bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Efficacy and Safety of Intravenous Remdesivir in Adult Patients with Severe Pneumonia caused by COVID-19 virus Infection: study protocol for a Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre trial
Authors: Horby Peter W , Cao Bin , Wang Yeming , Wang Chen 
Published: April 2020

Abstract
Background: A novel coronavirus emerged in Wuhan, Hubei Province, China towards the end of 2019 (SARS-CoV-2 or COVID-19 virus). Large scale spread within China and internationally led the World Health Organisation to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in-vitro and in-vivo experiments. It is also inhibitory against the COVID-19 virus in-vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe pneumonia caused by COVID-19 virus infection.Methods: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥18 years) with laboratory confirmed COVID-19 virus infection, and severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenous remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required had been observed.Discussion: This is the first randomized, placebo-controlled trial in 2019-nCoV. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.Trial registration: ClinicalTrials.gov, NCT04257656, 6th February 2020.
Identification and genetic analysis of qCL1.2 , a novel allele of the “green revolution” gene SD1 from wild rice ( Oryza rufipogon ) that enhances plant height
Authors: Zhang Lizhen , Huang Jingfen , Wang Yanyan , Xu Rui , Yang Ziyi , Zhao Zigang , Liu Shijia , Tian Yunlu , Zheng Xiaoming , Li Fei , Wang Junrui , Song Yue , Li Jiaqi , Cui Yongxia , Zhang Lifang , Cheng Yunlian , Lan Jinhao , qiao weihua , Yang Qingwen 
Published: April 2020

Abstract
Background: The exploitation of novel alleles from wild rice that were lost during rice cultivation could be very important for rice breeding and evolutionary studies. Plant height (PH) was a target of artificial selection during rice domestication and is still a target of modern breeding. The “green revolution” gene semi-dwarf 1 (SD1) were well documented and used in the past decades, allele from wild rice could provide new insights into the functions and evolution of this gene.Results: We identified a PH-related quantitative trait locus, qCL1.2, from wild rice using a set of chromosome segment substitution lines. qCL1.2 encodes a novel allele of SD1 gene. The wild allele of SD1 is a dominant locus that can significantly promote rice internode length by regulating the expression levels of genes involved in gibberellin biosynthesis and signal transduction. Nucleotide diversity and haplotype network analyses of the SD1 gene were performed using 2,822 rice landraces. Two previously reported functional nucleotide polymorphisms clearly differentiated japonica and indica rice; however, they were not associated with PH selection. Other new functional nucleotide polymorphisms in the coding, but not promoter, regions were involved in PH selection during rice domestication. Our study increases understanding of the rice SD1 gene and provides additional evidence of this gene’s selection during rice domestication.Conclusions: Our findings provide evidence that SD1 gene from wild rice enhances plant height and new functional nucleotide polymorphisms of this gene were artificially selected during cultivated rice differentiation.
Improvement in Circulating Endothelial Progenitor Cells Pool After Cardiac Resynchronization Therapy: Increasing the List of Benefits
Authors: Cristóvão Gonçalo , Milner James , Sousa Pedro , Ventura Miguel , Cristóvão João , Elvas Luís , Paiva Artur , Gonçalves Lino , Ribeiro Carlos Fontes , António Natália 
Published: April 2020

Abstract
Background Recent studies suggest that circulating endothelial progenitor cells (EPCs) may influence the response to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the effect of CRT on EPCs levels and to assess the impact of EPCs on long-term clinical outcomes. Population and methods Prospective study of 50 patients submitted to CRT. Two populations of circulating EPCs were quantified previously to CRT implantation: CD34 + KDR + and CD133 + KDR + cells. EPCs levels were reassessed 6 months after CRT. Endpoints during the long-term follow-up were all-cause mortality, heart transplantation and hospitalization for heart failure (HF) management. Results The proportion of non-responders to CRT was 42% and tended to be higher in patients with an ischemic vs non-ischemic etiology (64% vs 35%, p=0.098). Patients with ischemic cardiomyopathy (ICM) showed significantly lower CD34+KDR+ EPCs levels when compared to non-ischemic dilated cardiomyopathy patients (DCM) (0.0010 ± 0.0007 vs 0.0030 ± 0.0024 cells/100 leukocytes, p=0.032). There were no significant differences in baseline EPCs levels between survivors and non-survivors nor between patients who were rehospitalized for HF management during follow-up or not. At 6-month follow-up, circulating EPCs levels were significantly higher than baseline levels (0.0024 ± 0.0023 vs 0.0047 ± 0.0041 CD34 + KDR + cells/100 leukocytes, p=0.010 and 0.0007 ± 0.0004 vs 0.0016 vs 0.0013 CD133 + /KDR + cells/100 leukocytes, p=0.007). Conclusions Patients with ICM showed significantly lower levels of circulating EPCs when compared to their counterparts. CRT seems to improve the pool of endogenously circulating EPCs and reduced baseline EPCs levels seem not influence long-term outcomes after CRT.
Socio-demographic Determinants of Low Sexual Desire and Hypoactive Sexual Desire Disorder: A Population-based Study in Iran
Authors: Hamzehgardeshi Zeinab , Malary Mina , Moosazadeh Mahmood , Khani Soghra , Pourasghar Mehdi 
Published: April 2020

Abstract
Background: Various socio-demographic factors are determinants of Low Sexual Desire (LSD), but whether these are the determinants of Hypoactive Sexual Desire Disorder (HSDD) are unclear. The aim of this study is to evaluate the Socio-demographic determinants of LSD and HSDD in Iranian women of reproductive age.Methods: This was a population-based, cross-sectional study of 1000 Iranian women of reproductive age (15-49 years) who met the inclusion criteria and were chosen through systematic random sampling from all the healthcare centers in Sari, Iran. LSD was defined as a score no higher than 33 on the Sexual Interest and Desire Inventory-Female (SIDI-F); sexually related personal distress was defined as a score of at least 11.0 on the Female Sexual Distress Scale–Revised (FSDS-R); and HSDD was defined as a combination of these scores. Descriptive statistics were used to describe demographic characteristics while for analyzing grouped variables, chi-square test was applied. Multivariate regression test was also used to adjust the effect of confounding variables. Results: The mean score of sexual interest/desire among women who referred to healthcare centers in the city of Sari is estimated as 30.6±10.5. After adjusting the effect of the confounder variables by logistic regression multivariate analysis, the age at first intercourse, the length of time spent in marriage, and the level of satisfaction with income were variables significantly associated with LSD and HSDD (P < .01). Although increasing individual′s age (P < .001) and body mass index (P < .01) were predictors of LSD in women, HSDD was not statistically significant.Conclusion: There are some factors that are associated with LSD in women but are not related to HSDD. In other words, some factors associated with LSD do not cause personal distress which are one of the criteria necessary for HSDD.
Alleviating psychological distress associated with a positive cervical cancer screening result: a randomized control trial
Authors: Isaka Yukari , Hori Ai , Tanaka Rie , Ichikawa Masao 
Published: April 2020

Abstract
Background: The method of communicating a positive cancer screening result should seek to alleviate psychological distress associated with a positive result. We evaluated whether the provision of information through a leaflet would help reduce psychological distress.Methods: This study design was a simple randomized controlled trial that randomly assigned individual participants to the intervention and control groups and measured outcomes before and after the intervention. The analysis included 972 women. Women received hypothetical cervical cancer screening results, with a leaflet (intervention group) or without it (control group), randomly. Outcomes were psychological distress and intention to undergo further examination.Results: After the intervention, psychological distress appeared to be higher in the control group than in the intervention group among those who received a hypothetical positive screening result (odds ratio: 2.57, 95% confidence interval: 1.87–3.54), while 95% and 97% of those in the intervention and control groups, respectively, reported that they would undergo further examination.Conclusions: Information provision might help reduce psychological distress but not hinder further examination among women who screen positive for cervical cancer.Trial registration: UMIN Clinical Trials Registry UMIN000029894. Date of Registration: November 2017.
The Impact of Labor Stage Duration on Adverse Maternal and Neonatal Outcomes in Multiparous Women: A Retrospective Cohort Study
Authors: wang li , Wang hongxia , jia lu , qing wenjie , Li fan , Zhou Jie 
Published: April 2020

Abstract
Background The duration of first and second stages of labor was increased in the consensus that American College of Obstetricians and Gynecologists (ACOG) published 2014. Studies showed increased adverse maternal and neonatal outcomes in nulliparous women with prolonged second stage of labor. It is not very clear that the impact of labor stage duration on multiparous women.Methods A retrospective cohort study was performed. Cephalic, term, singleton multiparous women were included, who planned for vaginal delivery. Adverse maternal outcomes were defined as referral cesarean delivery, instrumental delivery, postpartum hemorrhage, perineal laceration (3rd and 4th degree), hospitalization stay ≥ 90%th, and adverse neonatal outcomes as NICU, shoulder dystocia, Apgar score ≤ 7(5 min), neonatal resuscitation, assisted ventilation required immediately after delivery. We defined the total stage included the first and second stage of labor.Results There were 7109 parturients included, The duration of first stage was 6.2(3.6–10.0) hours in multiparous women, the second stage was 0.3(0.2–0.7) hours, the total stage was 6.9(4.1–10.7) hours. In the first stage, the rate of overall adverse outcomes was 21%, 23.4%, 28.8%, 35.5%, 38.4% in < 6 h, 6-11.9 h, 12-17.9 h, 18-23.9 h, ≥ 24 h, increased significantly (X2 = 57.64, P๤0.001). Compared with < 6 h, ARR(95%CI) were 1.10(0.92,1.31), 1.33(1.04,1.70), 1.80(1.21,2.68), 2.57(1.60,4.15);In the second stage, the rate of overall adverse outcomes increased from 20.0%, 30.7%, 38.5%, to 61.2%, 69.6% in < 1 h, 1-1.9 h, 2-2.9 h, 3-3.9 h, ≥ 4 h (X2 = 349.70, P๤0.001). Compared with < 1 h, ARR (95% CI) were 1.89 (1.50, 2.39), 2.22 (1.55, 3.18), 10.64 (6.09, 18.59), 11.75 (6.55, 21.08); In the total stage, the rate of overall adverse outcomes were 21.5%, 30.8%, 42.4% in < 12 h, 12-23.9 h, ≥ 24 h (X2 = 84.90, P๤0.001). Compared with < 12 h, ARR (95% CI) were 1.41(1.16,1.72), 3.17 (2.10,4.80).Conclusions The prolonged labor stage may lead to increased adverse outcomes in multiparous women, even in the first stage. The duration of labor stage was an independent risk factor for adverse maternal and neonatal outcomes.
Intestinal barrier breakdown and mucosal microbiota disturbance in neuromyelitis optical spectrum disorder
Authors: Cui Chunping , Tan Sha , Tao Li , Gong Junli , Chang Yanyu , Wang Yuge , Fan Ping , He Dan , Ruan Yiwen , Qiu Wei 
Published: April 2020

Abstract
Background and purpose
The mechanism underlying the pathology of neuromyelitis optica spectrum disorder (NMOSD) remains unclear even though increased expression of the water channel protein aquaporin-4 (AQP4) on astrocytes plays an important role. Our previous study revealed that dysbiosis was detected in the faecal microbiota of NMOSD patients. In this study, we further investigated whether the intestinal barrier and mucosal flora balance were also interrupted in NMOSD patients.
Methods
Sigmoid mucosal biopsies were collected via endoscopy from six patients with NMOSD and compared with those from three patients with multiple sclerosis (MS) and five healthy controls (HCs). These samples were processed for electron microscopy and immunohistochemistry to investigate changes in ultrastructure and in the number and size of intestinal inflammatory cells. Changes in mucosal flora were also analysed by high-throughput 16S ribosomal RNA gene amplicon sequencing.
Results
The intercellular space between epithelia of the colonic mucosa became wider in MS and NMOSD patients compared to the HCs (P < 0.01), and the expression of tight junction proteins in MS and NMOSD patients significantly decreased compared to that in the HCs. Activation of microphages with many inclusions inside the cytoplasm and enlarged plasmocytes with more particles were found in the NMOSD group. Quantitative analysis showed that the percentage of small-size CD 38 + and CD138 + cells was lower but that of larger-size cells became higher in NMOSD patients, and 16S data showed that the abundance of Streptococcus and Granulicatella was dramatically increased in NMOSD patients.
Conclusions
NMOSD patients exhibited a disrupted intestinal barrier and intestinal dysbiosis and activation of intestinal inflammation, which suggested a potential pathophysiological mechanism of NMOSD underlying intestinal inflammation.
Differentially expressed circRNA and mRNA profiles of neural stem cells with radiation irradiation
Authors: Cai Zhaopeng , Wang Shan , Xie Zhongyu , Wang Peng , Shen Huiyong , Chen Keng 
Published: April 2020

Abstract
Background Spine metastasis is common but highly problematic in clinical oncology practice. Radiotherapy plays an important role in the treatment of spine metastasis, but it at the same time damages the nervous tissue, especially the neural stem cell (NSC), and leads to radiation induced myelopathy. Circular RNA (circRNA) is a kind of non-coding RNA which responses to external stimulus and regulates cellular functions. However, the mechanism of radiotherapy affecting NSC and the role of circRNA in this process are still unclear. Methods The circRNA and mRNA of NSC treated with radiation or not were detect using next-generation sequencing. RT-PCR assays were preformed to confirm the sequencing results and the feature of differentially expressed circRNA. Bioinformation analyses were conducted to identified the critical circRNA and mRNA, as well as the enriched functions and pathways. Moreover, a circRNA-miRNA-mRNA network was constructed to investigate the possible regulatory mechanism. Results A total of 421 differentially expressed circRNA and 1602 differentially expressed mRNA of NSC were identified after radiotherapy. The GO and KEGG analysis of the differentially expressed mRNA as well as the host genes of the differentially expressed circRNA were performed and several key signal pathways such as MAPK signal pathway were identified. Moreover, a circRNA-miRNA-mRNA network focusing on MAPK signal pathway was shown and predicted that chr5:127160496|127165240 could be the critical circRNA in the regulatory mechanism of radiation treated NSCs. Conclusion Our finding showed the differentially expressed circRNA and mRNA profiles of NSC after radiotherapy, suggesting that circRNA may contribute to the pathogenesis of radiation induced myelopathy.
The Value of p16INK4a Immunostaining for High-grade Squamous Intraepithelial Lesions in Human Papillomavirus–Negative Patients
Authors: Zhang Dai , Song Jie , Zhang Xiaosong , Bi Hui 
Published: April 2020

Abstract
Objective This study aims to evaluate the value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China.Methods In this study, we evaluated the value of p16INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients.Results Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16INK4a immunostaining was 0.327, 0.323, and 0.926, respectively.Conclusion Positive p16INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL + diagnosis of HPV-negative patients.
A new diagnostic work-up for defining anemia etiologies: a cohort study in general practices
Authors: Schop Annemarie , Stouten K. , Riedl J.A. , Houten R.J. van , Leening M.J.G. , Rosmalen J. van , Bindels P.J.E. , Levin M-D. 
Published: April 2020

Abstract
Purpose.
To study etiologies of anemia using an extensive laboratory analysis in general practices.
Method.
An extensive laboratory analysis was performed in blood of newly diagnosed anemia patients aged ≥ 50 years from the general population in the city of Dordrecht area, the Netherlands. Eight laboratory-orientated etiologies of anemia were defined. Patients were assigned one or more of these etiologies on the basis of their test results.
Results.
Blood of 4152 patients (median age 75 years; 49% male) was analyzed. The anemia etiology was unclear in 20%; a single etiology was established in 59%; and multiple etiologies in 22% of the patients. The most common etiologies were anemia of chronic disease (ACD) (54.5%), iron deficiency anemia (IDA) (19.1%) and renal anemia (13.8%). The most common single etiologies were IDA (82%) and ACD (68%), while the multiple etiologies most commonly included folic acid deficiency (94%) and suspected bone marrow disease (88%). Older age was associated with a lower incidence of IDA and a higher incidence of renal anemia. Mild anemia was more often associated with ACD and uncertain anemia, while severe anemia was mainly seen in patients with IDA.
Conclusion.
Extensive laboratory analysis in anemic patients from the general population helped clarify the etiology of anemia and revealed many various combinations of etiologies in a significant proportion of patients. Age, sex and the severity of anemia are predictive of the underlying etiology.
Validation of the Arabic Version of the Perinatal Anxiety Screening Scale (PASS) among Antenatal and Postnatal Women
Authors: Jr Hoda , Alfarhan Thikrayat 
Published: April 2020

Abstract
BackgroundAnxiety among women in the perinatal period is common. Assessing the severity of perinatal anxiety will help monitor the progress of the patient through the stages of anxiety and facilitated the treatment. This study assesses the validity and reliability of the “Perinatal Anxiety Screening Scale” (PASS) in the Arabic language.MethodsThe PASS was translated into Arabic. 217 women in the antenatal and postnatal phase participated (92 antenatal and 125 postnatal) answered to PASS, GHQ12, and EPDS. Content validity, factor analysis, internal consistency, and test retest reliability were assessed.ResultsContent Validity Index (CVI) and Content Validity Ratio (CVR) were .88 and 0.79; respectively. The scale loaded on four components: acute anxiety, social anxiety, and dissociation; specific fears and trauma; general anxiety and adjustment; and perfectionism and control. Cronbach’s Alpha value for the scale was 0.78 and test retest correlation coefficient was 0.94. PASS significantly correlated with EPDS (rho = 0.46) and GHQ12(rho = 0.58).ConclusionThe Arabic translated version of the PASS showed reasonably adequate validity and reliability and can be used to screen for anxiety disorder among women in the perinatal phase.
The plasma levels of mCRP is linked to cardiovascular disease in antineutrophil cytoplasmic antibody -associated vasculitis
Authors: Wu Kaili , Liang Qinghui , Ding Na , Li Bowei , Hao Jian 
Published: April 2020

Abstract
Background C-reactive protein (CRP) has 2 natural isomers, C-reactive protein pentamer (pCRP) and C-reactive protein monomer (mCRP). The levels of CRP are significantly elevated in patients with anti-neutrophil cytoplasmic antibody（ANCA)-associated vasculitis (AAV). mCRP not only can cause the activation of endothelial cells, platelets, leukocytes, and complements, but also have a proinflammatory structural subtype that can localise and deposit in inflammatory tissues, so it is an important mediator of a variety of clinical diseases, such as Ischemia/Reis perfusion (I/R) injury, Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. Complications of myocardial infarction occurred（n=4) in 37 AAV patients we collected, so it is speculated that mCRP may be related to cardiovascular disease in patients. Methods Brain natriuretic peptide (BNP) and mCRP in plasma were tested by enzyme-linked immunosorbent assay (ELISA). The Acute ST-segment elevation myocardial infarction（STEMI) diagnosed by Coronary angiography and then calculated the Gensini score. Echocardiography: ejection fraction （EF%)，left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular mass index (LVMI). Glomerular filtration rate (eGFR) was calculated based on serum creatinine, age, and gender. Results The plasma levels of mCRP in AAV was significantly higher than that in healthy volunteers (P<0.001). There were 4 STEMI complications in AAV. We compared mCRP and CRP levels with STEMI complication and without STEMI complications in AAV, the plasma levels of mCRP was higher, however the plasma levels of CRP was lower in STEMI. Plasma levels of mCRP correlated with Birmingham vasculitis activity score (BVAS), eGFR, BNP, EF%, LVEDV, LVESV, LVMI ( r =0.404, P =0.013; r =-0.341, P =0.039; r =0.349, P =0.034; r =-0.362, P =0.027; r =0.375, P =0.022; r =0.334, P =0.043; r =0.736, P <0.001) and STEMI complications’ Gensini score (r=0.977, P=0.023) in AAV, however CRP didn’t correlate with BNP, EF%, LVEDV, LVESV, LVMI and Gensini score. Conclusions The plasma levels of mCRP related to cardiovascular diseases in AAV patients.