bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis
Authors: Chen Liang , An Shuoyan , Yao Guangyu , Xiong Jiasheng , Xiong Haiyan , Zhao Ping , Jiang Lufang , Hua Wei , Xiong Chenglong , Duru Firat , Jiang Qingwu
Published: June 2020

Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 p<0.0001). In the sensitivity analysis, the effect on viral clearance disappeared (OR 1.44, 95% CI: 0.87-2.37, p=0.155). The use of HCQ/CQ was associated with a higher risk of mortality (OR 1.26, 95% CI: 1.05-1.51, p<0.0001). Due to huge heterogeneity between the studies (I2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.
Transgenic and knockout analyses of Masculinizer and doublesex illuminated the unique functions of doublesex in germ cell sexual development of the silkworm, Bombyxmori
Authors: Yuzawa Tomohisa , Matsuoka Misato , Sumitani Megumi , Aoki Fugaku , Sezutsu Hideki , Suzuki Masataka
Published: June 2020

Background
Masculinizer (Masc) plays a pivotal role in male sex determination in the silkworm, Bombyx mori. Masc is required for male-specific splicing of B. mori doublesex (Bmdsx) transcripts. The male isoform of Bmdsx (BmdsxM) induces male differentiation in somatic cells, while females express the female isoform of Bmdsx (BmdsxF), which promotes female differentiation in somatic cells. However, the importance of Bmdsx in sexual differentiation in germ cells remains unclear. In Drosophila melanogaster, mechanisms regulating sexual differentiation differ between germ cells and somatic cells. dsx is not required within female or male germ cells for sexual development. However, it remains unclear whether this is also the case in other insect species.
Results
In this study, we performed genetic analyses using a transgenic line that expressed Masc, as well as various Bmdsx knockout lines. Masc-expressing females express both BmdsxF and BmdsxM and have degenerated ovaries combined with testis-like tissues, which produce sperm. We found that Masc-expressing females with a homozygous mutation in BmdsxM showed normal development in ovaries. The formation of testis-like tissues was abolished in these females. In comparison, Masc-expressing females carrying a homozygous mutation in BmdsxF exhibited almost complete male-specific development in gonads and germ cells. These results suggest that BmdsxM can induce male development in germ cells and internal genital organs, while BmdsxF inhibits BmdsxM activity and represses male differentiation. To investigate whether MASC directly controls male-specific splicing of Bmdsx and identify RNAs that form complexes with MASC in testes, we performed RNA immunoprecipitation (RIP) using an anti-MASC antibody. We found that MASC formed a complex with Bmdsx-AS1 lncRNA, which is a testis-specific factor involved in the male-specific splicing of Bmdsx pre-mRNA.
Conclusions
Combined, our findings suggest that Masc induces male differentiation in gonads and germ cells by interacting with Bmdsx-AS1 lncRNA and enhancing the production of BmdsxM. Unlike Drosophila dsx, BmdsxM was able to induce spermatogenesis in genetically female (ZW) germ cells. To our knowledge, this is the first report indicating the role of dsx in germ cell sexual development differs among insect species.
Clinico-pathologic determinants of non-e-curative outcomes following en-bloc endoscopic submucosal dissection in patients with early gastric neoplasia
Authors: Embaye Kidane Siele , Zhang Chao , Ghebrehiwet Matiwos Araya , Wang Zhihao , Zhang Fengdi , Liu Liwei , Qin Shenghui , Qin Lingzhi , Wang Jun , Wang Xi
Published: June 2020

Background:
Endoscopic submucosal dissection (ESD) is gaining enormous popularity in the treatment of early gastric cancers (EGCs) across many institutions in the world. However, appropriate selection of patients for endoscopic resection is crucial to sufficiently mitigate non-e-curative (NEC) resection. This study aims at identifying the various clinico-pathologic factors that independently predict the depth of submucosal invasion and NEC resection following ESD in patients with EGCs.
Methods:
Multiple logistic regression analysis was applied to investigate factors that independently predict the level of submucosal invasion and NEC resection in patients with early gastric neoplasia. Statistical Packages for the Social Sciences version 23 was used for analysis.
Results:
A total of 162 EGCs underwent en-bloc ESD for which the rate of complete resection and non-e-curative outcomes were 95% and 22.2%, correspondingly. Multivariate analysis depicted that tumor location in the upper two third of stomach (odds ratio [OR] 5.46, confidence interval [CI] 95%, 1.65–18.12, p = 0.006), tumor size > 2 cm (OR 7.63, CI 95%, 2.29–25.42, p = 0.001), histologically undifferentiated tumor (OR 15.54, CI 95%, 1.65-146.22, p = 0.001), and tumors with 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc (OR 9.77, CI 95%, 1.23–77.65, p = 0.031) were all independent predictors of NEC resection for early gastric tumors. Additionally, location in the upper two third of stomach (OR 8.88, CI 95%, 2.90-27.17, p < 0.001), ulcerated lesions (OR 3.70, CI 95%, 1.15–11.90, p = 0.028), lesions with > 2 cm (OR 2.94, CI 95%, 1.08–8.02, p = 0.036) and those with poor differentiation (OR 6.51, CI 95%, 2.23–18.98, p = 0.001) were found to have significant association with submucosal invasion.
Conclusions:
Tumors located in the upper two third of stomach having larger size (> 2 cm), poor histo-differentiation and a gross type of 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc are significantly associated with a risk of NEC after ESD procedure. Thus, early gastric tumors displaying these features need to be handled carefully during endoscopic resection. Our findings may provide some insights about the factors that determine non-curability outcomes in patients with EGC in relation to ESD procedure.
ECG-signal multi-classification model based on squeeze-and-excitation residual neural networks
Authors: Park Junsang , Kim Jinkook , Jung Sunghoon , Gil Yeongjoon , Choi Jong-Il , Son HoSung
Published: June 2020

Background
Accurate electrocardiogram (ECG) interpretation is crucial in the clinical ECG workflow because it is most likely associated with a disease that can cause major problems in the body. In this study, we developed an ECG-signal multi-classification model using deep learning.
Methods
We used a squeeze-and-excitation residual network (SE-ResNet), which is used for efficient image classification. Experiments were performed for seven different types of lead-II ECG data obtained from the Korea University Anam Hospital in South Korea. These seven types are normal sinus rhythm, atrial fibrillation, atrial flutter, sinus bradycardia, sinus tachycardia, premature ventricular contraction and first degree atrioventricular block. We compared SE-ResNet with a residual network (ResNet), as a baseline model.
Results
The SE-ResNet classifier with 152 layers achieved F1 scores of 97.05% for the seven-class classifications. Our model surpassed the baseline model, ResNet, by + 1.40% for the seven-class classifications.
Conclusion
For ECG-signal multi-classification, considering the F1 scores SE-ResNet might be better than the ResNet baseline model.
The impact of COL1A1 and COL6A1 expressions on hypospadias and penile curvature severity
Authors: Yuri Prahara , Gunadi . , Lestari Rahmadani Puji , Fardilla Firly Putri , Setyaningsih Wiwit Ananda Wahyu , Arfian Nur , Dachlan Ishandono
Published: June 2020

Background: Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penile, i.e. chordee. Abnormality of dartos tissue has been suggested as the pathophysiology of the chordee. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expressions of collagen 1 (COL1A1) and COL6A1 in hypospadias patients and associated them with the severity of penile curvature.Methods: We involved 60 children <18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 control in our institution from 2017 – 2020. The expressions of COL1A1 and COL6A1 from dartos tissue were determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (<30 degree), moderate (30-60 degree), and severe (>60 degree). Results: qPCR showed that the COL1A1 and COL6A1 expressions were significantly downregulated in distal (0.88 (0.38-2.53) and 0.54 (0.16-4.35), respectively) and proximal 0.76 (0.33-2.57) and 0.57 (0.18-1.38), respectively) hypospadias groups compared to controls (1.85 (0.24-4.61) and 0.93 (0.17-4.06), respectively) with p-value of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expressions (r=0.458, p<0.0001). Interestingly, the COL1A1 and COL6A1 was also significantly downregulated in the moderate and severe compared to the mild chordee groups with p-value of 0.003 and 0.037, respectively.Conclusions: Aberrant COL1A1 and COL6A1 expressions might affect the abnormality of dartos tissue and penile curvature severity in hypospadias patients.
Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features
Authors: Wang Jingxian , Zheng Peiyan , Huang Zhifeng , Huang Huimin , Xue Mingshan , Liao Chenxi , Zhong Nanshan , Sun Baoqing
Published: June 2020

Background Some patients with Interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. Furthermore, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. Methods 64 patients with IPAF and 50 healthy people served as normal controls. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (9), improvement group (13), and stable group (14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut off value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. The expression differences of these biomarkers and their correlation with the severity of the disease were analyzed. Results Compared with healthy controls, serum SP-A and KL-6 levels in IPAF patients increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and were negatively correlated with DLCO (SP-A: rS = -0.323, p = 0.018; KL-6: rS = -0.348, p = 0.0011). In the patients with progressive disease, the posttreatment serum SP-A and KL-6 levels increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In the patients showing improvement, the levels decreased significantly SP-A (p = 0.007) and KL-6 (p = 0.002). Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001).Conclusions Serum SP-A and KL-6 offers high sensitivity and specificity for the diagnosis of IPAF. The decrease of serum SP-A and / or KL-6 levels in patients with IPAF is related to the improvement of pulmonary function. SP-A and KL-6 may be important biomarkers to evaluate the prognosis of patients with IPAF.
Facilitators and barriers to self-monitoring of blood glucose (SMBG) in diabetic patients visiting family medicine clinics at Akuh. 
Authors: Brohi Asif Hakim , Hakim Arsalan , Khan Muhammad , Malik Ehsanullah , Mugheri Delijan , Shaikh Fozia , Abbas Waseem , Baloch Nadeem , Ashraf Zehra , Mangi Altaf Ali , Lashari Saika
Published: June 2020

BACKGROUND: To determine factors that facilitate and are barriers to self-monitoring of blood glucose in type 2 diabetic patients visiting family medicine clinics at a tertiary care teaching hospital Karachi Pakistan. METHODS: Approximately 255 patients were consecutively recruited from the clinics during April 2018 to May 2019 at Family Medicine outpatient clinics at the Aga Khan University Hospital. Data on socio-demographic status, facilitators and barriers to SMBG were extracted through a questionnaire, after obtaining an informed written consent. Data was entered and analyzed in SPSS version 19.RESULTS: Among study participants 47.5% were above 50 years and 51.4% were males. About 30.2% of the participants were practicing SMBG at least once a month and 26% were practicing it daily. Fear of complications was the biggest facilitator (80.1%) and being expensive (51.4%) was barrier for SMBG. Over half of the SMBG practicing participants (59.7%) were diagnosed with diabetes for more than 05 years (p: 0.63). CONCLUSION: Assessment of blood glucose is a critical component of diabetes treatment and management. It can motivate patients to become active participants in their own care. Health care providers should communicate and educate the patients about the advantages of SMBG.
Yixintongmai Inhibits Proliferation, Migration and Promotes Apoptosis of Vascular Smooth Muscle Cells Cultured with High Glucose
Authors: Guo JingJing , Zhao Di , Dong Pingshuan
Published: June 2020

Background: This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. Methods: VSMCs of the thoracic aorta from 5–8 weeks male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The effects of yixintongmai on proliferation, migration, and apoptosis of VSMCs cultured with high glucose were evaluated. The concentration of yixintongmai powder at 360 μg/ml was chosen for this study according to pre-experimental results. Results: Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P<0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P<0.001) and the expression of PCNA (0.74 ± 0.08 folds, P<0.001) as compared with high glucose. Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P<0.001; scratch wound assay: 2.69 ± 0.22 folds, P<0.001) and the expression of MMP-9 (0.87 ± 0.03 folds, P<0.001) as compared with high glucose. Yixintongmai promoted the apoptosis of VSMCs (0.36 ± 0.12 folds, P<0.001) and inhibited the expression of bcl-2 (0.83 ± 0.07 folds, P<0.01) as compared with high glucose. Yixintongmai inhibited ROS generation (0.58 ± 0.01 folds, P<0.001) and the expression of NF-κB (0.71 ± 0.07 folds, P<0.001) of VSMCs as compared with high glucose. Conclusions: Yixintongmai inhibits the proliferation, migration and promotes the apoptosis of VSMCs cultured with high glucose, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.
Root-associated endophytic bacterial community composition and structure of three medicinal licorices and their changes with the growing year
Authors: Dang Hanli , Zhang Tao , Li Guifang , Mu Yudi , Lv Xinhua , Wang Zhongke , Zhuang Li
Published: June 2020

Background
The dried roots and rhizomes of medicinal licorices are widely used worldwide as a traditional medicinal herb, the activities of which are attributed to a variety of effective components that can be extracted from licorice root. Endophytes and plants form a symbiotic relationship, which is an important source of host secondary metabolites.
Results
In this study, we used high-throughput sequencing technology and high-performance liquid chromatography to explore the composition and structure of the endophytic bacterial community and the content of effective components (glycyrrhizic acid, liquiritin and total flavonoids) in different varieties of medicinal licorices (Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L.and Glycyrrhiza inflata Batal.) and in different planting years (1–3 years). Our results showed that the contents of the effective components in the roots of medicinal licorices were not affected by the variety, but were significantly affected by the growing year (1–3) (P < 0.05), and with a trend of stable increase in the contents observed with each growing year. In 27 samples, 73,316 effective sequences with an average length of 372 nucleotides (nt) were obtained after quality control, and 2,432 effective operational taxonomic units (OTUs) were obtained at 97% identity. The phylum Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes, and the genera unified-Rhizobiaceae, Pseudomonas, Novosphingobium, and Pantoea were significantly dominant in the 27 samples. Distance-based redundancy analysis (db-RDA) showed that the content of total flavonoids explained the differences in composition and distribution of endophytic bacterial communities in roots of cultivated medicinal liquorices to the greatest extent. Total soil salt was the most important factor that significantly affected the endophytic bacterial community in soil factors, followed by ammonium nitrogen and nitrate nitrogen. Among the leaf nutrition factors, leaf water content had the most significant effect on the endophytic bacterial community, followed by total phosphorus and total potassium.
Conclusions
This study not only provides information on the composition and distribution of endophytic bacteria in the roots of medicinal licorices, but also reveals the influence of abiotic factors on the community structure of endophytic bacteria and effective components, which provides a reference for improving the quality of licorice.
Prenatal Diagnosis of Fetal Skeletal Dysplasia Using 3-Dimensional Computed Tomography: A Prospective Study
Authors: Waratani Miyoko , Ito Fumitake , Tanaka Yukiko , Mabuchi Aki , Mori Taisuke , Kitawaki Jo
Published: June 2020

Background
Fetal skeletal dysplasia (FSD) comprises a complex group of systemic bone and cartilage disorders. Many FSD phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. The condition is typically diagnosed using sonography; however, three-dimensional computed tomography (3D-CT) also aids in making a prenatal diagnosis. This study aimed to examine the efficacy of 3D-CT in the prenatal diagnosis of FSD by comparing the diagnostic accuracy of fetal sonography and 3D-CT.
Methods
On suspicion of FSD based on ultrasound examination, we performed 3D-CT prenatally to confirm this diagnosis. In order to minimize exposure of the fetuses to radiation without compromising image quality, we used predetermined 3D-CT settings for volume acquisition.
Results
Sixteen fetuses were suspected to have skeletal dysplasia based on ultrasonography findings. Of these, 15 were diagnosed with FSD using 3D-CT. All 15 fetuses diagnosed with skeletal dysplasia prenatally were confirmed postnatally to have the condition. The definitive postnatal diagnosis (campomelic dysplasia) differed from the prenatal diagnosis (osteogenesis imperfecta) in only one infant. Fourteen cases (93.3%) were diagnosed by an accurate classification. Five infants had lethal skeletal dysplasia; one died in utero, and four died as neonates. We determined the appropriate delivery method for each infant based on the prenatal diagnosis.
Conclusions
3D-CT is a valuable tool to augment ultrasound examination for the diagnosis of FSD because it can provide a more definitive diagnosis of the type of dysplasia, enabling better planning for resuscitation of the infant after birth.
Trial registration:
University Hospital Medical Information Network (UMIN) Center trial registration number is UMIN000034744. Registered 1 October, 2018 – Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=Roooo39610.
Spontaneous Oesophageal Rupture of The Right Wall After Oral Administration of Sulfate Solution: An Unusual Case Report
Authors: Xu Hao , Huang Ning , Li Lin , Ma Pingchuan , Huang Dongping , He Chiyi
Published: June 2020

Background: Patients with gastrointestinal stenosis, Barrett's oesophagus, and vomiting during endoscopic preconditioning or after general anaesthesia may develop spontaneous oesophageal rupture in the literature. However, we found an unusual case in which oral sulfate solution triggered oesophageal perforation. Additionally, the oesophageal chasm uncommonly presented at the right wall, while most ruptures are located in the left wall of the oesophagus, and the unexplained and rapidly progressive right-sided pleural effusion in this patient could be associated with this entity. To the best of our knowledge, this is the first published case of oesophageal rupture of the right wall after oral administration of sulfate solution in the literature.Case presentation: For this patient, he suffered from acute onset of unbearable epigastric pain and compression pain in the right chest, with dyspnea, chest tightness and palpitation, after severe nausea and vomiting following oral administration of sulfate solution, and findings from imaging and gastroscopy eventually confirmed oesophageal rupture. Anti-infective treatments, pleural drainage, rehydration and total parenteral nutrition were administered immediately; subsequently, we used a total of seven titanium clips to close the oesophageal rupture under gastroscopic guidance. Eventually, he demonstrated good evolution after the operation and was discharged after recovery. Conclusions: This case emphasizes the importance of considering BS when dealing with patients with severe vomiting, acute chest pain, or dyspnea, especially after administration of sulfate solution for bowel cleansing.
Little Akaki River Sediment Enrichment with Heavy Metals, Pollution Load and Potential Ecological Risks in Downstream, Addis Ababa, Ethiopia
Authors: Mekuria Deshu Mamo , Kassegne Alemnew Berhanu Berhanu , Asfaw Seyoum Leta Leta
Published: June 2020

Background: Little Akaki River (LAR) passes through Addis Ababa City, receives inorganic and organic pollutants from various sources. The objective of this study was to investigate the pollution level of LAR by selected heavy metals and evaluate sediment quality using contamination indices.Methods: sediment samples were collected from 10 stations along LAR, processed, digested and heavy metal content was analyzed using ICP-OES. Enrichment factor (EF), geo-accumulation index (Igeo), contamination factor (CF), pollution load index (PLI), ecological risk index (RI) were determined. Comparison was made with standard sediment qualities (SQGs) to evaluate ecological and toxicological implication.Results: the mean concentrations of heavy metals in LAR sediment were: Zn (78.96-235.2 mg / kg); Cr (2.19-440.8 mg / kg); Cd (2.09-4.16 mg / kg) and Pb (30.92-596.4 mg / kg). EF values indicated that LAR sediments were moderate to significant enrichment with Zn and Cr; moderate to very high enrichment with Pb, and very high enrichment in all sampled sites with Cd. Igeo and CF values indicated that the sediments were moderate to very high contamination with toxic Cd and Pb.PLI and hierarchal cluster analysis revealed that highest pollution load occurred at sampling site (S9), in lower course of the river mainly due to anthropogenic metals inputs from industrial wastes, municipal wastewater treatment plant and agrochemical wastes; hence, its quality was deteriorated and depicted polluted site. The decreasing order of PLI in downstream was: (S9) > (S4) > (S8) > (S3)> (S6) > (S10) > (S5) > (S2)> (S7) > (S1). Pearson correlation indicated that Zn and Cd were generated from common sources of pollution. The ecological risk (RI =350.62) suggested that the contaminated LAR sediment can pose considerable ecological risks of pollution.Conclusions: The concentrations of Zn, Cr, Cd and Pb in LAR sediment were surpassed sediment quality guidelines (USEPA) and eco-toxicological guideline limit values of USEPA (TEC) and CMME (ISQGs). Thus, the contaminated sediments can occasionally pose adverse biological effects on sediment dwelling organisms and impairs the quality of river water. Thus, monitoring and addressing sediment contamination becomes necessary to sustain beneficial uses of river water for various development purposes.
C-C Chemokine Receptor Type 5 Links COVID-19, Rheumatoid Arthritis, and Hydroxychloroquine
Authors: HACHIM Mahmood Yaseen , Hachim Ibrahim Y. , Naeem Kashif , Hannawi Haifa , Salmi Issa Al , Hannawi Suad
Published: June 2020

Background: Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to coronavirus disease -19 (COVID-19) and its severe form. On the other side, RA patients have been found not to have an increased risk of COVID19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side Methods: We used the in silico approach to investigate the transcriptomic profile of RA synovium compared to osteoarthritis and healthy controls to identify RA specific molecular pathways shared with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Results: Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted that HCQ might interfere with the COVID-19 infection through its ability to upregulate specific immune cell populations like activated natural killer (NK) cells, besides blocking CCR5 rich immune cell recruitment to the SARS-COV-2 infected lungs Conclusion: Our results might explain some of the reports that showed beneficial effects and indicate the need for proper patients stratification on their immune profile before selecting the therapeutic protocol or clinical trial enrollment. Keyword COVID-19, SARS-COV-2, Hydroxychloroquine, rheumatoid arthritis
Inference of Molecular Subtypes of Uterine Corpus Endometrioid Carcinoma with Different Survival Based on Cancer Hallmarks-associated Long Non-Coding RNAs and Gene Modules
Authors: Lv Nan , Zhao Shuyu , Li Yan , Liu Tianyi , Chu Xiaodan
Published: June 2020

Background: Uterine corpus endometrioid carcinoma (UCEC), a common gynecological malignancy with high incidence, affects the mental and physical health of women. It is increasingly evident that long non-coding RNAs (lncRNAs) have causative roles in cancers including UCEC. However, very little is known about the cancer hallmark-related risks for UCEC based on lncRNAs and genes. Methods: In this study, a computational integrated pipeline was development to evaluate cancer hallmark-related risk for each UCEC patient based on gene and lncRNA expression. Results: Some UCEC-specific cancer hallmark-related genes and lncRNAs were identified. Core modules were extracted from co-expressed UCEC-specific lncRNAs and genes networks for each cancer hallmark. Some core modules showed specific features and functions. Follow a multi-dimensional rank approach and core modules, each UCEC sample was given an integrated cancer hallmark-related risk score. We divided all the UCEC patients to diverse hallmark risk groups including multi-hallmark, media-hallmark and single-hallmark groups and they showed different prognosis. We also identified some key lncRNAs which participated in multiple kinds of cancer hallmarks. These key lncRNAs were associated with some essential pathways such as estrogen receptor signaling. Conclusions: In conclusion, the present study provide novel insights to the classification and treatment of UCEC.
Virtual Screening of Heterocyclic Molecules to Identify Potential SARS-COV2 virus Mpro Protease Inhibitors for Further Medicinal Chemistry design
Authors: Sobeh Mansour , Mrid Reda Ben , Yasri Abdelaziz
Published: June 2020

In this work, we aimed to identify potential SARS-COV2 virus Mpro protease inhibitors using molecular docking. As a validation step of our docking approach, we used 7 known Mpro inhibitors and predicted their binding energies. We found a very good correlation (R = -0.86) between the binding energies and the pIC50 (-LogIC50) values. We then undertook virtual screening of 50753 heterocyclic molecules from the PubChem Database. The screened molecules were first filtered out using Lipinski, Veber and Ghose rules resulting in 21 142 which was submitted to the docking phase. The docked compounds were ranked according to their predicted binding energy to the protease and a threshold of -9.0 Kcal/mol was applied resulting in a set of 2711 hits. These hits were split into different groups according to their chemical class using a rule-based classification approach. The best compound from each of the most populated classes were subjected to binding mode analysis which led to ligand-receptor interaction maps and suggested some medicinal chemistry-oriented modifications to further optimize the potency of the obtained hits. Predicted IC50 of the hit molecules ranged from 0.85 to 0.43 µM against SARS-COV2 virus Mpro protease.
Systemic Elucidate The Potential Bioactive Compounds and Hypoglycemic Mechanism of Polygonum Multiflorum Based on Network Pharmacology
Authors: Song Yunfei , Yang Jianbo , Jing Wenguang , Wang Qi , Liu Yue , Cheng Xianlong , Wei Feng , Ma Shuangcheng
Published: June 2020

Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Finally, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.
Anastomotic Leakage Following Colorectal Cancer Surgery: Comparison Between Conservative and Surgical Treatment
Authors: Ishiyama Yasuhiro , Oneyama Masaki , Tomizawa Yuki , Amiki Manabu , Ito Shingo , Hara Yoshiaki , Narita Kazuhiro , Goto Manabu , Sekikawa Koji , Fujino Shozo , Tachimori Yuji
Published: June 2020

Backgrounds
Anastomotic leakage following colorectal cancer is associated with significant morbidity and mortality. However, whether the choice of the treatment for anastomotic leakage may affect the oncological outcomes is under debate. We evaluated the oncological outcomes after colorectal cancer surgery for anastomotic leakage between conservative and surgical treatment.
Methods
We retrospectively analyzed data for patients with colorectal cancer who underwent curative colectomy from April 2010 to January 2020.
Results
A total 1039 patients underwent surgery colorectal cancer in our hospital. After exclusion, a total of 915 patients underwent a low anastomosis with diverting stoma for colorectal cancer of which 92 (10.0%) anastomotic leakage occurred. After stage Ⅳ and emergency surgery case were excluded, a total of 75 patients were included for the analysis. The surgical treatment group was 25 cases. The conservative treatment group was 50 cases. Early anastomotic leakage was more than in surgical treatment compared to conservative treatment (84% vs 54%, P =0.008). The 5-year overall survival rates and the 5-year disease free survival did not differ significantly between the two groups. The recurrence location of liver metastasis was more than in surgical treatment compared to conservative treatment (20% vs 2 %, P=0.02). On a multivariable analysis, anastomotic leak did not impact overall survival and disease free survival.
Conclusion
We found that the treatment for anastomotic leakage was not depended on increased local, distance recurrence, overall survival, and disease free survival. Our findings may help surgeons determine which AL treatment is most appropriate, when the decision is unclear.
Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin
Authors: Zhou Tieli , Liu Shixing , Fang Renchi , Zhang Ying , Chen Lijiang , Huang Na , Yu Kaihang , Zhou Cui , Cao Jianming
Published: June 2020

Background: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains.Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed.Results: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). And the mechanism of colistin resistance is increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.Conclusions: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.
Catheter-Related Bloodstream Infections in Children with Short Bowel Syndrome: A Single Center Retrospective Study
Authors: Yuan Chenling , Li Xiaolu , Hu Hui , Li Dan , Xiao Yongmei , Wang Yizhong , Zhang Ting
Published: June 2020

Background: Pediatric short bowel syndrome (SBS) is a devastating clinical entity that is usually managed with parenteral nutrition (PN). Catheter-related bloodstream infection (CRBSI) is a serious complication of long-term PN. The aim of this study was to evaluate the incidence and risk factors of CRBSI in SBS children. Methods: Nineteen pediatric patients with SBS were retrospectively recruited from Shanghai Children’s Hospital between August 2015 and December 2019. Clinical data, including demographics, aetiology of SBS, site and type of catheters, duration of PN, comorbidities, and microbiological data regarding CRBSI, were collected and reviewed to assess the CRBSI incidence and associated risk factors. Results: A total of 57 catheter insertions for PN were administered in 19 SBS children. CRBSI was identified in 11 cases among 6 patients during a total catheter days of 1907. The rate of CRBSI was 5.8 per 1000 catheter days. The common manifestations of the SBS children with CRBSI were fever (6/11, 54.5%), lethargy (5/11, 45.4%), stagnation of weight (7/11, 63.6%), and increment of enterostomy fluid (7/11, 63.6%). Potential risk factors for CRBSI included an absence of ileocecal valve (p=0.046), and long duration of PN (p=0.019). The most common microorganism isolated from the blood cultures was Klebsiella pneumoniae (6/11, 54.55%). Conclusions: The rate of CRBSI was 5.8 per 1000 catheter days, and klebsiella pneumoniae was the most common isolated pathogen of CRBSI in the studied SBS children. An absence of ileocecal valve and long duration of PN were potential risk factors of CRBSI.
Axitinib in Combination with Radiotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial
Authors: Yang Kai-Lin , Chi Mau-Shin , Ko Hui-Ling , Huang Yi-Ying , Huang Su-Chen , Lin Yu-Min , Chi Kwan-Hwa
Published: June 2020

Background: Axitinib is a selective vascular endothelial growth factor receptors 1–3 inhibitor approved for second-line treatment of advanced renal cell carcinoma. In a randomized, placebo-controlled phase II trial for patients with locally advanced or metastatic hepatocellular carcinoma (HCC), axitinib improved progression-free survival and showed overall response rate of 9.7%. This phase I study aimed at evaluating maximum tolerated dose (MTD) of axitinib in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC).Methods: This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT.Results: Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months.Conclusions: Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort.Trial registration: ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461
Knowledge, Attitude, and Practice and Associated Factors towards COVID-19 among College Students in Amhara Region, Ethiopia; A Cross-Sectional Study
Authors: Tadesse Abay W. , Melese Negesse , Eshetie Sisay , Chane Mulugeta , Ali Amhed
Published: June 2020

Background: Ethiopia has taken unprecedented preventive measures like closure of higher education institutions to halt the spread of COVID-19. However, still, there is scarce information regarding the knowledge, attitude, and practice (KAP) of students towards COVID-19 pandemic. Thus, this study aimed to assess the KAP and associated factors of preventive measures against COVID 19 among students.Methods: A cross-sectional study design was conducted among 422 students. The sample was proportionally allocated into the randomly selected four colleges and the students were recruited using a systematic random sampling technique. Variables with p-value < 0.25 in the bivariate logistic regression analysis were entered into the multivariable logistic regression model.Results: this study involved 408 students with response rate of 96.6%. The level of good knowledge, positive attitude and good practice were 69.6%, 56.6% and 65% respectively. After adjusting for covariates; being in the late adolescent age group (16-20), living with > 5 family size, and being single were predictors of knowledge level. Besides, being single, learning Diploma (TVET) level trainings, and being year-two students were predictors of attitude levels. Similarly, urban residence, being regular students, and being year-one students were the independent predictors of practice level of students.Conclusions: The national and local governments should develop effective and inclusive prevention strategies to address students who are at home due to COVID-19 pandemic.
The Expression of TLR2 and TLR4 in the Kidneys and Heart of Mice Infected with Acanthamoeba Spp.
Authors: Kot Karolina , Kosik-Bogacka Danuta Izabela , Wojtkowiak-Giera Agnieszka , Kolasa-Wołosiuk Agnieszka , Łanocha-Arendarczyk Natalia
Published: June 2020

Background: Acanthamoeba spp. are cosmopolitan protozoa that cause infections in the brain, as well as extracerebral infections in the cornea, lungs and skin. Little is known about the mechanisms of the immunological response to these parasites in organs which are not their main biotope. Therefore, the purpose of this study was to determine the expression of TLR2 and TLR4 in the kidneys and heart of Acanthamoeba spp. infected mice, with respect to the host’s immunological status. Results: In the kidneys, we observed a higher expression of TLR2 in immunosuppressed mice at 24 days post Acanthamoeba spp. infection (dpi) compared to the uninfected mice. There were no statistically significant differences in TLR4 expression in the kidneys between the immunocompetent and immunosuppressed mice, both of infected and uninfected mice. In the heart, we observed a difference in TLR2 expression in immunocompetent mice at 24 dpi compared to immunocompetent mice at 8 dpi. The immunocompetent Acanthamoeba spp. infected mice had higher TLR4 expression at 8 dpi compared to the immunocompetent uninfected mice. Conclusions: Our results indicate that TLR2 is involved in response to Acanthamoeba spp. infection in the kidneys, whereas in the heart, both studied TLRs are involved.
Structural, Optical, Magnetic and Photocatalytic Properties of Sr2Nb2O7-Nb2O5-SrCO3 Nanocomposite Synthesized by Solvothermal Route
Authors: nazarlou Ziba davtalab , Kafi-Ahmadi Leila , khademinia shahin
Published: June 2020

Sr2Nb2O7 nanocomposites were prepared by a low cost ultrasonic assisted solvothermal method between Sr(NO3)2 and Nb2O5 at stoichiometric Sr:Nb molar ratio. The synthesized nanomaterials were characterized by X-ray powder diffraction (XRPD) technique. Rietveld analysis showed that the obtained materials were crystallized well in the orthorhombic crystal structure with the space group Cmc21. The morphologies of the synthesized materials were studied by field emission scanning electron microscope (FESEM). Strong light absorption in the ultraviolet light region at about 320 nm was observed for the synthesized nanocomposites by Ultraviolet-visible spectra. Vibrating-sample magnetometer (VSM) analysis showed that the as-synthesized nanomaterials had ferromagnetic property. Photocatalytic performance of the synthesized nanocomposites was investigated for the degradation of Malachite Green (MG) water pollutant in aqueous solution under visible light condition. The light source was a white color fluorescent lamp with the light power of 40 W and the light intensity of 920 lm/m2 (1.34 W/m2). Design expert software was used to find the optimum conditions. The optimum conditions were found as 0.61 mL H2O2, 40 mg catalyst, and 60 min. The as prepared MG solution volume and concentration were 80 mL and 50 ppm, respectively, to achieve the optimum conditions. The kinetic study showed that the photodegradation process followed a first order reaction model.
Effects of Reinforcement Ratios and Sintering Temperatures on the Mechanical Properties of Titanium Nitride/Nickel Composites
Authors: Chen Yi-Cheng , Ou Shih-Fu
Published: June 2020

In this study, powder metallurgy was used to fabricate titanium nitride/nickel metal-matrix composites. First, Ti and Ni powders with weight ratios of 20:80, 50:50, and 80:20 were dry mixed for 24 h. After cold isostatic pressing, the green compacts were soaked in a water-based hot forging lubricant and sintered at 850, 950, and 1050°C for 1.5 h in an air atmosphere. The effects of the amount of titanium powder and the sintering temperature on the mechanical properties (hardness, wear resistance, and compressive strength) of the composites were investigated. The results indicated that titanium gradually transformed into titanium nitride near the surface after sintering due to the carbothermal reduction reaction; this transformation was observed to significantly increase the hardness. In addition, a titanium oxide film was observed to form between the titanium particles and the nickel matrix. The optimum sintering temperature of 950°C provides the composites with titanium-nickel weight ratios of 20:80 and 50:50, the latter of which exhibited the best mechanical properties (wear resistance and compressive strength). Furthermore, increasing the titanium content to 80% in the composite increased the hardness; however, the wear resistance and compressive strength were observed to reduce.