bluuebunny/crossref_metadata_2025 huggingface dataset:
The Incidence of SARS-COV-2 Manifestations in the Central Nervous System: A Rapid Review and Meta-Analysis
Authors: Mayr Verena , Anna Glechner , Gartlehner Gerald , Klerings Irma , Lackner Peter
Published: July 2020

Background: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and presents itself mainly as a respiratory tract infection. However, reports of associated central nervous system (CNS) manifestations are increasing.Methods: We conducted this rapid review to determine the frequency of CNS manifestations of COVID-19 (CNS symptoms, acute cerebrovascular disease, and infectious/inflammatory CNS diseases) and to summarize the current evidence for direct invasion of the CNS by SARS-CoV-2. An information specialist searched Ovid MEDLINE, the CDC: COVID-19 Research Articles Downloadable and WHO COVID-19 Databases, CENTRAL, and Epistemonikos.org on May 13, 2020. Two reviewers screened abstracts and potentially relevant full-text publications independently. The data extraction, assessment of risk of bias,and certainty of evidence using GRADE was done by one reviewer and double-checked by another. If possible and reasonable, a meta-analysis was carried out.Results: We identified 13 relevant studies (four cohort studies, nine case studies) with a total of 866 COVID-19 patients.In a Chinese cohort, dizziness (16.8%; 36 of 214) and headache (13.1%; 28 of 214) were the most common CNS symptoms reported. A meta-analysis of four cohort studies including 851 COVID-19 patients showed an incidence of 3.3% (95% CI: 2.2–4.9) for ischemic stroke (follow-up: one to five weeks). In 13 of 15 encephalitis case studies, PCR testing of the cerebrospinal fluid did not detect any virus components.Conclusion: CNS manifestations occur frequently in patients with COVID-19. It is important to integrate neurologists into the multiprofessional COVID-19 treatment team to detect neurological complications early and to treat them correctly.
Clinical Characteristics of 107 Patients with COVID-19 in Ningbo, China: Single Center Experience Outside Hubei
Authors: Wu Boming , Li Junjie , Xuan Hongping , Zheng Nanhong , Ye Honghua , Hu Yaoren , Chen Tong’en , Ying Hao , Fan Lingyan , Xie Qing , Sheng Zike , Ying Yin
Published: July 2020

Background Since December 2019, there has be an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Nowadays, it rapidly spread across the country and then the worldwide. We aimed to investigate the clinical characteristics of patients with COVID-19.Methods The patients with confirmed COVID-19 admitted between January 25 and February 10, 2020, were enrolled. Epidemiological, demographic, clinical, laboratory, radiological data, and antivirus therapies, were retrospectively collected and analyzed. The 90-day follow-up of these patients was also performed.Results A total of 107 patients were included. The median age was 55.0 years (range from 18.0 to 85.0 years), and 72 (67.3%) were female. Ninety-three (86.9%) of the patients had a history of contacting with residents from Wuhan (n=31), or contacting with confirmed COVID-19 patients (n=62) within 2 weeks. Fifty-eight (54.2%) had a family cluster onset. Fever and cough were the most common symptoms. Only two patients had diarrhea. The most common underlying disease was hypertension. Lymphopenia was observed in 26 patients. Fifty-two patients with an elevated level of IL-6. On admission, bilateral patchy shadowing and ground-glass opacity were the typical radiological findings on chest computed tomography. Six patients had an intensive care unit (ICU) stay. Antivirus therapy was performed to all patients. 105 patients discharged with an improved condition, and no death was occurred during our 90-day follow-up for these patients.Conclusions Patients with COVID-19 in our hospital had relatively mild symptoms, and good prognosis. This study also highlights the importance of human-to-human transmission in COVID-19.
Identification and Characterization of Heat-Responsive miRNAs and their Regulatory Network in Maize
Authors: Zhao Yang , Wei Qiye , Chen Tianci , Xu Lijuan , Liu Jing , Zhang Xingen , Han Guomin , Ma Qing
Published: July 2020

Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs, which have been demonstrated to play essential roles in plant growth and development, and in responses to abiotic stress. Heat stress is one of the most serious stresses that affecting crop yield and quality, however, the related regulatory mechanisms of miRNAs remains poorly understanding in maize. Results: In this study, a total of 340 miRNAs, including 215 known and 125 novel members, were identified from maize seedlings under heat stress (MH) and control conditions (MC) using high-throughput sequencing approach. The 215 known miRNAs can be further divided into 40 different families, and 21-nt miRNAs were found to be most abundant among the known miRNAs. Thirty-five miRNAs, including 26 known and 9 novel members, were significantly different expressed between MC and MH libraries. Furthermore, 174 target genes were predicted to be cleaved by 115 miRNAs using degradome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for these targets to explore the biological function and pathways involved. Based on the relationships of miRNAs, target genes and the enriched results, a regulatory network was constructed for the miRNAs and their respective target genes, and 16 significantly differently expressed miRNAs (DEMs) were involved in the network. Conclusions: The results revealed novel insights into the roles of miRNAs in heat stress response and provided a useful foundation for understanding the regulatory mechanisms of heat-responsive miRNAs in maize.
Multiple Insecticide Resistance Target Sites in Adult Field Strains of An. Gambiae s.l. From Southeast Senegal.
Authors: Diouf El hadji , Niang El hadji Amadou , Samb Badara , Diagne Cheikh Tidiane , Diouf Mbaye , Konaté Abdoulaye , Dia Ibrahima , Faye Ousmane , Konaté Lassana
Published: July 2020

Background: Malaria prevention strategies are based on the use of long-lasting insecticide-treated mosquito nets (LLINs), indoor residual spraying of insecticides (IRS) and seasonal malaria chemoprevention (SMC). The combination of these strategies with artemisinin-based combination therapy (ACTs) has led to a significant reduction in malaria cases. However, malaria remains a major public health issue in most sub-Saharan African countries. Indeed, the resistance of vectors to most WHO-approved insecticides could jeopardize vector-control strategies. This study examines insecticide resistance and associated genetic mutations among malaria vectors in southeast Senegal. Methods: The study was conducted in October and November 2014 in two sites in southeast Senegal. An. gambiae s.l. populations were sampled from Kedougou (Kedougou district) and Wassadou-Badi (Tambacounda district) and were evaluated for insecticide resistance according to WHO susceptibility tests. Specimens were 3 to 5-day-old adults raised from collected larvae. Eleven insecticides belonging to the four known classes of insecticides were assessed. Mosquito species were identified and mutations associated with insecticide resistance (ace-1, rdl (A296S or A296G), Vgsc-1014F and Vgsc-1014S) were determined. Results: A total of 3,742 An. gambiae s.l. were exposed to insecticides (2,439 from Kedougou and 1,303 from Wassadou-Badi). In both sites, mosquitoes showed high levels of resistance to all the five pyrethroids tested (mortality rates ranged from 42.8 to 81.4% in Kedougou and 52.4 to 86.4% in Wassadou-Badi) as well as to dieldrin (67.8 and 83%) and DDT (12.7 and 55%). The mosquitoes were susceptible to pirimiphos-methyl (mortality rate 100%) and malathion (mortality rates 100% and 99% in Kedougou and Wassadou-Badi respectively). An. gambiae s.l. populations from Kedougou were also resistant to bendiocarb. Of the 745 An. gambiae s.l. genotyped An. gambiae s.s. (71.6%) was the predominant species, followed by An. arabiensis (21.7%), An. coluzzii (6.3%) and hybrids (An. gambiae s.s./An. coluzzii; 0.4%). The Vgsc-1014F kdr mutation was widely distributed and is predominant in An. gambiae s.s. and An. coluzzii in comparison to An. arabiensis. Vgsc-1014S was present in An. gambiae s.l. populations in Wassadou but not in Kedougou. The ace-1 and rdl mutations were more frequent in An. gambiae s.s. compared to An. arabiensis but were not detected in all populations of An. coluzzii.Conclusion: The present study demonstrates the resistance of malaria vectors to pyrethroids and organo chlorines in southeast Senegal as well as the presence of genetic mutations associated with this resistance in An. gambiae s.l. There was no Vgsc-1014S mutation in An. gambiae s.s. population in Kedougou. These findings are key for monitoring and managing the resistance of vectors to insecticides in this region.
Guidelines are Needed for Studies of Pre-Treatment HIV Drug Resistance: A Methodological Study
Authors: Mbuagbaw Lawrence , Ongolo-Zogo Clémence , Mendoza Olivia C. , Zani Babalwa , Morfaw Frederick , Nyambi Agatha , Wang Annie , Kiflen Michel , El-Khechen Hussein , Leenus Alvin , Youssef Mark , Rehman Nadia , Hermans Lucas , MacDonald Virginia , Bertagnolio Silvia
Published: July 2020

Background: The expansion of access to antiretroviral therapy (ART) has been accompanied by an increase in pre-treatment drug resistance (PDR). While it is critical to monitor the increasing prevalence of PDR across countries and populations to inform optimal regimen selection, the quality of reporting is often suboptimal, limiting the interpretation and generalizability of the results. Indeed, there is no formal guidance on how studies investigating the prevalence of drug resistance should be reported. Thus, we sought to determine the quality of reporting in studies of PDR and the factors associated with sub-optimal reporting.Methods: As part of a systematic review on the global prevalence of PDR in key populations (men who have sex with men, sex workers, transgender people, people who inject drugs and people in prisons), we searched 10 electronic databases until January 2019. We extracted information on selected study characteristics useful for interpreting prevalence data and used linear regression to determine the factors associated with reporting more items. Data were extracted in duplicate.Results: We found 650 studies of which 387 were screened as full text and 234 were deemed eligible. The included studies were published between 1997 and 2019 and included a median of 239 (quartile 1=101; quartile 3= 778) participants. Most studies originated from high-income countries (125/234; 53.0%). Of 23 relevant data items, including study design, setting, participant sociodemographic characteristics, HIV risk factors, type of resistance test conducted, definition of resistance, the mean (standard deviation) number of items reported was 13 (2.2). We found that more items were reported in studies published more recently (β=0.077; p=0.037) and in studies at low risk of bias (β= -0.599; p=0.004).Conclusions: The poor quality of reporting in studies on PDR makes characterising levels of PDR in subpopulations across countries challenging. Hence, guidelines are needed to define a minimum set of variables to be included in such studies.
Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p
Authors: Huang Chen , Luo Wenfeng , Wang Qian , Ye Yufeng , Fan Jinghui , Lin Li , Shi Congying , Wei Wei , Chen Hanwei , Wu Yangzhe , Tang Yukuan
Published: July 2020

Background: Diabetic foot is caused by ischemic disease of lower extremities of diabetic patients, and the effective therapy is very limited. Mesenchymal stem cells (MSCs) based cell therapy had been developed into a new treatment strategy for diabetic foot clinically. However, the underlying molecular mechanism remains to be fully addressed. Exosomes secreted by MSCs may play crucial role in the processes of MSCs mediated inhibition of inflammatory microenvironment as well as pro-angiogenesis of ischemic tissue of diabetic foot. Methods: Exosomes were isolated from MSCs using ultra-high centrifugation, and further characterized by the nanoparticle tracking analyzer and flow cytometry. Moreover, RNA sequencing, Western Blot, in vitro cell proliferation, in vivo pro-angiogenesis, as well as ischemic repairment of diabetic foot through rat model were performed to evaluate exosome physiological functions. Results: We found that different inflammatory cytokines (tumor necrosis factor a, vascular cell adhesion molecule-1 and interleukin-6) induced MSCs to secrete exosomes heterogeneously, including exosome size and quantity. Through RNA sequencing, we defined a new proangiogenic miRNA, miRNA-21-5p. Further knockdown and overexpression of miRNA-21-5p by manipulating MSCs validated the biological activity of exosome miRNA-21-5p, including in vitro cell proliferation, in vivo pro-angiogenesis in Chick Chorioallantoic Membrane (CAM) assay, and in vivo pro-angiogenesis experiments (tissue injury and repair) in diabetic rat models. Furthermore, we discovered that exosomemiRNA-21-5p promoted angiogenesis through upregulations of vascular endothelial growth factor receptor (VEGFR) as well as activations of serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK). Together, our work suggested miRNA-21-5p could be a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis. Meanwhile, miRNA-21-5p could be potentially developed into a new biomarker for exosomes of MSCs to treat diabetic foot. Conclusions: miRNA-21-5p is a new biomarker and a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis of diabetic foot. Our work could not only provide new scientific evidences for revealing pro-angiogenesis mechanism of MSCs, but also eventually benefit MSCs-based clinical therapy for diabetic foot of diabetes patients.
Subcutaneous injection of interferon-α2b for COVID-19: an observational study
Authors: Wang Bo , Li Diandian , Liu Tao , Wang Haohua , Luo Fengming , Liu Yanbin
Published: July 2020

Background
The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality.
Objective
The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon-α2b (IFN-α2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone.
Methods
Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN-α2b.
Results
A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN-α2b. The average length of hospitalization in the combination group (16 ± 9.7 days) was shorter than that of LPV/r group (23±10.5 days). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group. Combined therapy with IFN-α2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups.
Conclusion
Subcutaneous injection of IFN-α2b combined with LPV/r might shorten the length of hospitalization and accelerate viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.
Effects of Chromosomal Abnormalities on Assisted Reproductive Technology: A Retrospective Cohort Study
Authors: Cui Ling , Lin Yonghong , Wang Fang , Yu Xinting , Teng Wending , Xian Hong , LI Min
Published: July 2020

Background: To ascertain whether couples with chromosomal abnormalities have a difference in cumulative clinical pregnancy rate and cumulative live birth rate among assisted reproductive technology population. Methods: Design: A retrospective cohort study. Setting: Department of reproduction and infertility in Chengdu Women's and Children's Central Hospital.Patients: A total of 112 couples were in exposed group with chromosomal abnormalities and 226 couples without chromosomal abnormalities in control group included in the study, totaling 338 cases. From 1st Jan 2017 to 31st Dec 2019. Control group (infertility couples without chromosomal abnormalities) was 1:2 matched by female age, type of infertility (primary, secondary), type of assisted reproductive technology (IVF, ICSI or IUI). Results: Primary outcomes: cumulative clinical pregnancy rate and cumulative live birth rate. The results indicated that chromosomes abnormalities had no statistical difference in primary outcomes. Further analysis revealed exposed group (couples with chromosomal abnormalities) had less 2 pronuclear stage count. The times of embryo transfer by ICSI was less than IVF in exposed group. We found out only female age had an effect on the primary results and the threshold was 33.5years old.Conclusions: There were no significant differences in cumulative clinical pregnancy rate and cumulative live birth rate between two groups. But 2 pronuclear stage count, and the times of embryo transfer were affected by chromosomal abnormalities. It may be better to choose ICSI and PGT in this population.
Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology
Authors: Padwal Jennifer , Berry David B , Hubbard James C. , Zlomislic Vinko , Allen R. Todd , Garfin Steven R. , Ward Samuel R. , Shahidi Bahar
Published: July 2020

Background: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology.Methods: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. Results: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. Conclusions: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.
Chemical composition and pharmacological mechanism of Ephedra-Glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19)
Authors: Qiu Qin , Li Mingyue , Lin Haowen , Cao Shilin , Wang Qu , Li Xiaoling , Chen Zishi , Jiang Wenhao , Huang Yuge , Luo Hui , luo lianxiang
Published: July 2020

Background: Coronavirus disease 2019 (COVID-19) is currently spreading all over the world, and the prospect of a very rapid increase in COVID-19 cases prompted us to seek effective antiviral therapeutics, from the identification of possible drugs to their potential mechanisms. Purpose: The aim of this study was to explore the efficacy of the Ephedra-Glycyrrhiza (EG) drug pair on coronavirus disease 2019 (COVID-19) by network pharmacology and molecular docking. Methods: The main active compounds, target information, meridians and properties of EG were obtained through the TCMSP and ETCM databases. The targeted information of COVID-19 was acquired from the GeneCards database. EG drug pair applied diseases were analysed by DAVID and the drug-bank database, and visualized by Rstudio and Cytoscape 3.7.2. Then, we carried out targeted intersection of the EG drug pair and COVID-19 to map the compound-target-disease interactions and visualize them with Cytoscape 3.7.2 and Venny 2.1. In addition, the enrichment analysis of the GO and KEGG pathways were visualized with Rstudio and PathVisio software through the DAVID database. Finally, we carried out the molecular docking of the EG active compounds with M hydrolase (Mpro), spike protein (S protein) and angiotensin-converting enzyme 2 (ACE2), and the binding modes between GE and the protein were verified via molecular dynamics (MD) simulation. Results: We identified 112 active EG compounds by network pharmacological analysis. Drug pair enrichment analysis demonstrated that these compounds may participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signalling pathways, which had a high correlation with respiratory system, nervous system, blood circulation system and digestive system related diseases. Pathway analysis between EG and COVID-19 showed that the key targets were TNF, IL2, FOS, ALB and PTGS2. They may regulate the PI3K-Akt signalling pathway and natural killer cell-mediated cytotoxicity to play roles in immune regulation, organ protection, antiviral, immune regulation, and organ protection as well as having antiviral effects. Molecular docking results showed that the active EG compounds bind well to Mpro, S protein and ACE2. The binding modes between the active compounds of the EG and protein were verified via MD simulation. Conclusion: The EG drug pair can treat COVID-19 through multiple targets and pathways, which can provide a theoretical basis for further study of the mechanism of action of the EG drug pair on COVID-19.
Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking
Authors: Li Xiaoling , Lin Baixin , Lin Zhiping , Wang Qu , Zheng Yushi , Cui Liao , Luo Hui , luo lianxiang
Published: July 2020

Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.
Fluoroscopy-assisted percutaneous guide wire puncture for the treatment of intertrochanteric fractures with proximal femur nail anti-rotation
Authors: Xu Huazhong , Yuan Peng , Yang Yusheng , Shi Ke-qin
Published: July 2020

Background: Accurate percutaneous guide wire insertion for the treatment of intertrochanteric fractures with proximal femur nail anti-rotation(PFNA) can be a technical challenge. It is critical for the surgeon to place the implant accurately during the procedure; however, the muscles and soft tissues in the hip often make accurate guide wire insertion difficult, especially in overweight and obese patients.Purposes: The purpose of this study was to evaluate a series of patients who underwent percutaneous guide wire puncture and PFNA fixation to determine the influence of this technique on soft-tissue trauma and accuracy of guide wire placement.Methods: From June 2015 to June 2018,forty-five consecutive patients with a minimally displaced or displaced intertrochanteric fracture were treated with percutaneous guide wire puncture technique and PFNA fixation in two trauma centers. Six patients were lost to follow-up. The remaining thirty-nine patients were followed until union or a minimum of twelve months. There were thirty female and fifteen male patients with a mean age of 78.5 years old. Radiographs were used to evaluate the quality of fracture union. Intraoperative fluoroscopic views of the first puncture attempt were evaluated for the accuracy of percutaneous puncture technique.The number of puncture attempts used was recorded.Incision lengths of nail insertion were measured and recorded.Results: All fractures united. The length of the incisions ranged from 2.0 cm to 3.1 cm,with a mean of 2.5 cm.The angles between the guide wire and the axis of the proximal femur were within 3°in lateral fluoroscopic view,and ranged from 4°to 8°with a mean value of 6.3°in anteroposterior(AP) fluoroscopic views.The number of punctures in every patient were less than 2.Among forty-five patients, forty-three patients(95.6%) were punctured successfully with one pass. No complications were observed.Conclusions: Percutaneous guide wire puncture for the treatment of intertrochanteric fractures with PFNA fixation can lead to excellent outcomes, by virtue of accurate implant placement, less trauma,and fewer complications.Level of Evidence: Therapeutic level IV
Genomic Survey Sequencing, Development and Characterization of Single- and Multi-Locus Genomic SSR Markers of Elymus Sibiricus L.
Authors: Xiong Yi , Lei Xiong , Bai Shiqie , Xiong Yanli , Liu Wenhui , Wu Wendan , Yu Qingqing , Dong Zhixiao , Yang Jian , Ma Xiao
Published: July 2020

Background: Siberian wildrye (Elymus sibiricus L.) attracts considerable interest for grassland establishment and pasture recovery in the Qinghai-Tibet Plateau (QTP) due to its excellence in strong stress tolerance, high nutritional value and ease to cultivate. However, the lack of genomic information of E. sibiricus hampers its genetics study and breeding process.Results: In this study, we performed a genome survey and developed a set of SSR markers for E. sibiricus based on Next-generation sequencing (NGS). We generated 469.17 Gb clean sequence which is 58.64× of the 6.86 Gb estimated genome size. We assembled a draft genome of 4.34 Gb which has 73.23% repetitive elements, a heterozygosity ratio of 0.01% and GC content of 45.68%. Based on the gnomic sequences we identified 67,833 SSR loci and from which four hundred were randomly selected to develop markers. Finally, 30 markers exhibited polymorphism between accessions and ten were identified as single-locus SSR. These newly developed markers along with previously reported 30 ones were applied to analyze genetic polymorphism among 27 wild E. sibiricus accessions. We found that single-locus SSRs are superior to multi-loci SSRs in effectiveness.Conclusions: This study provided insights into further whole genome sequencing of E. sibiricus in strategy selection. The novel developed SSR markers will facilitate genetics study and breeding for Elymus species.
Screening of Non-catalytic Integrase Inhibitors for Anti-HIV Drug Development
Authors: Park Ki Hoon , Kim Minjee , Bae Seoung Eun , Lee Hee Jung , Kim Kyung-Chang , Choi Byeong Sun , Kim Young Bong
Published: July 2020

Background: Integrase (IN) is an essential protein for HIV replication that catalyzes insertion of the reverse-transcribed viral genome into the host chromosome during the early steps of viral infection. Highly active anti-retroviral therapy (HAART) is a HIV/AIDS treatment method that combines three or more antiviral drugs often formulated from compounds that inhibit the activities of viral reverse transcriptase and protease enzymes. Early IN inhibitors (INIs) mainly serve as integrase strand transfer inhibitors (INSTI) that disrupt strand transfer by binding the catalytic core domain (CCD) of IN. However, mutations of IN can confer resistance to INSTI. Therefore, non-catalytic integrase inhibitors (NCINI) have been developed as next-generation INIs. Methods: In this study, we evaluated and compared the activity of INSTI and NCINI according to the analysis method. Antiviral activity was compared using p24 ELISA with MT2 cell and TZM-bl luciferase system with TZM-bl cell. Each drug was serially diluted and treated to MT2 and TZM-b1 cells, infected with HIV-1 AD8 strain and incubated for 5 and 2 days, respectively. Additionally, to analyze properties of INSTI and NCINI, transfer inhibition assay and 3'-processing inhibition assay were performed. Results: During screening of INIs using the p24 ELISA and TZM-bl luciferase systems, we found an inconsistent result with INSTI and NCINI drugs. Following infection of MT2 and TZM-bl cells with T-tropic HIV-1 strain, both INSTI and NCINI treatments induced significant p24 reduction in MT2 cells. However, NCINI showed no antiviral activity in the TZM-bl luciferase system, indicating that this widely used and convenient antiretroviral assay is not suitable for screening of NCINI compounds that target the second round of HIV-1 replication. Conclusion: Accordingly, we recommend application of other assay procedures, such as p24 ELISA or reverse transcription activity, in lieu of the TZM-bl luciferase system for preliminary NCINI drug screening. Utilization of appropriate analytical methods based on underlying mechanisms is necessary for accurate assessment of drug efficacy.
Using mobile phone data for epidemiological simulations of lockdowns: government interventions, behavioral changes, and resulting changes of reinfections
Authors: Müller Sebastian A , Balmer Michael , Charlton Billy , Ewert Ricardo , Neumann Andreas , Rakow Christian , Schlenther Tilmann , Nagel Kai
Published: July 2020

Epidemiological simulations as a method are used to better understand and predict the spreading of infectious diseases, for example of COVID-19. This paper presents an approach that combines person-centric data-driven human mobility modelling with a mechanistic infection model and a person-centric disease progression model. Results show that in Berlin (Germany), behavioral changes of the population mostly happened before the government-initiated so-called contact ban came into effect. Also, the model is used to determine differentiated changes to the reinfection rate for different interventions such as reductions in activity participation, the wearing of masks, or contact tracing followed by quarantine-at-home. One important result is that successful contact tracing reduces the reinfection rate by about 30 to 40%, and that if contact tracing becomes overwhelmed then infection rates immediately jump up accordingly, making rather strong lockdown measures necessary to bring the reinfection rate back to below one.
Productivity Growth and Sectoral Interactions under Domar Aggregation: A Study for the Brazilian Economy from 2000 to 2014
Authors: Santini Theo , Araujo Ricardo
Published: July 2020

In this paper, we use the Domar aggregation approach to study the evolution of productivity growth in Brazil from 2000 to 2014, thus allowing us a disaggregated assessment of the issue. We found that the overall performance of the Brazilian economy can be explained not only by the poor performance of its sectors but also in terms of diminishing industrial density, with fewer backward and forward connections amongst industries in terms of chains of intermediate inputs. Besides, despite the relatively high density of the manufacturing sector, it performed a negative role concerning aggregate productivity growth both directly and indirectly. Directly insofar as that sector had negatives productivity growths during the period under consideration, and indirectly due to its high interconnection, which spread negative rather than positive productivity gains across the economy. Therefore, to improve the poor performance of the Brazilian economy, it is mandatory to restore the capability of the manufacturing sector of yielding and spreading productivity gains.
Deciphering Centimeter-Scale Microbial Biogeographic Patterns and Community Assembly Processes From A 3D Perspective
Authors: Xue Ran , Zhao Kankan , Yu Xiuling , Stirling Erinne , Liu Shan , Ye Shudi , Ma Bin , Xu Jianming
Published: July 2020

Background: Revealing the effects of multi-dimensional spatial distribution on microorganisms is crucial for the further understanding of microbial diversity, turnover and ecological processes. However, microbial community assembly and the factors that shape it are still unknown from a three dimensional (3D) perspective. Here, a 3D model was created by performing an exhaustive sampling strategy to a 4x4x4 soil matrix. We examined the dynamics of microbial diversity, biogeographic patterns and microbial assembly processes when transfroming sampling scheme from 2D to 3D.Results: Our results indicated that dispersion of microbial community and significance of distance decay relationship was higher in the 3D compared with 2D sampling scheme, suggesting increased microbial turnover when transforming the model from 2D to 3D. Only a small fraction of community variation can be explained by environmental, spatial factors and spatial canonical axes, possibly due to unmeasured environmental variables. The assembly of microbial community was dominated by deterministic processes that shifted from homogeneous selection to variable selection as we transformed the model from 2D to 3D. The importance of stochasticity increased when homogeneous and variable selection processes were well balanced. However, heterogeneity of existing environmental and spatial variables failed to explain the dynamics of community assembly.Conclusions: Our study revealed significant dynamics of microbial diversity and assembly processes when assessed from 2D and 3D perspectives. As microorganisms are spatially distributed in soil, this spatial dependent diversity and assembly suggests that microbial ecological questions need to be considered in more dimensions than they usually are. Further, new models that integrate all data sets are still needed to disengle the microbial processes in multiple dimensions.
Identification of TIMP2 and RAX as key regulators in chemosensitive osteosarcoma
Authors: Wang HuaBin , Liu Yuanxiang , Zeng Haitao
Published: July 2020

Background This study is trying to investigate the regulation mechanism of chemosensitive osteosarcoma. mRNA and miRNA profiles were explored between chemosensitive and chemoresistant osteosarcoma patients based on GSE39058 dataset. IPA was used for pathway and function enrichment. Another dataset GSE21257 with clinical characteristics was used for survival analysis, and 68 new enrolled osteosarcoma patients with chemotherapy responses were used for RT-PCR validation. Finally, lentiviruses infected U-2 OS cells were subjected to cell counting and real-time cell analyzer.Results A total of 567 differentially expressed genes and 34 differentially expressed miRNAs were screened out. These genes mainly involved in the biology functions of cell survival and cell proliferation, and enriched in the pathways of VEGF signaling, Paxillin signaling, and Inhibition of matrix matalloproteases. In 53 validation osteosarcoma patients from GSE21257, high-expression of TIMP2 and BAX, two common genes among the enriched biology functions, have favorable prognosis with p-values 0.052 and 0.027 respectively. In the 68 new enrolled patients, both TIMP2 and BAX were RT-PCR validated to be high-expressed in chemosensitive group with p-values 0.04 and 0.003 respectively. In addition, cell count and cell index either in TIMP2 or BAX infected U-2 OS cells were smaller compared with control cells within four consecutive days.Conclusions In summary, the biology functions of cell survival and cell proliferation were identified to be mainly inhibited in chemosensitive osteosarcoma patients. Two up-regulated genes, TIMP2 and BAX, were validated to be important regulators of cell proliferation and cell apoptosis in chemosensitive group. Further experimental evidences are still needed to consolidate this results.
Impact of Nonsteroidal Anti-Inflammatory Drug Administration for 12 Months on Renal Function
Authors: Hayashi Kazuhiro , Miki Kenji , Kajiyama Hiroshi , Ikemoto Tatsunori , Yukioka Masao
Published: July 2020

Background: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of renal complications. Resolution of renal side effects following NSAID administration has been observed following short-term use. Thus, the aim of the present study was to investigate whether switching from long-term NSAID administration to tramadol hydrochloride/acetaminophen (TA) combination tablets results in reversal of renal side effects.Methods: This was a longitudinal retrospective study of 99 patients with chronic musculoskeletal pain. The patients were administrated NSAIDs daily during the first 12 months followed by daily TA combination tablets for 12 months. Estimated glomerular filtration rate (eGFR) and serum levels of aspartate aminotransferase and alanine transaminase were measured at baseline, after NSAIDs administration, and after TA administration.Results: eGFR was significantly reduced following 12-month NSAIDs administration (median, from 84.0 mL/min/1.73 m2 to 72.8 mL/min/1.73 m2), and further reduction was prevented following the subsequent 12-month TA administration. Reduction in eGFR was less in patients who received celecoxib (median, -1.8 mL/min/1.73 m2) during the first 12 months. There was no significant difference in aspartate aminotransferase and alanine transaminase in each period.Conclusions: Thus, patients receiving NSAIDs for 12 months displayed both reversible and irreversible reduction of eGFR upon cessation of NSAIDs and switching to TA. Our data highlights the potential safety benefit of utilizing multimodal analgesic therapies to minimize the chronic administration of NSAIDs.
Neonatal SARS-CoV-2 infections: systematic review, synthesis and meta-analysis of reported cases
Authors: Raschetti Roberto , Vivanti Alexandre , Vauloup Christelle , Loi Barbara , Benachi Alexandra , De Luca Daniele
Published: July 2020

It is unclear if COVID-19 affects neonates. Some cases of neonatal SARS-CoV-2 infections have been reported but not systematically analysed. We aim to clarify the main transmission route, clinical features and outcomes of neonatal SARS-CoV-2 infections and we performed an individual patient data meta-analysis, following PRISMA guidelines, of neonates infected by SARS-CoV-2 (demonstrated by: at least one positive nasopharyngeal swab and/or the presence of specific IgM). We analysed 117 infected neonates. 68% and 32% of infections were due to environmental and vertical transmission, respectively. Approximately 55% of infected neonates developed clinically evident COVID-19. Commonest clinical features were fever (50%), gastrointestinal (43.7%), respiratory (42.2%) and neurological manifestations (20.3%). Lung imaging was abnormal in 59.4%. The lack of mother-neonate separation from birth was associated with the incidence of late SARS-CoV-2 infection (OR 5.1 (95% CI: 1.6-18); p=0.003), while breastfeeding was not (OR 0.49 (95% CI: 0.12-1.94); p=0.35).
Cryo-EM Structures of Respiratory bc1-cbb3 type CIII2CIV Supercomplex and Electronic Communication Between the Complexes
Authors: Steimle Stefan , Eeuwen Trevor Van , Ozturk Yavuz , Kim Hee Jong , Braitbard Merav , Selamoglu Nur , Garcia Benjamin , Schneitman-Duhovny Dina , Murakami Kenji , Daldal Fevzi
Published: July 2020

Respiratory electron transport complexes are organized as individual entities or combined as large super-complexes (SC). The Gram-negative bacteria deploy a mitochondrial-like cytochrome (cyt) bc1 (Complex III, CIII2), and may have specific cbb3-type cyt c oxidases (Complex IV, CIV) instead of the canonical aa3-type CIV. Electron transfer between these complexes is mediated by soluble (c2) and membrane-anchored (cy) cyts. Here, we report the first structure of a bc1-cbb3 type SC (CIII2CIV, 5.2Å resolution) and three conformers of native CIII2 (3.3Å resolution) of functional relevance. The SC contains all catalytic subunits and cofactors as well as two extra transmembrane helices attributed to cyt cy and the assembly factor CcoH. The cyt cy is integral to SC, its cyt domain is mobile and conveys electrons to CIV differently than cyt c2. For the first time, this work establishes the structural characteristics of membrane-confined and membrane-external electron transport pathways of SCs in Gram-negative bacteria.
Expression of Long-Chain Noncoding RNA GAS5 in Osteoarthritis And Its Effect on Apoptosis And Autophagy of Osteoarthritis Chondrocytes
Authors: Ji Qinghui , Qiao Xiaofeng , Liu Yongxiang , Wang Dawei , Yan Jinglong
Published: July 2020

Objective: To investigate the expression of long chain non-coding RNA GAS5 in osteoarthritis(OA) and the effect on autophagy and apoptosis of chondrocytes. Method: OA rat model was constructed and the expressions of GAS5 in articular cartilage tissues at 4 weeks(early OA) and 12 weeks(late OA) after modeling were detected. The chondrocytes of OA rat were isolated, cultured and transfected with si-GAS5 to silence the GAS5. Then the change of apoptosis and autophagy levels of OA chondrocytes were detected. The microRNA binding to GAS5 and the competitive target gene were analyzed and verified. Results: The expression of GAS5 in cartilage tissue of OA rats was higher than that of control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OA chondrocytes was increased and the apoptosis rate was decreased. GAS5 could bind with miR-144 competitively and regulate mTOR positively. The mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on cell autophagy but could not reverse the promotion on apoptosis. Conclusion: GAS5 expression was high and increased with the progression of OA. GAS5 could inhibit the autophagy and promote the apoptosis of OA chondrocytes, and the effect on autophagy may be related to the regulation on mTOR.
A Qualitative Evaluation of the Usability of a Hospital-Wide Electronic Medication Management System in the Oncology setting using the Unified Theory and Use of Technology Framework
Authors: dabliz racha , Poon Simon K. , Ritchie Angus , Burke Rosemary , Penm Jonathan
Published: July 2020

Background: In light of the complexity of the medication process and the difficultly of examining it in isolation from other interrelated processes and contextual factors, this qualitative research aims to fill the gap in the literature by cohesively determining the usability of a hospital-wide Electronic Medication Management System in a specialised oncology unit by bringing in the perspective of three key user groups. Furthermore, it demonstrates how the UTAUT can be used to guide qualitative evaluation studies in evaluating the usability of an integrated EMMS. Methods: This was a qualitative study conducted in a 12-bed hospital outpatient Oncology unit in a major teaching hospital. In-depth semi-structured interviews were performed with the doctors, nurses and pharmacists to identify user’s requirements. Data were analysed by using the UTAUT framework for analysis. Results: The UTAUT framework facilitated the evaluation of interrelated aspects and provided a structured summary of user experience usability factors. The direct cross comparison between user groups illustrated that doctors and pharmacists were generally satisfied with the facilitating conditions (hardware and training), but had varying perceptions of performance (automation, standardised protocols and communication and documented) and effort (mental and temporal demand). On the other hand, nurses were generally satisfied across all constructs. It also illustrated the key role that ‘previous system experience’ plays in developing user’s system frustrations and acted as a moderator for these constructs. Conclusion: Considering the complexity of the medication process and the difficultly of examining it in isolation from other interrelated processes and contextual factors, this study cohesively demonstrated the need to explore perceptions of usability across user groups. It illustrated that doctors and pharmacists were satisfied with the EMMS if it provided desirable utility to their practice, and nurses when the EMMS was easy to use in the nursing processes using the UTAUT framework. As multidisciplinary teams are involved in cancer care, all potential users and their requirements should be considered.