bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Clostridioides difficile strains, the disease severity and the microbial changes they induce
Authors: Rohana Hanan , Azrad Maya , Nitzan Orna , Adler Amos , Koren Omry , Peretz Avi
Published: June 2020

Background
In recent years, the global incidence of Clostridioides difficile infection has increased dramatically, with the emergence of hyper-virulent strains. The characteristics of the different strains, the severity of the disease they cause, their susceptibility to antimicrobial agents, and the changes they inflict on the gut microbiome, have not yet been comprehensively studied.
Results
Using Multilocus Sequencing Typing (MLST) analysis, the different sequence types (STs) of 70 clinical isolates were determined. The most frequent strains were ST04 (22.5%), ST37 (12.7%), ST104 (8.5%), ST42 (7%), and ST02 (7%). The different STs were divided to different phylogenetic lineages (clades), with clade 1 forming the majority of cases (81.4%, 57/70). A significant correlation was found between ST and age (p = 0.024); patients with ST104 (n = 6) were of the lowest mean age (61.67 ± 18.8 years), while patients with ST37 (n = 9) were of the oldest mean age (79.67 ± 10.6 years). In addition, a significant correlation between ST and susceptibility to moxifloxacin was identified (p = 0.001); 15 ST04 isolates (93.7%, n = 16) were resistant, while all ST42 (n = 5) and ST104 isolates (n = 6) were sensitive. Significant correlations were found between clade and binary toxin gene presence (p = 0.002), with 93% of the isolates belonging to clade 1 lacking the gene. Furthermore, significant correlations were found between clade and susceptibility to both metronidazole and vancomycin (p = 0.024, p = 0.035, respectively). Differences in intestinal microbiome were affected by age, clade distribution and ST.
Conclusions
By defining the characteristics of the different strains and clades, clinicians can choose medical interventions based on the predicted response or disease severity associated with each strain, enabling new advances in the field of personalized medicine.
Mediation of the salicylic acid pathway by ROS1 in response to abiotic stresses
Authors: Yang Liping , Jin Taicheng , Wu Yanju , Lang Chenjing , Meng Dawei , Wang Yue
Published: June 2020

DNA methylation plays an important role in the growth and development of plants and in response to various abiotic stresses. Salicylic acid (SA) is an important signaling molecule that is synthesized by plants and induces the expression of defense genes. In this paper, we investigated the epigenetic regulation mechanism by which an upstream regulator ACD6 in the SA pathway, ABA pathway-related gene ACO3 , and stress resistance gene GSTF14 in response to various abiotic stresses. The results demonstrated that abiotic stresses, including drought, cold, and salt stresses, induced the demethylation of the repeats in the promoters of ACD6 , ACO3 , and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that transcriptional activation of ACD6 and GSTF14 was mainly dependent on ROS1-mediated DNA demethylation when Arabidopsis plants under cold stress, suggesting that ROS1 plays an important role in the process of defense genes in the SA pathway and stress resistance gene GSTF14 in response to abiotic stresses.
Case Report of a Patient with Hemophagocytic Lymphohistiocytosis in Small Cell Lung Cancer
Authors: Xu Wenyan , Guo Zhenxing
Published: June 2020

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and almost universally fatal disease in adults. Due to lack of recognition, under-diagnosis or delayed diagnosis, malignancy related HLH has a poor outcome in adults.Case Presentation A 60-year-old-female patient was admitted to our hospital with a three day history of weakness and anorexia. Physical examination revealed severe pallor without lymphadenopathy or hepatosplenomegaly. Initial blood test showed hemoglobin level of 26 g/L and platelet count of 76×109/L. Later the patient experienced sustained fever with a maximum temperature of 40°C for one week without any obvious infective symptoms. Biochemical examination revealed high serum ferritin and low natural killer cell viability. The bone marrow morphology showed hemophagocytosis and infiltration with metastatic small cell lung cancer (SCLC). The patient was diagnosed as hemophagocytic lymphohistiocytosis associated with SCLC and underwent chemotherapy. However, the patient progressed rapidly and died within 2 weeks. Conclusion We reported the first HLH case with SCLC. It is critical to have an early identification of HLH in SCLC patients.
Virtual learning solutions during the COVID-19 pandemic a University Italian Ophthalmology Department Perspective
Authors: Mastropasqua Leonardo , d'aloisio rossella , Brescia Lorenza , Toto Lisa , Mastropasqua Rodolfo , Agnifili Luca
Published: June 2020

Background

Few months after the COVID-19 pandemic burst, many aspects of the human life, including education, dramatically changed. Because of the lockdown measures taken to limit the virus spread in Italy, in-person teaching and learning have been interrupted in all health care disciplines and readapted in virtual formulae.
Methods

As an academic ophthalmology department, we had to maintain the educational needs of medical and orthoptic students, internships, surgical training of residents, as well as to cover the scientific update of health care personnel (HCPs), and the continuation of research and academic activities. To assure these needs we ideated an educational strategy and a team, which was then translated on a multichannel virtual platform created with Microsoft Teams.
Results

In this platform there were twenty-one channels organized in a public view mode, open to all Team members, or in private view mode to separate non-permanent HCPs, internships, residents, and students’ tasks, from permanent HCPs tasks. Virtual channels were dedicated to provide theoretical lessons, clinical cases, surgical video, internal meetings and webinar, to offer news from scientific societies, requests of appointments from biomedical companies, links with ophthalmological websites, to move forward research projects, to participate at institutional academic duties, and to obtain feedbacks from users. Residents continued their training on surgery using a surgical simulator, after consulting an agenda uploaded into the dedicated virtual channel.
Conclusions

These positive initial results should represent a boost to rapidly proceed with the development of even more versatile virtual learning solutions, given that the forecasts for the duration of the COVID-19 pandemic are not encouraging.
ERβ1 Expression Patterns Have Different Effects On EGFR TKIs Treatment Response in EGFR Mutant Lung Adenocarcinomas.
Authors: Zhang Lijuan , Tian Meng , Lin Jiamao , Zhang Jianbo , Wang Haiyong , Li Zhenxiang
Published: June 2020

Background: Estrogen receptor β (ERβ) can regulate cellular signaling through non-genomic mechanisms, potentially promoting resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanisms underlying the ERβ-mediated resistance to EGFR TKIs remain poorly understood. Methods: qRT-PCR was performed to investigate ERβ1 and ERβ5 expression levels in cell lines. The localization of ERβ and ERβ1 within cells was assessed using immunocytochemistry and immunofluorescence. The effect of estradiol and/or gefitinib on EGFR signaling pathways was determined by western blot. Cell viability and colony formation assays were used to assess gefitinib response for different cell lines. The apoptosis was verified by tunel and western blot. Immunohistochemistry was used to assess the expression of ERβ1 in lung adenocarcinoma tissues. Patient survival was estimated using the Kaplan-Meier method, and comparisons between groups were conducted using log-rank tests. Results: PC9 cell lines stably overexpressing ERβ1 or ERβ1/ERβ5 were established successfully. Immunofluorescence revealed that ERβ5 overexpression partly retained ERβ1 in the cytoplasm. Immunoblotting analyses revealed that EGFR pathway activation levels were higher in PC9/ERβ1/5 cells than those in PC9/ERβ1 or control PC9 cells. In the presence of estradiol, PI3K/AKT/mTOR pathway activation levels were higher in ERβ1/5-expressing cells than those in ERβ1-expressing cells. Additionally, PC9/ERβ1/5 cells were less prone to the cytotoxic and pro-apoptotic effects of gefitinib compared with PC9/ERβ1 or control PC9 cells. Conclusion: Cytoplasmic ERβ1 was associated with poor progression-free survival in lung cancer patients treated with EGFR TKIs. These results suggest that anti-estrogen therapy might reverse EGFR TKI treatment resistance to some extent in selected patients.
Comparative Effects Between High-intensity Atorvastatin and Rosuvastatin on New Onset Diabetes Mellitus and Cardiovascular Outcome
Authors: Choi Jah Yeon , Choi Cheol Ung , Choi Byoung Geol , Park Yoonjee , Kang Dong Oh , Jang Won Young , Kim Woohyeun , Na Jin Oh , Kim Jin Won , Kim Eung Ju , Rha Seung-Woon , Park Chang Gyu , Seo Hong Seog , Jeong Myung Ho , Chae Sung-Chull , Seong In-Whan , Yoon Chang-Hwan , Cha Kwang Soo , Oh Seok Kyu
Published: June 2020

Background: High-intensity statin is typically used in patients with acute myocardial infarction (AMI) for secondary prevention; however, concern regarding its association with diabetes mellitus has been consistent. We investigated and compared the impact of high-intensity atorvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes with that of high-intensity rosuvastatin for a 3-year follow-up period. Methods: Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 AMI patients were enrolled from major cardiovascular centers. Among them, 2,221 patients without diabetes who had been administered with high-intensity atorvastatin (40–80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were compared and evaluated for the incidence of NODM and major adverse cardiac event (MACE) including total death, myocardial infarction, and revascularization cases in the following 3 years.Results: Baseline characteristics were comparable between two groups. Event-free survival rate of NODM and MACE was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank p-value = 0.662). Multivariable Cox analysis revealed that the statin type was not a prognostic factor in the development of NODM and MACE. Conclusions: Administering high-intensity atorvastatin and rosuvastatin in AMI patients produced comparable effects on NODM and clinical outcome, suggesting their clinical equivalence in secondary prevention.
Combined thermotherapy and cryotherapy: an effective method for the eradication of three common viruses in cultivated apples
Authors: Liu Li , Chen Xuqiang , Yan Leiyu , Jin Yuankai , Yuanji Wang , Sun Lulong , Yang Yazhou , Zhao zhengyang
Published: June 2020

Background

Apple virus disease is a serious problem affecting apple quality and crop production efficiency, and solutions are being actively and urgently explored. In particular, the cultivation of virus-free seedlings is being increasingly explored as an important technical method for facilitating the virus-free breeding of excellent apple cultivars. In this study, the apple cultivars ‘Ruiyang’, ‘Ruixue’, ‘Rui Xianghong’, and ‘Qinyue’ were used as source materials to compare the effectiveness of thermotherapy and combined thermo- and cryotherapy in eradicating apple chlorotic leaf spot virus (ACLSV), apple stem grooving virus (ASGV), and apple stem pitting virus (ASPV).
Results

Viral presence in the in vitro shoots of the four apple cultivars was detected using a reverse transcription-polymerase chain reaction. All four cultivars were found to carry ASGV and ACLSV, and ‘Rui Xianghong’ and ‘Qinyue’ additionally carried ASPV. In vitro shoots of the four cultivars were subjected to varying periods of thermotherapy (0, 2, 4, 6, and 8 weeks). Shoot tips were then removed and half were cultured directly, and the remainder were cultured after cryotherapy treatment; their survival and regeneration rates were then evaluated to determine the efficiency of virus eradication after 8 months of subculture. We showed that the eradication of viruses in each of the cultivars and their survival rate are both the highest after 4 weeks of thermotherapy. When combined with cryotherapy, application of this period of thermotherapy achieved a 100% eradication of ASPV and ACLSV, and over 50% of ASGV.
Conclusions

This study demonstrated an effective methodology for developing both new virus-free plant materials and new apple cultivars that will support sustainability of the apple production industry in China and globally.
Relationship Between Blood Glucose Variability in Ambulatory Glucose Profile and Standardized Continuous Glucose Monitoring Metrics; A Pilot Study
Authors:   Akemi 09034837312, Okada Yosuke , Torimoto Keiichi , Tanaka Yoshiya
Published: June 2020

Background: Treatment indexes using continuous glucose monitoring (CGM) have become standardized internationally, and the use of ambulatory glucose profile (AGP) is currently recommended. However, the relationship between AGP indexes and standardized CGM metrics has not been investigated. Using flash glucose monitoring (FGM), this retrospective study served to evaluate the association of the inter-quartile range (IQR) of AGP with standardized CGM metrics.Methods: The study subjects were 30 patients with type 2 diabetes mellitus (T2DM) and 23 non-diabetic patients (control group). We evaluated average IQR (AIQR) and standardized CGM metrics. The primary endpoint was the relationship between AIQR and Time in range (TIR) in a 24-hour period.Results: In the T2DM group, the AIQR was notably high and correlated negatively with TIR, and positively with Time above range, average glucose level, SD, CV, and MODD. For the T2DM group, the AIQR was notably lower in patients who achieved TIR>70%, compared to those who did not. The AIQR cutoff value, as determined by ROC analysis, was 28.3 mg/dL for those who achieved TIR>70%. No association was detected between the presence of hypoglycemia and AIQR.Conclusions: Our study is the first to provide the AIQR cutoff value for achieving the TIR target value. The range of blood glucose variability in AGP was associated with indexes of intra- and interday variations and hyperglycemia. Our results provide new perspectives in the yet-to-be established methods for evaluation of AGP in practical clinical settings.
SPL36 encodes a receptor-like protein kinase precursor and regulates programmed cell death and defense responses in rice
Authors: RAO Yuchun , JIAO Ran , WU Xianmei , WANG Sheng , YE Hanfei , LI Sanfeng , HU Juan , LIN Han , REN Deyong , WANG Yuexing
Published: June 2020

The rice (Oryza sativa) spotted leaf 36 (spl36) mutant was identified from an ethyl methanesulfonate–mutagenized Japonica cultivar Yundao population and was previously shown to display a spontaneous cell death phenotype and enhanced resistance to rice bacterial pathogens. Through the analysis of the expression of related genes, we speculate that spl36 is involved in the disease response by up-regulating the expression of defense-related genes. The results of physiological and biochemical experiments indicated that more cell death occurred in the mutant spl36, and the growth and development of the plant were affected. We have isolated SPL36 via a map-based cloning strategy. A single base substitution was detected in spl36, which results in encoding amino acid changes in the SPL36 protein. The predicted SPL36 encodes a receptor-like protein kinase precursor that contains repeated leucine domains and may be involved in stress response of rice. In the salt treatment experiment, we found that the mutant spl36 showed sensitivity to salt. Therefore, SPL36 may negatively regulate salt stress-related responses.
The first report of the most important sequential differences between COVID-19 and MERS viruses by attribute weighting models, the importance of Nucleocapsid (N) protein
Authors: Ebrahimi Mansour , Novikov Boris , Ebrahimie Esmaeil , Spilman Alexey , Ahsan Reza , Tahsili Mohammad Reza , Najafi Mojtaba , Navvabi Samaneh , Shariaty Faridoddin
Published: June 2020

COVID-19 and the Middle East respiratory syndrome-related coronavirus (MERS) viruses are from coronaviridae family; the former became a pandemic while the latter confined to a limited region. Their pathogenicity and infection rates are also different; the high mortality rate for MERS with low spreading capability. To investigate the possible structural changes at RNA sequences of both virus, 1621 and 125 sequences of COVID-19 and MERS downloaded and converted to polynomial datasets and seven attribute weighting (feature selection) approaches have been used for the analysis of genomic sequences of COVID-19 and MERS viruses. The end nucleotide sequences (from 29288 to the end genome positions) selected by the most attribute weighting models to be significantly different between two virus classes followed by smaller piece at 5700 and 1750 and 7600 nucleotide positions. These parts encode Nucleocapsid (N), Papin-like protease (NSP3) and NSP4 proteins of COVID-19. The finding for the first time reports the structural differences between two important viruses at the sequential level and paves the road to decipher new emerging COVID-19 virus high pathogenicity.
Gastrointestinal parasitic infection in Gir Cattle (Bos primigenius indicus) and Jaffrabadi Buffalo (Bubalus bubalis) from Junagadh, Gujarat, India
Authors: Raval Jatin V. , Sachaniya Riddhi M.
Published: June 2020

Coprological analysis was performed to check the presence and previlance of gastrointestinal parasites. One hundred seventy six bovine faecal samples were studied. The study reported the presence of parasitic stages of Balantidium coli, Buxtonella sulcata, Trichostrongylus spp., Toxocara vitulorum, Fasciola spp., Strongyloid spp., and Paraamphistomum spp. 43.51 % (n = 108) faecal samples from Gir cattle (Bos primigenius indicus) were positive for Gastrointestinal parasitic infections. and 36.76 % (n = 68) faecal samples from Jaffrabadi Buffaloes (Bubalus bubalis) were positive for Gastrointestinal parasitic infections. In Cattle Balantidium coli was found highest (20.37 %) and in Buffaloes Buxtonella sulcata was found highest (8.82%). the highest incidence was recorded during august for both cattle (6.48 %) and buffalo (7.35 %). Gastrointestinalparasitic infections in claves (< 12 Months) was higher than older (> 60 Months) and adult animals (12-60 Months). Season wise gastrointestinal parasitic infections in cattle were reported maximum (23.15 %) during monsoon. Maximum prevalence in buffalo was reported during Monsoon (16.18 %). similarly, females recorded higher infection rates than malesfor both cattle and buffalo.
β -Cell Function in Black South African Women: Associations With Insulin Clearance And Ectopic Fat
Authors: Smidt Melony Cathlin Fortuin-de , Mendham Amy E , Hauksson Jon , Alhamud Ali , Stefanovski Darko , Hakim Olah , Swart Jeroen , Goff Louise M , Kahn Steven E , Olsson Tommy , Goedecke Julia H
Published: June 2020

Background: The role of ectopic fat, insulin secretion and clearance in the preservation of β-cell function in obese, black African women who typically present with hyperinsulinemia is not clear. We aim to examine the associations between disposition index (DI, a measure of β-cell function), insulin secretion and clearance and ectopic fat deposition. Methods: This is a cross-sectional study of 43 obese (BMI 30-40 kg/m2) black South African ( women (age 20-35 years) without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently-sampled intravenous glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) volume (magnetic resonance imaging), intramyocellular (IMCL) and extramyocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance before (β 55.80, p=0.002) and after adjusting for hepatic insulin extraction. Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (p=0.033) and lower hepatic insulin extraction (p=0.022) associated with lower VAT, independent from SI, rather than with ectopic fat. Conclusion: Peripheral insulin clearance emerged as an important determinant of DI, independent from hepatic insulin extraction. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, was associated with both lower insulin secretion and higher hepatic insulin extraction, independent from SI, and may provide a novel explanation of these findings in obese black South African women.
Advanced Chelate Technology Based Trace Minerals Improve Growth Performance, Mineral Digestibility, Tibia Characteristics, and Antioxidant Status in Broiler Chickens
Authors: Ghasemi Hossein Ali , Hajkhodadadi Iman , Hafizi Maryam , Taherpour Kamran , Nazaran Mohammad Hassan
Published: June 2020

Background: Compared to the corresponding source of inorganic trace minerals (TM), chelated supplements are characterized by better physical heterogeneity and chemical stability and appear to be better absorbed in the gut due to possibly decreased interaction with other feed components. This study was designed in broiler chickens to determine the effects of replacing inorganic trace minerals (TM) with an advanced chelate technology based supplement (Bonzachicken) on growth performance, mineral digestibility, tibia bone quality, and antioxidant status. A total of 625 male 1-d-old broiler chickens were allocated to 25 pens and assigned to 5 dietary treatments in a completely randomized design. Chelated TM (CTM) supplement was compared at 3 levels to no TM (NTM) or inorganic TM. A corn–soy-based control diet was supplemented with inorganic TM at the commercially recommended levels (ITM), i.e., iron, zinc, manganese, copper, selenium, iodine, and chromium at 80, 92, 100, 16, 0.3, 1.2, and 0.1 mg/kg, respectively, and varying concentration of CTM, i.e., match to 25, 50, and 100 % of the ITM (diets CTM25, CTM50, and CTM100, respectively). Results: All diets, except diet CTM25, increased average daily gain (ADG), European performance index (EPI), and serum total antioxidant capacity compared to the NTM diet (P < 0.05). Broilers fed the CTM100 diet had lowest overall FCR and highest BWG, EPI, tibia ash, zinc, and manganese contents (P < 0.05). The tibia phosphorus content and apparent ileal digestibilities of phosphorus, zinc, and manganese were lower in the ITM group compared with the CTM50 and CTM100 groups (P < 0.05). Broiler chickens fed any of the diets exhibited higher serum glutathione peroxidase and superoxide dismutase activities and lower malondialdehyde level than those fed the NTM diet, where the best values were found for CTM100 treatment (P < 0.05). Conclusions: These results indicate that while CTM supplementation to 25 and 50% of the commercially recommended levels could support growth performance, a totally replacing ITM by equivalent levels of CTM could also improve growth performance, bone mineralization and antioxidant status of broiler chickens under the conditions of this study.
Vitrification of in Vivo-derived Porcine Morulae and Blastocysts Alters Metabolic and Stress Response Pathway Alterations
Authors: Cuello Cristina , Martinez Cristina A. , Cambra Josep M , Parrilla Inmaculada , Rodriguez-Martinez Heriberto , Gil Maria A , martinez Emilio A
Published: June 2020

BackgroundDespite reported promising farrowing rates after non-surgical and surgical transfers of vitrified in vivo-derived porcine morulae and blastocysts (range: 70-75%), their pregnancy loss is yet higher (10-20%) than it is for fresh embryos (< 2.5%). The present study was designed to investigate whether vitrification would affect the transcriptome of porcine morulae and blastocysts, using microarrays and qRT-PCR validation. Material and methods and resultsMorulae and blastocysts were collected from weaned sows (n=13) by laparotomy at Day 6 (Day 0=start of estrus). Of each embryo category, 50 morulae and 50 blastocysts were vitrified (Treatment group) while fresh morulae (n=40) and blastocysts (n=40) acted as control group. After one week of storage, vitrified embryos were cultured in vitrofor 24 h after warming. Non-vitrified morulae (n=40) and blastocysts (n=40), cultured in vitro for 24 h were used as controls. After the in vitro culture period, embryo viability was morphologically assessed. A total of 30 viable embryos per group and embryonic stage(three pools of 10), were subjected to gene expressionanalysis byusing a microarray approach. A fold change cut-off of ±1.5 and a p-unadjusted <0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed morulae and blastocysts were similar to those of the control (nearly 100%, n.s.).A total of 233 DEGs were identified in vitrified morulae (38 upregulated and 195 downregulated) and 105 (112 upregulated and 93 downregulated) in vitrified blastocysts compared to the control group.Transcriptome DEG profiles were dependent on developmental stage, and GO enrichment analysis mainly related DEGs tobiological processes.The vitrification/warming impact on morulae was mostly repression of gene expression with the exception of metabolism-related pathways. In the case of blastocysts, we noted the activation of the cell cycle, cellular senescence andof signaling pathways for TFGβ, p53, FoxO and MAPK. Disruption ofmetabolic-related pathways in morulae and steroid biosynthesis and gap junctions in blastocysts could be related to impaired embryo quality and developmental potential, despite the rather high post-warming survival rates seen in vitro.ConclusionIn conclusion, vitrification modified the transcriptome of in vivo-derived porcine morulae and blastocysts, resulting in moderate gene expression changes, which may disturb subsequent embryo development and pregnancy after embryo transfer.
Clinical Characteristics of COVID-19 and the Value of Mulbsta Scoring System in Prognosis Evaluation
Authors: Wang Chao , Luo Zhixiu , Wu Junyi , Zhou Jie , Lin Yahang , Yan Guilin , Yan Manman , Wang Xi , Yu Hanhua , Zeng Xiaoyun
Published: June 2020

BackgroundCOVID-19, a worldwideinfectious disease, has killed more than 420000 people, whichis extremely harmful.MethodsIn this single-center retrospective study, we included the novel coronavirus pneumonia confirmed in our hospital. This study collected the basic information andclinical examination features.ResultsThe enrolled 704 patients were affirmed infected with 2019-nCoV by the test of throat swabs. There are 334 men and 369 women, and gender, age, combined with basic diseasesare distinct in diverse disease classification (p<0.05). From the symptom analysis, the proportion of fever over 38 degrees, dyspnea, fatigue, poor appetite and other symptoms is diverse in different types of diseases (p<0.05). As the severity of the disease increases, the median lymphocyte count decreases, C-reactive protein increase, erythrocyte sedimentation rateincrease, albumin decrease, pleural effusion increase, D-Dimer and NT-proBNP increase significantly (p<0.05).As the disease severity increases, the average value of MuLBSTA score obviously ascend (p<0.05), MuLBSTA scoring system predicts novel coronavirus pneumonia patients' prognosis is still insufficient, and may require additional indicators including anorexia, fatigue, C reactive protein, etc (p<0.05).ConclusionThe MuLBSTA evaluation system has certain value for the evaluation of the disease, but it needs to be improved.
lncCRLA Enhanced Chemoresistance in Lung Adenocarcinoma That Underwentepithelial-mesenchymal Transition
Authors: Min Weili , Sun Liangzhang , Gao Xiao , Zhang Shuqun , Zhao Yang
Published: June 2020

BackgroundEMT confers increased metastatic potential andtheresistance to chemotherapiesto cancer cells.However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear.MethodsAnticancer effects were determined by MTT, soft agar, cell cycle, propidium iodide and Annexin V analysis. The effect of drugs on tumor growth was assessed using patient-derived xenograft model and nude mice model.Morphology of tumor cells were observed by phase contrast microscopy. Proteins interactions were tested by western blot and coimmunoprecipitation. Immunohistochemistry and LNA ISH were performed to determine protein and lncRNA expression. Candidate lncRNA was screened out by microarray.Resultsc-Src-mediated Caspase-8 phosphorylationessential for EMT in lung adenocarcinoma cell linespreferentially occurs in cells with themesenchymal phenotype,resultingin chemoresistance tocisplatin plus paclitaxel in patients with resectable lung adenocarcinoma and a significantly worse5-yearPFS. Cisplatin killedlung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency ofCaspase-8, during which FADDinteracted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated andinhibited RIPK1-induced necroptosis byimpairingRIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinibmitigatedc-Src-mediated phosphorylationof Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib.Conclusionsc-Src-Caspase-8 interaction initiatesEMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIPregimen was lethal.
Dynamic alterations of myeloid-derived suppressor cells and CD68+CD163+M2-like macrophages of non-small cell lung cancer patients in radiotherapy
Authors: Lv Minghe , Zhuang Xibing , Shao Shali , Li Xuan , Cheng Yunfeng , Wu Duojiao , Wang Xiangdong , Qiao Tiankui
Published: June 2020

BackgroundRecent studies showed that myeloid-derived suppressor cells (MDSCs) and M2-like macrophages are involved in the treatment of non-small cell lung cancer (NSCLC) as immunosuppressive cells; however, the changes of MDSCs and M2-like macrophages, and their prognostic value are rarely unknown in NSCLC patients during radiotherapy. In this article, we aim to explore dynamic alteration of the circulating MDSCs and M2-like macrophages, to examine their relationship, and to evaluate their prognostic value for NSCLC patients in radiotherapy.Method:Peripheral blood mononuclear cells from healthy controls and NSCLC patients in radiotherapy were isolated to examine the circulating MDSCs and M2-like macrophages. The peripheral MDSCs defined as CD11b+CD33+HLA-DR− and M2-like Macrophages signified as CD68+CD163+ were determined by flow cytometry. 40 plasma inflammatory cytokines were measured by multiplex ELISA.ResultsCompared with health controls, the percentages of MDSCs and CD68+CD163+M2-like macrophages of NSCLC patients were significantly elevated, and were distinctly higher in NSCLC patients in radiotherapy than in pre-radiotherapy. Moreover, MDSCs correlated positively with CD68+CD163+M2-like macrophages in NSCLC patients in radiotherapy and post-radiotherapy. Interestingly, the alterations of the percentages of MDSCs and CD68+CD163+M2-like macrophages in RT were irrelated with radiotherapy area. During radiotherapy, the proportions of MDSCs were clearly increased in adenocarcinoma patients but not in squamous carcinoma patients, while the proportions of CD68+CD163+M2-like macrophages were markedly elevated in squamous carcinoma patients but not in adenocarcinoma patients. In addition, the percentages of MDSCs and CD68+CD163+ M2-like macrophages were also increased in NSCLC patients reached PR in radiotherapy compared to NSCLC patients reached SD and PD. IL-1ra and MIP-1β have a positive relation with MDSCs or M2 macrophages in NSCLC patients in radiotherapy, and Eotaxin was correlated with CD68+CD163+M2-like macrophages but not MDSCs in NSCLC patients after radiotherapy.ConclusionsThe dynamic alterations of MDSCs and M2-like macrophages, as well as their connection with plasm inflammation cytokines, could provide potentially prognostic and sensitive markers for NSCLC patients in radiotherapy.Trial Registration: Jinshan Hospital of Fudan University, IEC-2020-S01. Registered 22 May 2020.
Sinusoidal endothelial cell progenitor cells promote tumor progression in the patients with hepatocellular carcinoma.
Authors: Feng Ya-xing , Li Wei , Wen Xu-dong , Zhang Ning , Yang Zhan-yu , Liu Wei-hui
Published: June 2020

Objective: Since sinusoidal endothelial cell progenitor cells (SEPCs) play great roles in liver regeneration, it is necessary to elucidate that whether these SEPCs participate in tumor progression of hepatocellular carcinoma (HCC).Methods: A total of 45 patients with primary HCC, who received liver resection, were included in this study. The liver tumors were removed from patients and partial tissues were prepared to identify SEPCs by double staining of CD133/CD45 and CD133/CD31 at the same location. Blood samples were correspondingly collected to examine liver function parameters and tumor markers. The demographics and clinic-pathological characteristics of the patients were all collected for correlation analysis with SEPCs.Results: SEPCs were observed within abundant of blood vessels in HCC nodules of all the 45 patients, but no SEPCs were detected in the tumor-adjacent tissues. The number of SEPCs was correlated with the expression levels of HCC tumor markers α-fetoprotein (AFP) and CA199. There was a positive correlation between the expressions of SEPCs markers and the diameters of HCC tumors in differently differentiated specimens (P<0.01). The expressions levels of SEPCs markers in poorly differentiated HCC patients were significantly higher than those in the moderately and highly differentiated HCC patients (P<0.05).Conclusions: SEPCs are in close connection with HCC progression, and they may potentially act as prognosis and metastasis predicting index and even therapeutic candidates of HCC.
Antimicrobial Resistance of Pseudomonas Aeruginosa Isolated From Patients With Wound Infection in Ethiopia. A Systematic Review Article 
Authors: Gebreegziabher Gebremichael , Tesfahuneygn Gebrehiwet , Gebrewahd Aderajew , Aregay Abraham
Published: June 2020

Background: Infectious diseases have been major cause of morbidity and mortality all over the globe. The ability of bacterial pathogens to adapt and overcoming to treat by different antibiotics has been challenging in patient management. The antimicrobial resistance rates of Pseudomonas aeruginosa are known to fluctuate extensively in different settings. Active inspection of trends in antibiotic resistance of Pseudomonas aeruginosa is essential for the selection of suitable antimicrobial agent for empirical therapy. The objective of our systematic review was to determine the national antimicrobial resistance profile of Pseudomonas aeruginosa isolated from patients with wound infection in Ethiopia. Methods: We searched the Pub Med database in July and August 2018. We used the term ‘antimicrobial resistance, Pseudomonas aeruginosa, wound and Ethiopia’ to find articles published from 2011 to 2018 September. Only articles in English language were included. Full-text articles were incorporated if they reported the percentage of antibiotic resistance among clinical isolates of pathogenic bacteria collected from patients in any of the regions of Ethiopia. For overlapping studies reporting on the same clinical isolates, same study period and place, only the study with the largest sample size was included.Results: From the 173 Pseudomonas aeruginosa isolates 99.5%, 95% of the isolates were resistant to ampicilin and Amoxicillin Clavulanic Acid respectively. From the isolates 28.8%, 29.7% and 39.6% of them were resistant to Gentamicine, ciprofloxacin and Ceftazidime respectively. Most of the isolates have limited susceptibility to ampicillin, Amoxicillin Clavulanic Acid, tetracycline, cotromoxazole, chloramphenicol and ceftriaxone.Conclusion: Antimicrobial resistance is likely to become a challenge in Ethiopia and may be exacerbated by overuse of antibiotics, the lack of oversight of antibiotic prescription, and the lack of relevant local data on antimicrobial resistance. Therefore, existing antimicrobial stewardship programmes should be strengthened or, where they are not yet in place, they should be developed and implemented in all regional referral hospitals in response to these challenges and Health research institutes. Antimicrobial surveillance also needs to be strengthened.
Effect of sugammadex on postoperative pulmonary complications in patients with respiratory dysfunction after laparoscopic gastric or intestinal surgery: A retrospective study
Authors: Ji Yiqin , Yuan Hui , Chen Yijun , Zhang Xincai , Wu Fan , Tang Wan , Lu Zihui , Huang Changshun
Published: June 2020

Background

Use of sugammadex is associated with fewer postoperative pulmonary complications. This study investigated the relationship between sugammadex and postoperative pulmonary complications (PPC) in specific patients with respiratory dysfunction.
Methods

The authors reviewed the electronic medical and anesthesia records of patients with respiratory dysfunction who had laparoscopic gastric or intestinal surgery at a single center between May 01, 2018, and December 31, 2019. The patients were divided into the sugammadex group and the non-sugammadex group, based on whether or not they received sugammadex. Binary logistic regression analyses were used to characterize the differences in incidence of PPC.
Results

A total of 112 patients were included, of which 46 patients (41.07%) received sugammadex. In the logistic regression analysis, the incidences of PPC were fewer in the sugammadex group. Postoperative fever [Odds Ratio (OR) 0.330; 95% Confidence Interval (CI) 0.137–0.793, p = 0.0213], postoperative ICU admission (OR 0.204; 95% CI 0.065 to 0.644, p = 0.007), cough (OR 0.143; 95% CI 0.061 to 0.333, p < 0.001), pleural effusion (all) (OR: 0.280; 95% CI 0.104 to 0.759, p = 0.012), pleural effusion (massive) (OR: 0.142; 95% CI 0.031 to 0.653, p = 0.012), and difficulty in breathing (OR: 0.111; 95% CI 0.014 to 0.849, p = 0.039) showed significant differences between the two groups.
Conclusions

Sugammadex-mediated reversal of neuromuscular blockade can reduce the PPC in patients with respiratory dysfunction.
Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1
Authors: He Haining , Yang Huanqing , Zhang Wei , Xie Zuoquan , Zhang Minmin , Xu Hua , Liu Yuanyuan , An Na , Hong Bo , Yan Feng , Yue Ling , Wang Jinghua , Xiao Shifu , Wang Tao
Published: June 2020

Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease with the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) imbalance. Altered microRNAs (miRNA) associated with BACE1 may be potential biomarkers for aMCI diagnosis. The aims of this study were to find an effective diagnostic model for aMCI, and to explore the modulation of candidate miRNAs on BACE1 expression.Methods: Plasma RNA was extracted from participants enrolled in China longitudinal aging study (CLAS). MiRNA profiling was performed using microarray sequencing on a discovery set, compromising five aMCI subjects that confirmed by 18F-Flutemetamol PET scan and five normal controls (NC). Quantitative reverse transcription PCR was used to validate the expression levels of differently expressed miRNAs on an analysis set (20 aMCI subjects and 10 NC). Diagnostic capability of candidate miRNAs was assessed in a validation set (40 aMCI subjects and 40 NC). Modulation of candidate miRNAs on BACE1 was explored in rat and human hippocampal neurons in vitro through transfection of miRNA mimics or inhibitor lentivirus.Results: In discovery set, we verified 46 significantly differentially expressed miRNAs between aMCI and NC groups (P<0.05). Among these, 33 miRNAs were down-regulated and 13 miRNAs were up-regulated. In analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p also significantly decreased in aMCI group. Four miRNAs above and miR-107 which was found to decline in previous study were selected as potential biomarkers. A diagnostic model consists of five miRNAs above had an outstanding diagnostic accuracy (81.25%) to diagnose aMCI. Except for miR-134-3p, other four miRNAs modulated BACE1 expression and C-terminal fragments-beta production effectively in rat hippocampal neurons in vitro. Similar modulation of miR-1185-2-3p and miR-1909-3p were confirmed in human hippocampal neurons in vitro.Conclusion: A diagnostic model consists of five plasma miRNAs could be novel biomarker for aMCI diagnosis. These miRNAs might be involved in pathogenesis of AD through regulating expression of BACE1.
Construction and Investigation of circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer
Authors: Wu Ming , Sang Meijie , Pan Shuo , Liu Fei , Sang Meixiang
Published: June 2020

Background

Circular RNAs (circRNAs) have drawn lots of attention in tumorigenesis and progression. However, circRNAs as crucial regulators in multitudinous biological processes have not been systematically identified in breast cancer (BC). Our research aims to explore novel circRNAs in BC and their mechanisms of action.

Methods

The circRNA expression profile data, as well as RNA-sequencing data of BC, were downloaded from public database, respectively. The differentially expressed circRNAs, miRNA, and mRNA were determined via fold change filtering. The competing endogenous RNAs (ceRNAs) network were established on the foundation of the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG analysis of the overlapped genes were performed to predict the potential functions and mechanisms of circRNAs in BC. The CytoHubba was used to determine the hub genes from the PPI regulatory network. Morever, we further used Kaplan–Meier plotter to perform survival analysis of these hub genes. Real-time PCR was used to validate the expression of the circRNAs in BC tissues.

Results

A total of seven differential expressed circRNAs were screened. After the predicted target miRNA and DEmiRNA were intersected, four circRNA-miRNA interactions including three circRNAs and four miRNAs were determined. Furthermore, the Venn diagram was used to intersect the predicted target genes and the downregulated differentially expressed genes, and screened 149 overlapped genes. Moreover, we constructed a PPI network, and selecting six hub genes, including DGAT2, ACSL1, ADIPOQ, LPL, LEP, PCK1. Moreover, the survival analysis results revealed that low expression of ADIPOQ, LPL, LEP were obviously correlated with poor prognosis of BC patients. The real-time PCR results demonstrated that, the levels of circ_0028899, circ_0000375, and circ_0000376 were significantly down-regulated in breast cancer tissues.

Conclusions

Our study constructed and analyzed a circRNA-associated ceRNA regulatory network and discovered that circ_0028899, circ_0000375, and circ_0000376 may function as ceRNAs to serve key roles in BC.
Medication Errors in Ethiopia: Systematic Review and Meta-Analysis
Authors: Endalamaw Aklilu , Dessie Getnet , Biresaw Henok , Belachew Amare , Amare Desalegn , Workineh Yinager , Birhanu Minyichil , Belay Getaneh Mulualem , Wondim Amare , Wubneh Chalachew Adugna , Birhanu Yeneabat , Asmare Yared , Wagnew Fasil , Minuye Biniam , Kefale Demoz , Nigussie Zelalem , Habtewold Tesfa Dejenie
Published: June 2020

Background: The caution of medication prescription and administration are the main physician and nursing services though there was no study to show medication error at the nation level in Ethiopia. Therefore, we estimated the national prevalence of medication errors. Methods: A systematic review of studies searched in PubMed, Scopus, African Journal of Online, and Google Scholar was done. Newcastle-Ottawa quality assessment scale was used to assess the quality status of the included studies. We employed Galbraith plot and Egger’s regression test to assess publication bias. The national prevalence of medication errors was estimated using a random-effects model meta-analysis. Moreover, subgroup analysis and meta-regression analyses were done to explore the reason of statistical heterogeneity.Results: A total of 14 studies with 5,552 administered medications and 5,661 prescription sheets were included. The overall prevalence of medication error in Ethiopia was 57.6% (95% CI: 46.2, 69.0). The pooled burden of medication administration and prescription error was 58.4% (95% CI: 51.4, 65.5) and 55.8% (95% CI: 27.0, 84.6), respectively. Omission error (38%), wrong dose (38.5%), and the wrong combination of drugs (28.7%) were highly reported types of prescription errors, whereas missed doses (57.0%), technical errors (47.0%), wrong time (35.0%), and wrong dose (30.0%) were frequently observed medication administration errors.Conclusions: Medication errors were very common in Ethiopian hospitals whereby at least one out of two medications were wrongly prescribed and administered. Our review provided a shred of up-to-date evidence for clinicians, regional, and national healthcare policymakers to appraise and improve the quality of hospitals’ inpatient care.Trail registration: The protocol is registered in the Prospero database with a registration number of CRD42019138125.
Characteristics and Risk Factors Associated with Early Mortality in Patients with Polymicrobial Bloodstream Infection: A Retrospective Clinical Study
Authors: Pang Lantian , Chen SenZhong , Ge Tiantian , Chen Chao , Xu Lichen , Wu Fengtian , Huang Chunhong , Chen Zhi
Published: June 2020

Background and Objective Polymicrobial bloodstream infections (PBSI) in hospitalized patients are associated with increased mortality, while few studies have characterized the clinical features in this population. This study aimed to assess the risk factors and short-term prognosis of PBSI in hospitalized patients.Materials and Methods 4066 patients with culture-positive blood were included between January 1, 2015 and December 31, 2017 in the First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) in our study. 218 patients were diagnosed as PBSI. The patients were divided into two groups according to the outcome after 30-day follow-up. The number of survival group were 129, while the number of non-survival group were 89. The clinical data, identified microorganisms and severity models were compared between the two groups. A cox regression model was used to identify the risk factors of 30-day mortality in PBSI patients. Five prediction models were compared by Z-test to test the value of these models to predict outcome of PBSI.Results The patients in the non-survival group were more likely to receive inappropriate antibiotic therapy at the time of PBSI and showed more severe in systemic inflammatory. They were more likely to develop to be septic shock and to be admitted in ICU than the patients in the survival group. Inappropriate initial empirical antimicrobial therapy (HR=1.713 95% CI: 1.063-2.760, p=0.027), white blood cell (HR=1.740 95% CI: 1.002-3.020, p=0.049) and platelet (HR=2.940 95% CI: 1.754-4.930, p<0.001) were independent risk factors for 30-day mortality in PBSI patients. SOFA (AUROC=0.882, 95% CI=0.832-0.922) scores was a good prognostic scoring system for predicting short-term mortality in PBSI patients. The SOFA score was more valuable than the other four models in predicting the outcome of PBSI according to the Z-test (p<0.05).Discussion and Conclusions Inappropriate initial empirical antimicrobial therapy, white blood cell and platelet were closely associated with short-term mortality.