay, 30-d complications and postoperative treatment expenses between the two groups(P=0.815,0.715, 0.817,0.92 and 0.543,respectively.)Conclusion: Short operation time and low hospitalization costs are favorable factors for LRC, but RARC may be the preferred surgical procedure for non-advanced bladder urothelial carcinoma considering the potentially low PSM rate.Trial registration: A complete informed consent was obtained from the patient and their families before the surgery.Informed consent was signed for all patients.This study was approved by the Ethics Review Committee of the Second Xiangya Hospital of Central South University
A Standard Set of Outcome Measures for the Comprehensive Assessment of Osteogenesis Imperfecta.
Authors: Nijhuis Wouter , Franken Anton , Ayers Kara , Damas Chantal , Folkestad Lars , Forlino Antonella , Fraschini Paolo , Hill Claire , Janus Guus , Kruse Richard , Wekre Lena , Michiels Lieve , Montpetit Kathleen , Panzeri Leonardo , Porquet-Bordes Valerie , Rauch Frank , Sakkers Ralph , Salles Jean-Pierre , Semler Oliver , Sun Jony , To Michael , Tosi Laura , Yao Yangyang , Yeung Eric Hiu Kwong , Zhytnik Lidiia , Zillikens Carola , Verhoef Marjolein
Published: July 2020

Background: Osteogenesis Imperfecta (OI) is a genetic disorder of collagen type I, also known as ‘brittle bone disease’. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes making comparison of outcomes available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future. Methods: The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. This consensus method was based on data derived from the OI community and used focus groups, expert opinions and a literature search to determine the domains that matter most to people with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search. 16 focus groups (9 with adult and 7 with children) as well as multiple discussions and further Delphi rounds with the Key4OI working group were held to reach a consensus on a minimal set of outcomes and measuring instruments.Results: More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults. Conclusion: The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set.
Nutrient Patterns and Their Relation With Obesity in Iranian Adults: A Population-based Study
Authors: Amini Mohammad Reza , Akbarzade Zahra , Djafari Farhang , Yarizadeh Habib , Shahavandi Mahshid , Sheikhhossein Fatemeh , Payande Nastaran , Djafarian Kurosh , Shab-Bidar Sakineh
Published: July 2020

Objective: In spite of growing evidence on the associations between nutrient patterns and obesity. A few study examined the association between patterns of nutrient intake and obesity we aimed to explore the association between nutrient pattern and obesity in Iranian adults.Results: In this cross-sectional study, a total of 850 subjects aged years 20 to 59 were randomly selected. Our statistical analysis revealed three major nutrient patterns that show the principle factor loading of nutrient intake. We observed a significant association between quintiles in men for Fasting Blood Sugar (FBS) (P<0.006) in the first nutrient pattern. Moreover, we identified a significant difference between quintiles in the first nutrient pattern in women for obesity (P=0.007), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (P<0.02). In the third nutrient pattern, we identified a significant association for SBP in women (P<0.02).
A Capacity-building Pilot Program to Increase Critical Care Research Productivity in the Middle East Region
Authors: Nazer Lama , Kleinpell Ruth , Olsen Keith , Hawari Feras
Published: July 2020

Objective

Though research is well established in the developed world, it lags behind in developing countries. We describe a multi-disciplinary, structured, mentor-based program that aimed to improve research skills and increase research productivity among critical care practitioners in the Middle East region.
Results

The program was conducted between October 2016 and September 2017, and enrolled 11 critical care practitioners (5 pharmacists and 6 physicians) with minimal research experience from 5 countries (Jordan, Saudi Arabia, Oman, Egypt, and Sudan).The program addressed three major factors that contribute to low research productivity in developing countries which include: lack of research knowledge and skills, lack of mentorship, and poor preparation of manuscripts. It started with a research proposal workshop and ended with a manuscript writing workshop, with monthly webinars throughout the year about research-related topics. The faculty consisted of 10 clinical instructors, among whom 7 also served as mentors, a biostatistician, and a medical editor. By the end of the program, 7 research projects and 5 manuscripts were completed. According to the program evaluation, participants agreed that the program improved their research skills and the quality of their research.
Effect of Dapsone Alone and in Combination With Intracellular Antibiotics Against the Biofilm Form of B. Burgdorferi
Authors: Horowitz Richard Ira , Murali Krithika , Gaur Gauri , Freeman Phyllis R. , Sapi Eva
Published: July 2020

Objective
Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses.
Results
Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi.
Identification of drug targets and potential molecular mechanisms of Wantong Jingu Tablet in treatment of rats with collagen-induced arthritis based on 16S rDNA high-throughput sequencing and metabolomic analysis
Authors: Li Zhaodong , Qi Fangyuan , Li Fan
Published: July 2020

Background: Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, can reduce the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism is unclear. The aims of this study were to investigate the therapeutic mechanisms of WJT for RA in vivo.Methods: The effects of WJT on the joint pathology, and the levels of Bax, Bcl-2,caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were demonstrated based on several experiments in the model of collagen-induced arthritis (CIA) in rats. 16S rDNA high-throughput sequencing was used to investigate the effect of WJT on the overall structure and composition of gut microbiota. Meanwhile, metabolite changes in faeces were analyzed by metabolomics techniques.Results: The results showed that WJT restored the joint pathology in CIA rats, upregulated Bax and cleaved-caspase-3, downregulated Bcl-2, caspase-3, and pERK1/2, and reduced the levels of pro-inflammatory cytokines. The overall gut microbial structure in CIA rats was altered after WJT treatment. Three bacterial phyla were prominently restored: Bacteroidetes,Tenericutes and Deferribacteres, and three bacterial genera were significantly reversed: Vibrio, Macrococcus and Vagococcus. Furthermore, five specific metabolites associated with these specific bacterial genera were identified by correlation analysis. In addition, WJT supplement trended to down-regulate the other five metabolites according to metabolomic analyses.Conclusions: These results revealed that WJT restored the pathological changes of RA might through activating the mitochondrial apoptosis pathway, inhibited MEK/ERK signaling, and modulating the special bacteria and the special metabolites.Keywords: Rheumatoid arthritis; 16S rDNA high-throughput sequencing; metabolomics; drug targets; Wantong Jingu Tablet
Safety of Endovascular Treatment for Concomitant Unruptured Intracranial Aneurysms and Cerebral Vascular Stenosis
Authors: Jin Hengwei , Wang Jing , Meng Xiangyu , Li Youxiang , Miao Zhongrong , He Hongwei
Published: July 2020

Background

To evaluate the safety of endovascular therapy for concomitant unruptured intracranial aneurysms (UIAs) and cerebral vascular stenosis.

Methods

Patients between January to August 2019 were retrospectively reviewed at our institution. Concomitant UIA and cerebral vascular stenosis patients underwent endovascular treatment were included. The demographics and clinical information were collected. Patients were divided into 4 groups according to lesions that was treated (aneurysm, stenosis, both lesions in a single session or in separated sessions). Patients were divided into another 2 groups based on locations of aneurysm and stenosis (ipsilateral and non-ipsilateral). The demographics and clinical data were compared among groups.

Results

A total of 105 (4.9%) cases have concomitant UIA and cerebral vascular stenosis. Eighty-one patients underwent endovascular treatment for the stenosis(n=18), aneurysm(n=41) or both lesions (one session=10; separated sessions n=12). Seven (8.6%) patients experienced procedural related complications, including 1 (1.2%) hemorrhagic and 6 (7.4%) ischemic types. In terms of procedures, 4 (6.3%) complications is related with UIA embolization, 2(5.0%) related with intracranial stenosis angioplasty. Complication rate of patients underwent intracranial angioplasty and aneurysm embolization simultaneously is much higher (20%) than that of the other groups (5.6%-8.3%). Patients with ipsilateral lesions also had higher complication rate (11.1%) than non-ipsilateral patients (6.7%). Follow-up (74 patients, mean=6.5months) result showed good clinical outcome in 70 (94.6%) patients.

Conclusions

Simultaneous treatment for concomitant UIA and extracranial stenosis may not pose additional risks. Ipsilateral lesions and single session procedure for intracranial stenosis and UIA are potential risk factors for periprocedural complications.
Clinical Significance of Peripheral Blood-Derived Inflammation Markers in Advanced Gastric Cancer after Radical Resection
Authors: Gu Lihu , Chen Bangsheng , Zheng Dingcheng , Mo Jiahang , Yuan Lingling , Mao Feiyan , Zhang Kang , Ng Derry Minyao , Chen Ping , Wang Dongjie
Published: July 2020

Background and objective: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis.Methods: A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly.Results: The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR <154.Conclusions: Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.
LncRNA MONC Suppresses the Malignant Phenotype of Endometrial Cancer Stem Cells by Regulating the MiR-636/GLCE Axis
Authors: Li Yibing , Huo Jianing , He Junjian , Ma Haining , Ma Xiaoxin
Published: July 2020

Background: Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma (HNSCC), lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods: The expression of genes was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of proteins was detected by Western blot. The interplay of LncRNA-miRNA-mRNA was verified using the luciferase assay. The growth rate of ECSC spheroids was detected by sphere formation assay. Cell proliferation was detected by CCK-8 assay. The cell invasion was detected by transwell invasion assay. Cell cycle was detected by Cell cycle analysis.Cell apoptosis was detected by the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining assay. Animal study was conducted to evaluate the effect of MONC combined with miR-636 on tumor growth in vivo. Results: Low MONC expression in endometrial carcinoma (EC), which directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited the Notch signaling pathway and tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC, and this effect is more obvious in ECSC. Conclusion: MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. The MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.
Bronchioalveolar Stem Cells Derived from Mouse Induced Pluripotent Stem Cells Promote Airway Epithelium Regeneration
Authors: Kawakita Naoya , Toba Hiroaki , Miyoshi Keiko , Sakamoto Shinichi , Matsumoto Daisuke , Takashima Mika , Aoyama Mariko , Inoue Seiya , Morimoto Masami , Nishino Takeshi , Takizawa Hiromitsu , Tangoku Akira
Published: July 2020

Background: Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.Methods: BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engrafted BASCs on BADJ, and its ability to promote repair an injury to the airway epithelium, were evaluated.Results: Flow cytometric analysis revealed that BASCs represented ~7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs by using transmission electron microscopy showed that the cells containing secretory granules harboured microvilli and small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 d after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Conclusions: Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Notably, the differentiated iPSCs promoted airway epithelium at the BADJ in the mouse model of naphthalene-induced airway epithelium injury.
A Risk Scoring System to Predict Progression to Severe Pneumonia in Patients with Covid-19
Authors: Lee Ji Yeon , Nam Byung-Ho , Kim Mhinjine , Hwang Jongmin , Kim Jin Young , Hyun Miri , Kim Hyun Ah , Cho Chi-Heum
Published: July 2020

Rapid outbreak of coronavirus disease 2019 (Covid-19) raised major concern regarding medical resource constraints. We constructed and validated a scoring system for early prediction of progression to severe pneumonia in patients with Covid-19. A total of 561 patients from a Covid-19 designated hospital in Daegu, South Korea were randomly divided into two cohorts: development cohort (N=421) and validation cohort (N=140). We used multivariate logistic regression to identify four independent risk predictors for progression to severe pneumonia and constructed a risk scoring system by giving each factor a number of scores corresponding to its regression coefficient. We calculated risk scores for each patient and defined two groups: low risk (0 to 8 points) and high risk (9 to 20 points). In the development cohort, the sensitivity and specificity were 83.8% and 78.9%. In the validation cohort, the sensitivity and specificity were 70.8% and 79.3%, respectively. The C-statistics was 0.884 (95% CI, 0.833-0.934) in the development cohort and 0.828 (95% CI, 0.733-0.923) in the validation cohort. This risk scoring system is useful to identify high-risk group for progression to severe pneumonia in Covid-19 patients and can prevent unnecessary overuse of medical care in limited-resource settings.
Investigation of the renewable diseases in the Maiji Grottoes: some reflection for PVAc
Authors: Meng Chenglei , Shiqiang Fang , Qian Ma , Wenjing Hu , Xiaobin Liu , Ye Zheng , Guangqiang Dong , Yongqiang Yue , Bingjian Zhang
Published: July 2020

The Maiji Grottoes a famous grotto group located on the ancient “Silk Road”. It occupies a significant place in the history of grottoes and has also contributed to the communication of Buddhist art. Since the 1970s, the Chinese government and restoration professionals have made many efforts to restore the Maiji Grottoes for purposes of both scientific research and cultural protection. However, some severe diseases have repeatedly broken out in several grottoes, which require urgent treatment. In this paper, 21 grottoes and about 137.72 m2 of murals from 21 grottoes reinforced by PVAc emulsion were investigated. The results indicated the most common diseases are cracking, hollowing, discoloration, mildew, saline-alkaline and flaking. These diseases have a close relationship with the microenvironment of each grotto. Moreover, the LC analysis showed the PVAc look like remained practically the same reinforce effect, regardless of changes in time and climate. Thus, the PVAc could be used in the protection of murals for which a controlled environment should be provided to prevent these renewed diseases.
Design, Molecular Docking And In Silico Analysis Of Analogues Of Chloroquine And Hydroxychloroquine Against SARs-COV-2 Target (6w63.pdb)
Authors: Yakubu Naruka Solomon , Poyi Olanike Catherine , Afolabi Ezikiel Olabisi
Published: July 2020

Computer-aided drug design has been an effective strategy and approach to discover, develop, analyze, accelerate and economize design and development of drugs and biologically active molecules. A total of twelve analogues of chloroquine (CQ) and hydroxychloroquine (HCQ) were designed and virtually analyzed using PyRx software, Molinspiration, Swiss ADME, Swiss-Target Prediction software and ProTox-II-Prediction of toxicity platform. Based on the docking studies carried out using Autodock vina, five analogues; H-368 (-6.0 Kcal/mol), H-372 (--6.0 Kcal/mol), H-156 (-5.9 Kcal/mol), H-139 (-5.7 Kcal/mol), C-136 (-5.7 Kcal/mol) exhibited higher binding affinity compared to HCQ(-5.5 Kcal/mol), while all twelve analogues exhibited higher binding affinity compared to CQ (-4.5Kcal/mol). In silico analysis of toxicity profile of this analogues shows a lower potential to toxicity and a comparable activity on some major isoforms of cytochrome P450. But unlike the parent molecules, both H-139 and H-156 are substrates of P-glycoproteins (P-gp) which implies that these analogues possess high clearance and less pharmacokinetic-related drug-drug interactions compared to the parent molecules. Herein we propose these analogues as potential inhibitors or lead compounds against the coronavirus with a view of conducting more molecular dynamic simulations, synthesizing and conducting in vitro studies on them.
Förderung des Lernens durch soziale Hinweisreize in Lernmaterialien
Authors: Demuth Sabine , Dreiling Tanja , Ebnet Viktoria , Hausner Franz , Stiller Klaus Dieter
Published: July 2020

Soziale Hinweisreize sind wesentliche Komponenten aller Arten von Lernmaterialien. Sie umfassen verbale, nonverbale sowie paraverbale Reize als auch wechselseitig aufeinander bezogene Reizfolgen. Obwohl soziale Hinweisreize in Lernmaterialien schon seit längerem untersucht werden, ist ihre systematische Erforschung noch jung. Sie umfasst primär kognitive, motivationale, affektive und soziale Prozesse, welche durch die Verwendung sozialer Hinweisreize in Lernmaterial ausgelöst oder beeinflusst werden. Ein Schwerpunkt der empirischen Forschung liegt dabei schon länger auf sozialen Prozessen. Von sozialen Reizen wird dabei angenommen, dass sie den Lernprozess positiv beeinflussen, u.a. indem sie bei den Lernenden den Eindruck sozialer Präsenz einer (Lehr-)Person stimulieren, was in der Folge zu mehr Lernmotivation, mehr Lernen auf Verständnis und letztendlich besseren Leistungen in Lerntests führt. In diesem Beitrag bieten wir eine Klassifikation der Vielfalt an sozialen Hinweisreizen in Lernmaterialien allgemein an, skizzieren ihre Wirkung über soziale Prozesse auf das Lernen, fassen einschlägige empirische Belege zusammen und diskutieren vernachlässigte Aspekte sozialer Hinweisreize.
Assessing the effects of four SUDS scenarios on combined sewer overflows in Oslo, Norway: evaluating the low-impact development module of the Mike Urban model
Authors: Hernes Ragni R. , Gragne Ashenafi S. , Abdalla Elhadi M. H. , Braskerud Bent C. , Alfredsen Knut , Muthanna Tone M.
Published: July 2020

Paved surfaces, increased precipitation intensities in addition to limited capacity in the sewer systems, cause a higher risk of combined sewer overflows (CSOs). Sustainable drainage systems (SUDS) offer an alternative approach to mitigate CSO by managing the stormwater locally. Seven SUDS scenarios, developed based on the concept of effective impervious area reduction, have been implemented in the Grefsen catchment using the Mike Urban model. This study evaluated the hydrological performance of two SUDS controls (i.e. green roof (GR) and rain garden (RG)) modules of the model and the effect of the SUDS scenarios on the CSOs using event-based and continuous simulations. The Nash–Sutcliffe efficiency (NSE) along with flow duration curves (FDCs) has been used for evaluating the model performance. Event-based evaluations revealed the superior performance of the RG in reducing CSOs for larger precipitation events, while GRs were proven to have beneficial outcomes during smaller events. The study illustrated another way of assessing the continuous simulations by employing the FDCs. The FDCs were assessed against a discharge threshold at the outlet (which authorities can set as design criteria) of the catchment in terms of the extent, each scenario reduced occurrence and duration of outflow that invokes flow in the overflow pipe.