bluuebunny/crossref_metadata_2025 huggingface dataset:
The changing states of fibromyalgia in patients with axial spondyloarthritis: results from the British Society of Rheumatology Biologics Register for Ankylosing Spondylitis
Authors: Provan Sella A , Dean Linda E , Jones Gareth T , Macfarlane Gary J
Published: December 2020

Objectives

To identify factors associated with FM development and recovery in patients with axial SpA (axSpA).

Methods

The British Society of Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited patients with axSpA from 83 centres in a prospective study. FM was diagnosed using the self-reported Fibromyalgia Survey Diagnostic Criteria from 2015. Measures of axSpA disease activity and clinical findings were recorded at regular intervals. We identified predictors for FM development and recovery between yearly visits using uni- and multivariable logistic regression models.

Results

A total of 801 participants, 247 (30.8%) female, had two or more visits and were eligible for inclusion. A total of 686 participants did not have FM at baseline, of whom 45 had developed FM at follow-up, while 115 participants had FM at baseline, of whom 77 had recovered at follow-up. A high baseline BASDAI score [odds ratio (OR) 1.27 (95% CI 1.08, 1.49)] and Widespread Pain Index (WPI) [OR 1.14 (95% CI 1.02, 1.28)] were significantly associated with FM development in the final multivariable model. A low baseline BASFI score [OR 0.68 (95% CI 0.53, 0.86)] and WPI [OR 0.84 (95% CI 0.720, 0.97)] and starting a TNF inhibitor [OR 3.86 (95% CI 1.54, 9.71)] were significantly associated with FM recovery.

Conclusion

High levels of disease activity and the presence of widespread pain is associated with the development of FM in patients with axSpA, while low levels of the same variables and starting a TNF inhibitor are associated with recovery from FM. The presence of comorbid FM should be considered in patients with persistent high axSpA disease activity and widespread pain.
Impact of aging on phenotype and prognosis in IgA vasculitis
Authors: Audemard-Verger Alexandra , Pillebout Evangéline , Baldolli Aurélie , Gouellec Noémie Le , Augusto Jean-François , Jourde-Chiche Noémie , Raffray Loic , Thervet Eric , Deroux Alban , Goutte Julie , Hummel Aurélie , Lioger Bertrand , Sanges Sébastien , Cacoub Patrice , Amoura Zahir , Moulis Guillaume , Maurier Francois , Lavigne Christian , Urbanski Geoffrey , Chanal Johan , Faguer Stanislas , Deriaz Sophie , Feirreira-Maldent Nicole , Diot Elisabeth , Maillot Francois , Guillevin Loïc , Terrier Benjamin
Published: December 2020

Objectives

Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV.

Methods

We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset.

Results

Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age.

Conclusion

Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
Civil Liability Institution in Ukraine through the Lens of Reform and European Integration Processes
Authors: Kuznietsova Nataliia S , Kot Oleksii O , Khomenko Mykhailo M
Published: December 2020

Modern aspirations of Ukraine for European integration, the impact of globalization, and innovative technologies are the driving force on the path of reforming the national legal system. In this regard, issues concerning the modernization of the civil liability have recently become of significant importance. This article is aimed at analysing modernization of Ukrainian civil liability and forecasting tendencies of further reform of the civil liability institution in Ukraine. The methodological basis of the article includes the comparative law method, normative-dogmatic method, method of terminological analysis, method of operationalization of concepts, classification method, methods of analysis and synthesis, statistical method, legal modelling method, and complex method. In the course of the research-leading scientific and legal approaches to civil liability were analysed, and the most typical approaches were unified. A conditional list of the leading directions of modernization of legal regulation of the civil liability institution is proposed. The relevance of the subject matter is amplified by the fact that at present the scope of the most important and reforming issues of civil liability is expanding and remains either understudied or entirely disregarded by the representatives of academia and legislators.
Origin of Life
Authors: Deamer David W.
Published: December 2020

Our knowledge of our solar system has passed the point of no return. Increasingly, it seems possible that scientists will soon discover how life is created on habitable planets like Earth and Mars. Scientists have responded to a renewed public interest in the origin of life with research, but many questions still remain unanswered in the broader conversation. Other questions can be answered by the laws of chemistry and physics, but questions surrounding the origin of life are best answered by reasonable extrapolations of what scientists know from observing the Earth and its solar system. Origin of Life: What Everyone Needs to Know® is a comprehensive scientific guide on the origin of life. David W. Deamer sets out to answer the top forty questions about the origin of life, including: Where do the atoms of life come from? How old is Earth? What was the Earth like before life originated? Where does water come from? How did evolution begin? After he provides the informational answer for each question, there is a follow-up: How do we know? This question expands the horizon of the whole book, and provides scientific reasoning and explanations for hypotheses surrounding the origin of life. How scientists come to their conclusions and why we can trust these answers is an important question, and Deamer provides answers to each big question surrounding the origin of life, from what it is to why we should be curious.
Mexico
Authors: Camp Roderic Ai
Published: December 2020

Today all would agree that Mexico and the United States have never been closer--that the fates of the two republics are inextricably intertwined. It has become an intimate part of life in almost every community in the United States, through immigration, imported produce, business ties, or illegal drugs. It is less a neighbor than a sibling; no matter what our differences, it is intricately a part of our existence. In the fully updated second edition of Mexico: What Everyone Needs to Know®, Roderic Ai Camp gives readers the most essential information about our sister republic to the south. Camp organizes chapters around major themes--security and violence, economic development, foreign relations, the colonial heritage, and more. He asks questions that take us beyond the headlines: Why does Mexico have so much drug violence? What was the impact of the North American Free Trade Agreement? How democratic is Mexico? Who were Benito Juárez and Pancho Villa? What is the PRI (the Institutional Revolutionary Party)? The answers are sometimes surprising. Despite ratification of NAFTA, for example, Mexico has fallen behind Brazil and Chile in economic growth and rates of poverty. Camp explains that lack of labor flexibility, along with low levels of transparency and high levels of corruption, make Mexico less competitive than some other Latin American countries. The drug trade, of course, enhances corruption and feeds on poverty; approximately 450,000 Mexicans now work in this sector. Brisk, clear, and informed, Mexico: What Everyone Needs To Know® offers a valuable primer for anyone interested in the past, present, and future of our neighbor to the South.
Buddhism
Authors: Wright Dale S.
Published: December 2020

Buddhism is one of the oldest and largest of the world’s religions. But it is also a tradition that has proven to have enormous contemporary relevance. Founded by Siddhartha Gautama, who came to be called the Buddha, the religion has spread from its origins in northeast India, across Asia, and eventually to the West, taking on new forms at each step of the way. Buddhism: What Everyone Needs to Know offers readers a brief, authoritative guide to one of the world’s most diverse religious traditions in a reader-friendly question-and-answer format. Dale Wright covers the origins and early history of Buddhism, the diversity of types of Buddhism throughout history, and the status of contemporary Buddhism. This is a go-to book for anyone seeking a basic understanding of the origins, history, teachings, and practices of Buddhism.
Adherence to gout guidelines: where do we stand?
Authors: Ho Gary H. , Pillinger Michael H. , Toprover Michael
Published: December 2020

Purpose of review

Although gout is a common, well-recognized, and extensively researched rheumatologic disease, it continues to be underappreciated and undertreated. Although the prevalence of gout has been rising over the past several decades, adherence to urate lowering therapy continues to be suboptimal. Recent studies have underscored the potential success of guideline-directed therapy.

Recent findings

Adherence to gout treatment continues to be suboptimal according to multinational metaanalyses. Moreover, studies measuring adherence are prone to overestimation and each methodologic approach has intrinsic limitations. Adherence may be analyzed from the perspective of patient adherence to taking a medication, or provider adherence to treatment guidelines. In addition to considering traditional risk factors, adherence should be viewed through the lens of healthcare disparities. The RAmP-Up trial and Nottingham Gout Treatment trial demonstrate the success of protocolized gout treatment using existing guidelines for reference.

Standardized gout treatment protocols should be established for all primary care and specialty practices. Two successful methods of improving adherence include using nonphysician providers to coordinate urate lowering therapy titration and monitoring serum urate. Having more frequent outpatient visits to focus on direct patient care and education has also been successful.
Mediating effect of social support on the association between life events and depression
Authors: Liu Liang , Liu Chaojie , Ke Xiong , Li Ningxiu
Published: December 2020

Depression is one of the most common mental health problems in adolescents. The link between negative life events and depression has been well established. However, our understanding about the role of social support in the link, which is likely culture-dependent, is quite limited. This study aimed to determine the mediating effect of social support on the association between life events and depression in adolescents in Chongqing China.

A total of 1512 adolescents aged 12 to 17 years old in Chongqing of China were selected using a stratified cluster sampling strategy. Depression symptoms, negative life events, and perceived social support of the participants were measured using the Children's Depression Inventory, Adolescent Life Event Scale, and Child and Adolescent Social Support Scale, respectively. Pearson correlation analyses were performed to detect their associations. A multivariate linear regression model was established to determine the association between life events and depression after adjustment for variations in socio-demographic variables. The mediating effect of social support on the association between negative life events and depression was tested using the structural equation model.

About 16.8% of the participants were detected with depression. Depression was associated with negative life events and low levels of social support (P < .05). Both frequency and perceived importance of social support showed a mediating effect on the association between life events and depression.

Social support has a mediating effect on the association between life events and depression. Strengthening social support may be considered as an effective interventional strategy on depression in adolescents.
Comparison of empirical high-dose and low-dose of meropenem in critically ill patients with sepsis and septic shock
Authors: Ye Xiaolin , Wang Fei , Zeng Wenqing , Ding Yueping , Lv Bin
Published: December 2020

Background:

Sepsis and septic shock syndrome are the main problems in modern medicine. Current treatment guidelines for the sepsis recommend an appropriate and timely antibiotic treatment. Meropenem has activity against a wide variety of Gramnegative and Gram-positive bacteria. At present, there are few studies on the application of high-does meropenem in the patients with sepsis and septic shock. We therefore carry out the randomized controlled research to compare the low-dose and high-dose meropenem in the critically ill sepsis and septic shock patients, and to assess the safety of the two regimens.

Method:

This is a prospective, single-center, and randomized research authorized through the local research ethics committee of Zhejiang Chinese Medical University (No.32198276). Sixty-four participants with a diagnosis of sepsis and septic shock are analyzed. Patients who meet the following conditions will be included:

Patients with the following conditions will be excluded

They are assigned to 2 groups, namely, the standard-does group and high-dose group, in the standard-does group, they receive low-dose meropenem (intravenous injection of 1 g meropenem for more than 30 minutes, followed by intravenous injection of 1 g meropenem for more than three hours every 8 hours), and in the high-dose group, patients receive high-does meropenem (intravenous injection of 2 g meropenem for more than 30 minutes, and then intravenous injection of 2 grams of meropenem for more than three hours every 8 hours). The main outcomes are the modified Acute Physiology and Chronic Health Evaluation II (APACHE II) and scores of Sequential Organ Failure Assessment (SOFA). And the secondary outcomes are the 14-day mortality and 28-day mortality, the rate of microbiological cure and clinical cure, ventilator-free days, vasopressor-free days, hospital-free days and the ICU-free days, as well as safety in the two regimen groups. All analysis in our work is carried out via utilizing the software of IBM SPSS Statistics for Windows, version 20.

Results:

Figure 1 reveal the primary outcomes and the secondary outcomes.

Conclusion:

This protocol can provide a reliable evidence for the safety and effectiveness of the high-dose meropenem in the critically ill sepsis and septic shock patients.

Trial registration number:

researchregistry6023
Effectiveness and safety of different medicines for Uremia pruritus
Authors: Yan Shifan , Yu Ting , Li Fusheng , Huang Yong , Xiao Lu , Li Haiqun , Wang Maohong
Published: December 2020

Introduction:

A large number of patients will experience pruritus after uremia. Medicine is the preferred treatment for many doctors, but the effectiveness and safety of different medicines for uremia pruritus has not yet been comprehensively compared, based on network meta-analysis.

Methods and analysis:

According to the retrieval strategy, two team members independently searched the literature in 7 databases, and imported the retrieval results into the EndNote Software AQ8 (V.X9). After deleting repeated articles, they read the abstract and the full text, selected the articles that met the inclusion criteria and extracted valid information. The main results were visual analogue scale (VAS) and the secondary results were verbal rating scale (VRS), Dirk R Kuypers score, and adverse event incidence. The methodological quality evaluation was conducted from 7 aspects, according to The Cochrane Collaborative Tool, Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) was used for data analysis. The level of evidence will be assessed by the Grading of Recommendations, Development and Evaluation (GRADE) instrument).

Results:

The results will rank the efficacy of drugs used to treat uremic pruritus and assess their safety.

Conclusion:

This study is the first to compare the efficacy and safety of medicines for uremic pruritus based on network analysis and will provide evidence and ideas for the treatment of uremic pruritus.

INPLASY registration number:

No. INPLASY202090103.
The efficacy of Chinese herbal medicine as an adjunctive therapy for colorectal cancer
Authors: Li Wenyuan , Guo Jing , Wang Qiaoling , Tang Jianyuan , You Fengming
Published: December 2020

Background:

Colorectal cancer (CRC) is a public health problem and the world's leading cancer killer. It is a disease with high incidence and mortality. Although chemotherapy has achieved some success in the treatment of CRC, drug resistance and tumor metastasis caused by chemotherapy are still the main causes of death in patients with CRC. Notably, many side effects associated with chemotherapy, such as nausea, vomiting, and peripheral neurotoxicity, are major challenges in the treatment of patients with CRC. Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for CRC, but its efficacy and safety are still uncertain. The aim of this systematic review is to assess the efficacy and safety of CHM for the treatment of CRC.

Methods:

A comprehensive retrieval will be performed in the following electronic databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, SinoMed, VIP, and Wan Fang Data. The methodologic quality of randomized controlled trials will be assessed using the Cochrane risk assessment tool. Review Manager 5.3 software will be used for data synthesis and analysis. Funnel plot analysis and Egger test will be used to assess publication bias. The Grading of Recommendations Assessment, Development and Evaluation standard will be used to generate summary of finding table.

Results:

The results of this systematic review will be used to summarize and evaluate the evidence from randomized controlled clinical trials of CHM as adjuvant therapy for CRC.

Conclusion:

This review will provide a detailed summary of the evidence to assess the efficacy and safety of CHM for CRC.

OSF Registration:

DOI 10.17605/OSF.IO/X2SKJ
Acupoint injection treatment for non-dialysis dependent chronic kidney disease
Authors: Yang Tiantian , Zhao Junnan , Guo Qi , Wang Yanfang , Si Guomin
Published: December 2020

Aim:

To analyze the effects of acupoint injection in the treatment of non-dialysis dependent chronic kidney disease through a systematic review with meta-analysis.

Methods:

This systematic review with meta-analysis was conducted following the recommendations of the declaration of PRISMA. Full-text literature of randomized controlled trial of acupoint injection therapy for non-dialysis chronic kidney disease was searched in PubMed, Embase, Cochrane Library, China National Knowledge Internet, the Chinese Scientific Journal Database, the Wanfang Database, China Biology Medicine database. The efficacy and safety of acupoint injection for non-dialysis chronic kidney disease were evaluated.

Results:

Seventeen studies containing 1414 patients met the criteria. The results shows that acupoint injection combined with basic treatment can significantly improve the levels of Ccr (WMD = 4.81; 95% CI:2.54 to 7.08) and Hb (WMD = 4.56; 95% CI:1.72 to 7.39), reduce the levels of BUN (WMD = −0.90; 95% CI: −1.26 to −0.54)and Scr (WMD = −7.66; 95% CI: −12.39 to −2.93), and improve the effective rate (OR = 3.12; 95% CI: 2.29 to 4.26).

Conclusion:

Our current analysis showed that combined acupoint injection therapy can reduce the levels of BUN and Scr, and increase Ccr and Hb in non-dialysis CKD patients. However, the existing evidence is still insufficient due to the high risk of included trial bias, and future research needs to improve methodological quality.

Registration number: CRD42020168143.
The risk factors for the postoperative pulmonary infection in patients with hypertensive cerebral hemorrhage
Authors: Xu Shihai , Du Bo , Shan Aijun , Shi Fei , Wang Jin , Xie Manying
Published: December 2020

The risk factors for the pulmonary infections after hypertensive cerebral hemorrhage remains unclear. We aimed to investigate the potential risk factors for the postoperative pulmonary infection in patients with hypertensive cerebral hemorrhage.

Patients with hypertensive cerebral hemorrhage undergone surgery from January 2018 to December 2019 were included. Related personal and medical information were collected. Univariate and multivariate logistic regression analyses were performed to identify the potential risk factors for the postoperative pulmonary infection.

A total of 264 patients were included, and the incidence of pulmonary infection for patients with hypertensive cerebral hemorrhage after surgery was 19.70%. Escherichia coli is the most common bacteria of pulmonary infection. Multivariate regression analysis revealed that the preoperative hypoalbuminemia (OR2.89, 1.67∼4.78), tracheotomy (OR5.31, 1.24∼11.79), diabetes (OR4.92, 1.32∼9.80), preoperative GCS (OR5.66, 2.84∼11.21), and the duration of mechanical ventilation (OR2.78, 2.32∼3.61) were the independent risk factors for the pulmonary infection in patients with hypertensive cerebral hemorrhage (all P < .05).

Patients with hypertensive intracerebral hemorrhage after surgery have a higher risk of postoperative pulmonary infections, and there are many related risk factors, which should be taken seriously in clinical practice.
Identification of biomarkers associated with diagnosis and prognosis of gastroesophageal junction adenocarcinoma–a study based on integrated bioinformatics analysis in GEO and TCGA database
Authors: Song Danlei , Tian Jiming , Hu Yuping , Wei Yongjian , Lu Hong , Wang Yuping , Guan Quanlin , Zhou Yongning
Published: December 2020

Gastroesophageal junction adenocarcinoma (GEJAC) is a malignant tumor with high mortality. Its incidence has increased sharply all over the world in recent years. The study aims to search for potential biomarkers for the diagnosis and prognosis of GEJAC based on the Gene Expression Omnibus database (GEO) database and The Cancer Genome Atlas (TCGA) database.

Microarray dataset (GSE96668 and GSE74553) of GEJAC was downloaded from the GEO. After screening overlapping differentially expressed genes (DEGs) by GEO2R and Wayne map, functional enrichment analysis of the DEGs was performed by the DAVID database. Then, a protein–protein interaction (PPI) network was constructed, and the hub gene was identified by using STRING and Cytoscape, as well as the diagnostic value of hub genes was evaluated by the receiver operating characteristic (ROC) curves. Finally, the gene transcriptome profiles of gastric cancer named TCGA-STAD were downloaded from TCGA database to screen the potential prognostic genes and construct the prognostic risk model using Cox proportional hazards regression. Meanwhile, the Kaplan–Meier curve and time-dependent ROC curve were adopted to test the prognostic value of the prognostic gene signature.

In this study, we identified 10 hub genes that might have high diagnostic value for GEJAC, and inferred that they might be involved in the occurrence and development of GEJAC. Moreover, we conducted a survival prediction model consisting of 6 genes and proved that they have value to some extent in predicting prognosis for GEJAC patients.
Tumor lysis syndrome in chronic lymphocytic leukemia: conventional treatment versus novel agents
Authors: Kassem Nancy , Ghazy Ahmed A. , Abu-Tineh Mohammad , Omar Nabil E. , Nashwan Abdulqadir J. , Chandra Prem , Ghasoub Rola , AbuTabar Osama S. , Yassin Mohamed A.
Published: December 2020

Introduction:

Existing evidence on the difference in the incidence of tumor lysis syndrome (TLS) in Chronic Lymphocytic Leukemia (CLL) patients receiving novel therapies versus patients receiving conventional therapies is limited and inconclusive. The aims of this planned systematic review and meta-analysis are therefore

Methods:

We will conduct a systematic review and meta-analysis. Several electronic databases will be searched using predefined search terms to identify relevant studies. Eligible studies should report findings on the incidence of TLS in CLL patients. Primary observational studies with cross-sectional or prospective research design, case-control studies, and studies with experimental designs will be included. Study quality will be evaluated by 2 reviewers using the statistical methodology and categories described in the Cochrane Collaboration Handbook and preferred reporting items for systematic reviews and meta-analyses and other applicable guidelines. The meta-analysis will be performed and conducted using applicable standard statistical software like comprehensive meta-analysis and STATA.

Discussion:

This review and meta-analysis will be among the first to systematically explore and integrate the evidence available on the comparison between the incidences of TLS in CLL patients treated with novel agents versus conventional agents. By gathering and summarizing information about the risk of TLS in this patient population, the findings from this review will provide insights for future research directions and more understanding of the difference of TLS incidence between novel treatments and conventional treatment and suggest prophylactic measures for such cases.

Systematic review registration:

The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020166770).

The protocol was registered with the Hamad medical corporation, Medical research Center registry under a unique reference number (MRC-01-20-709).
Comparison of Whitacre needle and Chiba needle on the incidence of intravascular injection during caudal epidural injections
Authors: Lee Jungwon , Kim Saeyoung , Park Sungsik , Kim Sioh , Youn Si-Jeong , Jeon Younghoon
Published: December 2020

Caudal epidural injection (CEI) is effective for lumbar spinal pain. However, accidental intravascular injection reduces therapeutic efficacy of CEI and leads to fatal complications such as hematoma, and neurologic deficit. Whitacre needle has been reported to be effective for reducing intravascular injection during transforaminal epidural injection, compared with Quincke needle. The bevel of Chiba needle is shorter than that of Quincke needle. In this study we compared Whitacre needle and Chiba needle on incidence of intravascular injection during CEI.

This was a single-blind, randomized clinical consort study. After institutional Review Board approval, a total of 164 patients underwent CEI were randomly allocated to one of 2 group (Whitacre needle or Chiba needle group). Intravascular injection was assessed with real-time fluoroscopy. In addition, total procedure time was measured. Data were compared between groups, and P < .05 was consideredstatistically significant.

There were no differences between groups in terms of patient demographic and clinical characteristics. There was no significant difference on incidence of intravascular injection between Whitacre and Chiba needle group (11% vs 19.5%, P = .192). However, the procedure time is significantly longer in the Whitacre than Chiba needle group (172.8 ± 53.8 sec vs 147.1 ± 61.1 sec, P = .005).

Based on current study, our results indicated that Whitacre needle was not effective to decrease the incidence of intravascular injection during CEI, compared to Chiba needle.
The incidence and prognostic effect of Fms-like tyrosine kinase 3 gene internal tandem and nucleolar phosphoprotein 1 genes in acute myeloid leukaemia
Authors: Liu Heping , Zhang Xiaolian , Li Ming , Zhou Wei , Jiang Guangrong , Yin Weihua , Song Chunping
Published: December 2020

Background:

Molecular genotyping is an important prognostic role in acute myeloid leukemia (AML) patients. We aimed to design this meta-analysis to discuss the incidence and prognostic effect of nucleolar phosphoprotein 1 (NPM1) and Fms-like tyrosine kinase 3 gene internal tandem (FLT3-ITD) gene in AML patients.

Methods:

PubMed, Embase, Medline, and Cochrane library were systematically searched due to May 15, 2020. Four combinations of genotypes (FLT3-ITDneg/NPM1mut, FLT3-ITDpos/NPM1mut, FLT3-ITDneg/NPM1wt, FLT3-ITDpos/NPM1wt) were compared in association with the overall survival (OS) and leukemia-free survival (LFS) outcome, which expressed as pooled hazard ratio (HR) and 95% confidence intervals (CIs).

Results:

Twenty-eight studies were included in our study. The incidence of FLT3-ITDneg/NPM1mut, FLT3-ITDpos/NPM1mut, FLT3-ITDneg/NPM1wt, and FLT3-ITDpos/NPM1wt was 16%, 13%, 50%, and 10%, respectively. The patients with FLT3-ITDneg/NPM1mut gene may have the best OS and LFS when comparing with FLT3-ITDpos/NPM1mut (HR = 1.94 and 1.70, P < .01), FLT3-ITDneg/NPM1wt (HR = 1.57 and 2.09, P < .01), and FLT3-ITDpos/NPM1wt (HR = 2.25 and 2.84, P < .001).

Conclusion:

AML patients with FLT3-ITDneg/NPM1mut gene type have the best survival outcome than the other 3 gene types, which should be an independent genotyping in AML classification.
Coronavirus disease 2019 pandemic stress and its effects on irritable bowel syndrome patients in Saudi Arabia
Authors: Alzahrani Mohammed A. , Alshamrani Ali S. , Ahmasani Ibrahim M. , Alahmari Fahad S. , Asiri Ali H. , Alshehri Abdullah M. , Alsamghan Awad S. , Awadalla Nabil J.
Published: December 2020

Coronavirus disease 2019 (COVID-19 pandemic has affected the psychological health of people, causing a higher level of stress. Stress can exaggerate the symptoms of irritable bowel syndrome (IBS).

To assess the effect of the COVID-19 pandemic stress on patients with IBS in Saudi Arabia.

A descriptive cross-sectional approach was used, which targeted accessible subjects with IBS from different regions of Saudi Arabia. Data were collected from participants using a structured electronic questionnaire, which captured the participants’ socio-demographic data, medical history, IBS clinical data, self-reported stress due to COVID-19, and its effect on IBS symptoms.

A total of 1255 IBS patients completed the questionnaire. About 63.4% of them reported stress due to the pandemic. The most frequently reported causes of stress were fear of infection occurring in the family, followed by fear of self-infection (43.5%), and death due to COVID-19 infection (17.2%). Most of the stressed participants (56.6%) reported that stress usually exaggerated IBS symptoms. Almost 22% of them consulted a physician for stress aggravation of the symptoms, 18.1% used sedatives due to stress, 9.2% modified IBS medications due to the stress, and 75.5% of the participants reported impaired daily activities due to symptoms exacerbation. Coexisting chronic morbidities and inability to differentiate between COVID-19 gastrointestinal symptoms and IBS symptoms were significantly associated with COVID-19 related stress (P = .039 and .001, respectively).

Two-thirds of IBS patients were stressed during the first few months of COVID-19 pandemic. Patients unable to differentiate between COVID-19 gastrointestinal tract symptoms and IBS symptoms, and patients suffering from chronic morbidities were more vulnerable. Pandemic stress exacerbated patients’ symptoms and impacted their activities of daily life.
The relationship between quantitative epicardial adipose tissue based on CT and coronary artery disease
Authors: Wu Baohua , Ren Zhuanqin , Du Zhengang , Zhang Lei , Hou Bin
Published: December 2020

Background:

Epicardial adipose tissue (EAT) is a kind of visceral adipose tissue with close proximity to coronary artery and myocardium, which can secrete cell factor, and influence the physiological function and pathophysiological process of myocardium and coronary artery. Clinical imaging diagnosis showed that the volume and thickness of EAT exists a certain relevance with coronary artery disease, but it lacked evidence of evidence-based medicine. The research on the implementation of this program will systematically evaluate the relationship of computed tomography (CT) quantitative EAT and coronary artery disease.

Method:

The English databases (Embase, PubMed, the Cochrane Library, Web of Science) and Chinese database (CNKI, Wanfang, China biomedical database, VIP) of computer retrieval has collected the case control clinical study of relationship between EAT and coronary artery disease from the establishment of the database to October 2020, which was conducted extraction and quality evaluation by 2 researchers independently for data included in the study, and was conducted Meta-analysis for the included literature by adopting RevMan5.3 software.

Result:

The research evaluated the correlation between EAT and coronary artery disease through the EAT thickness, EAT volume, and other indexes.

Conclusion:

The research has provided reliable evidence-based evidence for the correlation between CT EAT quantification and coronary artery disease.

Ethics and dissemination:

We will not publish private information from individuals. This kind of systematic review does not involve harming the rights of participants. No ethical approval was required. The results can be published in peer-reviewed journals or at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/DVQNE
A prospective randomized controlled clinical trial of Pingmu Decoction combined with acupuncture in the treatment of non-active thyroid-related ophthalmopathy
Authors: Li Hongyan , Zheng Pengfei , Min Jie , Zhang Yali , Wang Wei , Zhang Jingwen , Li Hong
Published: December 2020

Background:

Thyroid eye disease of orbital disease first, it is main and clinical expression with exophthalmos, visual impairment, serious influence patient's quality of life and beautiful, especially for the non-active Graves’ ophthalmopathy, there is no effective treatment methods at home and abroad, for the non-active thyroid eye disease only recommended surgery, but the procedure pain, poor curative effect, postoperative recurrence, most patients are difficult to accept. Pingmu Decoction can effectively reduce the degree of exophthalmus and TCM syndrome integral, and The combination therapy with acupuncture and moxibustion on the basis of Pingmu Decoction has achieved remarkable clinical effect, but the lack of rigorous evidence of evidence-based medicine (ebm). The test is designed to further evaluate flat mesh in active soup combined with acupuncture treatment of thyroid related ophthalmopathy card belongs to the yang qi-deficiency, phlegm and blood stasis block syndrome in patients with clinical efficacy and safety.

Methods/Design:

A prospective, randomized controlled clinical trial will be conducted to evaluate the efficacy and safety of Pingmu Decoction combined with acupuncture in the treatment of non-active thyroid-related eye disease in patients with Yang qi deficiency and phlegm-blood stasis syndrome. A total of 120 patients with non-active thyroid-related eye disease, namely deficiency of Yang qi and blockage of phlegm and blood stasis, are randomly divided into 3 groups and treated for 12 weeks. All three groups will maintain basic western medicine treatment. The primary outcomes are to observe the degree of prominence of eyes, and the TCM syndrome scores. The secondary result is clinical efficacy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb)will be used as the observation indicators in this study. In addition, adverse reactions will be observed and recorded as safety indicators.

Discussion:

The results of this trial will provide convincing evidence for the efficacy and safety of Pingmu Decoction combined with acupuncture in the treatment of patients with non-active thyroid-associated eye disease with deficiency of Yang qi and phlegm and blood stasis block, and it will expand the treatment options for patients with non-active thyroid-related eye disease.

Trial registration:

Clinical Trials.gov ID: ChiCTR2000039626. Registered on 3 November 2020.
The clinical efficacy of acupoint sticking combined with massage to treatment functional dyspepsia
Authors: Wu Xiaoyan , Jiang Weijun , Shi Chunxiang , Qian Hui , Fan Xinguo , Zhou Ping
Published: December 2020

Background:

The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of acupoint sticking combined with massage (ASM) in the treatment of functional dyspepsia (FD), and provide clinicians with evidence on which to base their clinical decision making.

Methods:

This review will include all studies comparing clinical efficacy of ASM in the treatment of FD. The search strategy will be performed in 10 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is alleviation of global dyspeptic symptoms, alleviation of individual dyspeptic symptoms, quality-of-life improvement, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software.

Results:

This study will summarize current evidence to assess the efficacy and safety of ASM in the treatment of FD.

Conclusion:

The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of ASM.

Registration number:

INPLASY2020110072 (DOI number: 10.37766/inplasy2020.11.0072).
Application of a real-time cell analysis system in the process development and quantification of Rift Valley fever virus clone 13
Authors: Moetlhoa Boitumelo , Naicker Leeann , Hayeshi Rose , Grobler Anne , Mokoena Nobalanda B. , Mawadza Crispen
Published: December 2020

Conventional cell-culture viral quantification methods, namely viral plaque and 50 % tissue culture infective dose assays, are time-consuming, subjective and are not suitable for routine testing. The viral plaque formation assay is the main method utilized for Rift Valley fever virus (RVFV) clone 13 quantification. The RVFV is a mosquito-borne RNA Phlebovirus belonging to the family Bunyaviridae. The virus comprises a single serotype and causes the zoonotic Rift Valley fever disease. The real-time cell analysis (RTCA) system has been developed for the monitoring of cell growth, cell adhesion, cell viability and mortality using electronic impedance technology. In this study, Vero cell growth kinetics and RVFV clone 13 replication kinetics were investigated in a roller bottle and RTCA systems. In roller bottles, Vero cell growth was measured by cell counts through trypan blue staining, whilst impedance expressed as the cell index (CI) was used for Vero growth measurement in the RTCA system. Similar growth patterns were observed in both roller bottle and RTCA systems. Exponential growth phase was observed between 48 and 100 h, followed by a stationary phase from 100 to 120 h, before cell death was observed. Viral plaque assay quantification of RVFV clone 13 in the roller bottle system and the time required for the CI to decrease 50 % after virus infection (CIT50) in the RTCA system were comparable. The highest RVFV clone 13 titre was obtained at 120 h in both roller bottle and RTCA systems. An increase in time for cytopathic effect (CPE) formation was observed with a decrease in the concentration of the virus used to infect the RTCA plates. A positive correlation was observed between the viral concentration and the time for a CPE and was used to calculate CIT50. A similar correlation was observed between the viral concentration and the time for a CPE in the roller bottle system. This study shows that the RTCA system can be used as an alternative method for conducting cell culture kinetics and viral quantification.
Bluetongue virus serotype 12 enters Australia – a further incursion of novel western lineage genome segments
Authors: White John R. , Williams David T. , Davies Kelly , Wang Jianning , Chen Honglei , Certoma Andrea , Davis Steven S. , Weir Richard P. , Melville Lorna F. , Eagles Debbie
Published: December 2020

Bluetongue virus (BTV) is an arbovirus (genus: Orbivirus) that occurs worldwide. It infects domestic and wild ruminant species and can cause disease in livestock, producing high economic impact. Recently, it gained extra prominence throughout Europe, with disease occurring in regions traditionally free of BTV. BTV enters Australia from Southeast Asia via wind-borne infected Culicoides spp. The first Australian isolation was 1975 (BTV-20) and further serotypes were isolated between 1979–86 (BTV-1, -3, -9, -15, -16, -21, -23). Despite increased, more sensitive, monitoring, no more were detected in over two decades, implying a stable BTV episystem of eastern ancestry. Isolations of BTV-2, -7 and -5 then occurred between 2007–15, with the latter two possessing genome segments with high sequence identity to western isolates. We report on the first isolation and genomic characterization of BTV-12, which revealed that three more novel western topotype gene segments have entered northern Australia.
Human Safety, Tolerability, and Pharmacokinetics of a Novel Broad-Spectrum Oral Antiviral Compound, Molnupiravir, with Activity Against SARS-CoV-2
Authors: Painter Wendy P. , Holman Wayne , Bush Jim A. , Almazedi Firas , Malik Hamzah , Eraut Nicola C. J. E. , Morin Merribeth J. , Szewczyk Laura J. , Painter George R.
Published: December 2020

Molnupiravir, EIDD-2801/MK-4482, the prodrug of the ribonucleoside analog ß-d-N4-hydroxycytidine (NHC), has activity against a number of RNA viruses including severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, seasonal and pandemic influenza viruses, and respiratory syncytial virus.

Single and multiple doses of molnupiravir were evaluated in this first-in-human, phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, which included evaluation of the effect of food on pharmacokinetics.

EIDD-1931 appeared rapidly in plasma, with a median time of maximum observed concentration of 1.00 to 1.75 hours, and declined with a geometric half-life of approximately 1 hour, with a slower elimination phase apparent following multiple doses or higher single doses (7.1 hours at the highest dose tested). Mean maximum observed concentration and area under the concentration versus time curve increased in a dose-proportional manner, and there was no accumulation following multiple doses. When administered in a fed state, there was a decrease in the rate of absorption, but no decrease in overall exposure.

Molnupiravir was well tolerated. Fewer than half of subjects reported an adverse event, the incidence of adverse events was higher following administration of placebo, and 93.3% of adverse events were mild. One discontinued early due to rash. There were no serious adverse events and there were no clinically significant findings in clinical laboratory, vital signs, or electrocardiography. Plasma exposures exceeded expected efficacious doses based on scaling from animal models; therefore, dose escalations were discontinued before a maximum tolerated dose was reached.

Clinical trial identifier

This study was registered at ClinicalTrials.gov with the identifier NCT04392219.
Body site-specific and disease-specific virulome in the human microbiome
Authors: Liu Fei , Dong Wanting , Guo Yaqiong , Xiong Qian , Lu Na , Song Xiaofeng , Xue Yong , Cao Demin , Fan Xinyue , Fang Yuan , Li Zhiyuan , Cao Jian , Wang Yanan , Yang Guowei , Gao George F. , Zhao Fangqing , Zhu Baoli
Published: December 2020

Human body habitats are home to a diverse array of microbes, and within these microbial ecosystems, there are exchanges of genetic material, including virulence factors (VFs). Little is known about the diversity and abundance of VFs in different body sites and different types of diseases. We developed a virulome analysis pipeline using the species-specific sequence identity inferred from intraspecies ANI values to precisely assign reads to virulence factors. We characterized the human virulome from four body habitats, including the gut, oral cavity, skin, and vagina. Specifically, the diversity and abundance of VFs in the oral cavity were significantly higher than those in other body sites, including stool. We highlight the importance of sex-specific analysis when studying the human virulome. We analyzed data from more than 4,000 samples across healthy and diseased subjects and 13 types of diseases from different metagenomic sequencing studies to characterize the disease-specific virulome. Atherosclerotic cardiovascular disease (ACVD) has a more diverse virulome than other diseases tested. Notably, many VFs, including genes for secretion systems and toxins, are more abundant in diseased subjects than in healthy controls. We present, to our knowledge, the most comprehensive healthy and diseased virulome dataset yet created.
Efficacy and Safety of Indomethacin in Covid -19 patients
Authors: Ravichandran Rajan , Purna Prassana , Vijayaragavan Sivakumar , Kalavakollu Ravi Teja , Gaidhane Shilpa , Krishna Kumar Ramarathnam
Published: December 2020

Abstract
Background
Indomethacin, a well-known non-steroidal anti-inflammatory drug (NSAID), has in addition broad spectrum anti-viral activity in the laboratory including on SARS-Cov-2 virus. This trial is to observe the likelihood of efficacy and safety of Indomethacin in treating RT-PCR positive Covid patients

Materials and Methods
The study was done in two groups. In the first group of the study, where mild and moderate patients were involved, Propensity Score Matching was used as a methodology to compare Indomethacin and paracetamol based treatments in addition to the standard protocol for treating covid-19 patients.. Blood chemistry was collected before and after the treatment. The patients were monitored every day for clinical parameters. In this part, a patient developing hypoxia was the end point. In the second group, severe patients admitted with hypoxia were treated with Indomethacin in addition to Remdesivir, and the end point was the requirement of mechanical ventilation/admission to ICU.
Results
It was observed that patients treated with Indomethacin had a reduction in the number of days to become afebrile, reduction in cough and myalgia by half compared to the paracetamol set. Only one out of 72 patients in the Indomethacin arm of the first group required supplementary oxygen while 28 of the 72 patients required supplementary oxygen in the paracetamol arm. No one in the second group deteriorated enough to require mechanical ventilation. There wea no evidence of adverse reaction to indomethacin or deterioration of renal or liver function.
Conclusion
Indomethacin, along with standard care, seems to provide faster symptomatic relief and prevent progression of pneumonia in Covid-19 patients. It should be considered to replace paracetamol when there is no contraindication for its use.