bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic activity and brine shrimp lethality of venom from the large brown spitting cobra (Naja ashei) and its neutralization by antivenom
Authors: Okumu Mitchel Otieno , Mbaria James Mucunu , Gikunju Joseph Kangangi , Mbuthia Paul Gichohi , Madadi Vincent Odongo , Ochola Francis Okumu 
Published: June 2020

Abstract
Objective: Naja ashei is a snake of medical importance in Kenya, Ethiopia, Somalia, Uganda, and Tanzania. Little is known about the enzymatic (snake venom phospholipases A2; svPLA2’s) and toxic (lethal) activities of Naja ashei venom and crucially, the safety and capacity of available antivenom to neutralize these effects. This study aimed to determine the enzymatic and toxic activities of Naja ashei venom and the capacity of Indian and Mexican manufactured antivenoms to neutralize these effects. The protein content of the venom and the test antivenoms were also evaluated. A 12-point log concentration-response curve (0.5-22.5 µg/mL) was generated on an agarose-egg yolk model to predict the svPLA2 activity of the venom. The toxicity profiles of the venom and antivenoms were evaluated in the brine shrimp lethality assay. Lowry’s method was used for protein estimation. Results: Low and intermediate concentrations of the venom exhibited similar svPLA2 activities. The same was true for concentrations >15 µg/mL. Intermediate and high doses of the venom exhibited similar mortalities in brine shrimp and test antivenoms were generally non-toxic but poorly neutralized svPLA2 activity. Mexican manufactured antivenom had lower protein content but neutralized venom-induced brine shrimp lethality much more effectively than Indian manufactured antivenom.
Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2
Authors: chen hongzhi , Tang Lingli , Yu Xinling , Zhou Jie , Chang Yunfeng , Wu Xiang 
Published: June 2020

Abstract
Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods : The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results : A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike 315-324 , Spike 333-338 , Spike 648-663 , Spike 1064-1079 ) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly 496 , Glu 498 , Pro 499 , Thr 500 , Leu 1141 , Gln 1142 , Pro 1143 , Glu 1144 , Leu 1145 , Asp 1146 ) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC classⅠand MHC classⅡ molecules respectively. The peptides (Nucleocapsid 66-75 , Nucleocapsid 104-112 ) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions : B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.
Bacillus subtilis spore vaccines displaying protective antigen induce functional antibodies and protective potency
Authors: Oh Yeonsu , Kim Jung Ae , Kim Chang-Hwan , Choi Soo-Keun , Pan Jae-Gu 
Published: June 2020

Abstract
Background: Bacillus anthracis is the causative agent of anthrax, a disease of both humans and various animal species, and can be used as a bioterror agent. Effective vaccines are available, but those could benefit from improvements, including increasing the immunity duration, reducing the shot frequency and adverse reactions. In addition, more sophisticated antigen delivery and potentiation systems are urgently required. The protective antigen (PA), one of three major virulence factors associated with anthrax was displayed on the surface of Bacillus subtilis spores, which is a vaccine production host and delivery vector with several advantages such as a low production cost, straightforward administration as it is safe for human consumption and the particulate adjuvanticity. Mice were immunized orally (PO), intranasally (IN), sublingually (SL) or intraperitoneally (IP) with the PA displaying probiotic spore vaccine. Clinical observation, serological analysis and challenge experiment were conducted to investigate the safety and efficacy of the vaccine. Results: A/J mice immunized with the PA spore vaccine via PO, IN, SL, and IP were observed to have increased levels of active antibody titer, isotype profiles and toxin neutralizing antibody in sera, and IgA in saliva. The immunized mice were demonstrated to raise protective immunity against the challenge with lethal B. anthracis spores. Conclusions: In this study, we developed a B. subtilis spore vaccine that displays the PA on its surface and showed that the PA-displaying spore vaccine was able to confer active immunity to a murine model based on the results of antibody isotype titration, mucosal antibody identification, and a lethal challenge experiment.
Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case-control study analyzing respiratory biomechanics and diagnostic accuracy
Authors: Tuza Fábio Augusto d´Alegria , de Sá Paula Morisco , Castro Hermano , Lopes Agnaldo José , de Melo Pedro Lopes 
Published: June 2020

Abstract
Background Fractional-order (FrOr) models have a high potential to improve pulmonary science. These models could be useful for biomechanical studies and diagnostic purposes, offering accurate models with an improved ability to describe nature. This paper evaluates the performance of the Forced Oscillation (FO) associated with integer (InOr) and FrOr models in the analysis of respiratory alterations in work-related asthma (WRA). Methods Sixty-two individuals were evaluated: 31 healthy and 31 with WRA with mild obstruction. Patients were analyzed pre and post bronchodilation. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). To evaluate how well do the studied models correspond to observed data, we analyzed the mean square root of the sum (MSEt) and the relative distance (Rd) of the estimated model values to the measured resistance and reactance measured values. Results and discussion Initially, the use of InOr and FrOr models increased our understanding of the WRA physiopathology, showing increased peripheral resistance, damping, and hysteresivity. The FrOr model (AUC=0.970) outperformed standard FO (AUC=0.929), as well as InOr modeling (AUC=0.838) in the diagnosis of respiratory changes, achieving high accuracy. FrOr improved the curve fitting (MSEt=0.156±0.340; Rd=3.026±1.072) in comparison with the InOr model (MSEt=0.367±0.991; Rd=3.363±1.098). Finally, we demonstrated that the bronchodilator use increased dynamic compliance, as well as reduced damping and peripheral resistance. Conclusions Taken together, these results show clear evidence of the utility of FO associated with fractional-order modeling in patients with WRA, improving our knowledge of the biomechanical abnormalities and the diagnostic accuracy in this disease.
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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.&nbsp;
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

Abstract
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.