bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 in Northeast Bosnia and Herzegovina and patients length of hospitalization
Authors: Trnacevic Alma , Mujkanovic Amer , Al-Salloum Noura , Sakusic Amra , Trnacevic Emir , Jusufovic Emir , Hukic Fatima , Jahic Rahima , Stratton Richard 
Published: June 2020

Abstract
Background Since outbreak of COVID-19 pandemic clinical data from various parts of the world have been reported, until now there has been no provide data from Bosnia and Herzegovina (B&H) about COVID-19. Aim was to report on the first cohort of patients from B&H and to analyze clinical factors of COVID-19 patients that influence the length of hospitalization. Methods Retrospective cohort study conducted at UKC Tuzla. The study included 25 COVID-19 positive patients that were hospitalized between March 28th and April 27th 2020. The LOH was measured from the time of admission to discharge. Hospitalization greater than 10 days was considered as prolonged. Factors analyzed induced age, BMI, comorbidities, serum creatinine and oxygen saturation upon admission.Results The mean age was 52.92±19.15 years and BMI 28.80±4.22. LOH for patients with normal BMI was 9±SE2.646 days (CI 95% 3.814-14.816) vs 14.182 ±SE .937 (CI 95% 12.346-16.018; p<0.05) for ≥25 BMI. Patients without underlying diseases had a LOH of 11.70 ±SE1.075 (CI 95% 9.592-13.808), while those with comorbidities 14.8 ±SE1.303 (CI95% 12.247-17.353; p<0.05). Conclusion LOH varied among COVID-19 patients and was prolonged when clinical characteristics such as elevated BMI, comorbidities, elevated creatinine and low oxygen saturation levels were taken into consideration. Furthermore, risk factors for COVID-19 patients in B&H do not deviate from data reported in other countries.
Metagenomic discovery and functional validation of L-asparaginases with anti-leukemic effect from the Caspian Sea
Authors: Sobat Motahareh , asad sedigheh , Kabiri Mahboubeh , Mehrshad Maliheh 
Published: June 2020

Abstract
Background
L-asparaginase has been used for the treatment of acute lymphoblastic leukemia (ALL) for more than 30 years. However, efforts continued to find new enzymes with more desirable properties due to the immunogenicity, short half-life, rapid clearance and L-glutaminase side activity of the existing commercial enzymes. Screening for novel L-asparaginases in prokaryotes as a promising resource has been mainly hampered by the cultivation/expression bottleneck.
Results
By screening 27000 publicly available prokaryotic genomes, we recovered ca. 6300 type I and ca. 5200 type II putative L-asparaginase in 36 and 42 bacterial phyla respectively highlighting the vast potential of prokaryotes for L-asparaginase activity. Caspian water with similar salt composition to the human serum was targeted for in-silico screening of L-asparaginase. We screened ca. three million predicted Open Reading Frames of the assembled Caspian Sea metagenomes. In-silico screening resulted in 87 putative L-asparaginase genes from the Caspian Sea datasets. The L-asparagine hydrolysis was experimentally confirmed by cloning three selected genes (1092, 1218 and 1011 bp) in E. coli. Catalytic parameters of the purified enzymes including Km, Vmax and catalytic efficiency were determined to be among the most desirable reported values of microbial L-asparaginases. Two of the recombinant enzymes represented remarkable anti-proliferative activity (IC50 less than 1 IU/ml) against leukemia cell line Jurkat while no cytotoxic effect on human erythrocytes or human umbilical vein endothelial cells was detected.
Conclusions
Similar salinity and ionic concentration of the Caspian water samples to the human serum highlights the secretory L-asparaginases recovered from these metagenomes as potential treatment agents.
Shotgun metagenomics reveals significant gut microbiome features in different grades of acute pancreatitis
Authors: Yu Shanshan , Xiong Yangyang , Fu Yangyang , Chen Guorong , Zhu Huadong , Mo Xun , Xu Jun , Wu Dong 
Published: June 2020

Abstract
Background: Acute pancreatitis (AP) has a broad spectrum of severity and is associated with considerable morbidity and mortality. We aimed to evaluate the composition and functional effects of gut microbiota in different grades of AP severity. Results: Gut microbiota in AP patients was characterized by decreased species richness. The most representative gut microbiota in mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) was Streptococcus, Escherichia-coli, and Enterococcus, respectively. Each of the three AP-associated genera could differentiate AP from healthy control population. Representative pathways associated with the glutathione metabolism, lipopolysaccharide biosynthesis, and amino acid metabolism (valine, leucine and isoleucine degradation) were enriched in MAP, MSAP, and SAP, respectively. Conclusions: Our findings indicate that in patients with AP, the gut microbiome composition and function are correlated with different severity of AP from a whole-genome perspective, and new changes are observed.
A multidisciplinary experimental study on the effects of breeders diet on newborn seahorses (Hippocampus guttulatus)
Authors: Planas Miquel , Olivotto Ike , González María Jesús , Laurá Rosaria , Zarantoniello Matteo 
Published: June 2020

Abstract
The global trade in seahorses is increasing and new rearing techniques are currently available for a few species. One of the main bottlenecks in seahorse production is reproduction success, which is dependent upon the administration of high quality diets to breeders. However, very little is known about the most adequate diets, on how they should be administered and on how they might affect newborn performance. In this study, three homogeneous groups of adult seahorses Hippocampus guttulatus were maintained in captivity. Each group was fed on one of the following diets since the onset of the breeding period: Unenriched adult Artemia (Diet A), unenriched adult Artemia and mysidaceans (Diet AM) and mysidaceans (Diet M). As a positive control we used a wild pregnant male. The mixed diet AM provided the highest overall breeding success and reasonable fatty acid profiles, and better resembled newborn from a wild male. The use of only mysidaceans (Diet M) provided the worse results in spite of the high DHA content. Significant differences were observed in newborn characteristics and fatty acid profiles among dietary groups and along the breeding season, especially in total n-3 HUFA and DHA. Monospecific diets including Artemia or mysidaceans very likely suffered nutritional deficiencies, which were reflected in morphological alterations of the muscle tissue (diet A) or abnormal early mortalities in newborn (diet M). Three progressive stages were identified along the whole breeding period: Initial mixed capital-income period (100 – 120 days since the onset of the breeding period), followed by an inflexion period (short transitional stage - income sources), and finally a long period characterized by the use of income sources and the progressive exhaustion of body reserves. Special attention should be deserved to the progressive changes in fatty acid profiles along the breeding season, resulting in a decrease in newborn performance. Considering the time required for a diet to be reflected in newborn, we recommend Hippocampus guttulatus breeders to be fed on a high quality diet for at least three months prior the breeding period.
Machine Learning and Statistical Approaches for Classification of Risk of Coronary Artery Disease using Plasma Cytokines.
Authors: Saharan Seema Singh , Nagar Pankaj , Creasy Kate Townsend , Stock Eveline O. , Feng James , Malloy Mary J. , Kane John P. 
Published: June 2020

Abstract
Background As per the 2017 WHO fact sheet, Coronary Artery Disease (CAD) is the primary cause of death in the world, and accounts for 31% of total fatalities. The unprecedented 17.6 million deaths caused by CAD in 2016 underscores the urgent need to facilitate proactive and accelerated pre-emptive diagnosis. The current research took an innovative approach to implement K Nearest Neighbor (k-NN) and ensemble Random Forest Machine Learning algorithms to achieve a targeted “At Risk” Coronary Artery Disease (CAD) classification. To ensure better generalizability mechanisms like k-fold cross validation, hyperparameter tuning and statistical significance (p<.05) were employed. The classification is also unique from the aspect of incorporating 35 cytokines as biomarkers within the predictive feature space of Machine Learning algorithms.Results A total of seven classifiers were developed, with four built using 35 cytokine predictive features and three built using 9 cytokines statistically significant (p<.05) across CAD versus Control groups determined by independent two sample t tests. The best prediction accuracy of 100% was achieved by Random Forest ensemble using nine significant cytokines. Significant cytokines were selected to decrease the noise level of the data, allowing for better classification. Additionally, from the bio-medical perspective, it was enlightening to empirically observe the interplay of the cytokines. Compared to Controls, moderately correlated (correlation coefficient r=.5) cytokines “IL1-β”, “IL-10” were both significant and down regulated in the CAD group. Both cytokines were primarily responsible for the Random forest generated 100% classification. In conjunction with Machine Learning (ML) algorithms, the traditional statistical techniques like correlation and t tests were leveraged to obtain insights that brought forth a role for cytokines in the investigation of CAD risk.Conclusions Presently, as large-scale efforts are gaining momentum to enable early detection of individuals at risk for CAD by the application of novel and powerful ML algorithms, detection can be further improved by incorporating additional biomarkers. Investigation of emerging role of cytokines in CAD can materially enhance the detection of risk and the discovery of mechanisms of disease that can lead to new therapeutic approaches.
Psychometric assessment of translated Urdu version of WHOQOL-HIV BREF among patients living with HIV
Authors: Ahmed Ali , Saqlain Muhammad , Akhtar Nasim , Hashmi Furqan K , Blebil Ali , Dujaili Juman , Umair Malik M , Bukhsh Allah 
Published: June 2020

Abstract
ObjectiveThe Low Middle Income Countries (LMIC) like Pakistan are facing an escalation in the number of HIV cases, approximately more than 180,000 people are currently living with HIV/AIDS (PLWHA). Currently, no HIV specific Health Related Quality of Life (HRQoL) tool is validated in Pakistan; therefore, the current analysis was aimed at translating and examining the psychometric properties of the Urdu version of WHOQOL HIV BREF among HIV patients of Pakistan.MethodsThe standard forward-backwards translation technique was used for Urdu translation of the instrument. Based on the principle of 5 subjects minimally for each item, a sample of 182 patients were recruited by employing a universal random sampling technique. Data were analysed to measure reliability, internal consistency, known-group, multivariable linear regression and construct validity. Results High internal consistency 0.93 (Cronbach alpha) was found for all WHOQOL HIV Bref facets. The test-retest reliability analysis demonstrated a statistically significant Interclass Correlation Coefficient (ICC) ranged from 0.88 – 0.98 (p < 0.001). In known group validity, lower CD-4 lymphocytes count was significantly related to poor scores for all six domains (p < 0.001). Similarly, symptomatic subjects had significantly lower scores compared to asymptomatic subjects on the physical, psychological, social relationship and independence domains (p < 0.05). Results also revealed a statistically significant positive correlation of all six domains with CD4 count (p < 0.001), exhibiting patients with higher CD-4 lymphocytes count will have higher mean scores of all six domains. Factor analysis revealed 5 domains, including Physical health, Psychological health, Social relationship, Environmental, and Spiritual health. When all domains were assessed together via Multivariable linear regression analysis; only physical, psychological health and environment health domains were found significantly associated with higher CD-4 lymphocytes count (Beta = 0.121, p < 0.001, Beta = 0.103, p = 0.002, and Beta = 0.032, p = 0.032).ConclusionFindings suggested that the Urdu version of WHOQOL HIV Bref is a psychometrically valid tool for measuring HRQoL.
Chronic oral administration of P. gingivalis induces microglial activation and degeneration of dopaminergic neurons possibly through increase in gut permeability and peripheral IL-17A in LRRK2 R1441G mice
Authors: Feng Yu-kun , Peng Yan-Wen , Wu Qiong-Li , Liang Feng-Yin , You Hua-Jing , Feng Yi-Wei , Li Ge , Li Xue-jiao , Liu Shu-Hua , Li Yong-Chao , Zhang Yu , Pei Zhong 
Published: June 2020

Abstract
Background
The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD.
Methods
In this study, live Pg were orally administrated to animals, three times a week for one month. Pg-derived lipopolysaccharide (LPS) was used to stimulate peripheral blood mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression.
Results
Dopaminergic neurons in the substantia nigra were reduced and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) were detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice.
Conclusions
These findings suggest that LRRK2 causes gut leakage and further mediates peripheral IL-17A response in Pg-treated animals. We, thus, put forward the hypothesis that IL-17A in the serum may result in activation of the IL-17A-IL-17RA axis that aggravates dysfunction of dopaminergic neurons and provokes microglial activation in LRRK2 R1441G mice.
Considerations for the Use of Serum IgG4, Total Bilirubin (TBIL)and the IgG4/TBIL Ratioindifferential Diagnosis Between IgG4-related Sclerosing Cholangitis and Cholangiocarcinoma
Authors: Xiao Jianchun , Zhou Wenzhe , Hong Tao , Li Binglu , Liu Wei , He Xiaodong , Zheng Chaoji 
Published: June 2020

Abstract
Background:Obstructive jaundice is the most frequent even theonly manifestation of both IgG4-related sclerosing cholangitis (IgG4-SC) and Cholangiocarcinoma(CCA). It was difficult to distinguish this two diseases, though the treatment strategies were quite different. Serum IgG4elevation was most frequently seen in IgG4-SC patients, yet the significantly elevated serum IgG4 in several CCA patients should not be neglected. Likewise, the serum level of IgG4 could be interfered by the serumlevel of TBIL.None of the previous research effort examined the differentiation potential of serumIgG4, CA19-9, TBIL and theIgG4/TBIL ratio for IgG4-SC and CCA. Methods: Atotalof202cases(131 cases of CCA and 71 cases of IgG4-SC) with pathology results were retrospectively registered. The data of serum IgG4,TBIL and the IgG4/TBIL ratio was captured. ROC-curve analysis was then applied to calculatedthe optimal cutoff values.Results: A significantly higher number of IgG4-SC patients experienced abdominal pain than CCA patients (P = 0.006).Elevationof the serum IgG4observedin IgG4-SCandCCAcasesshowed significant differences(P<0.0001). The optimal value of theIgG4 and the ratio was 1780 (95.3% sensitivity and 94.9% specificity) and 36.10 (96.9% sensitivity and 94.9% specificity)for differential diagnosis of IgG4-SC, respectively.For patients with elevation of serum IgG4 ranging from 650 to 3000 mg/L in 30.1% of all patients and 28.1% IAC patients, the serum levels of IgG4 and the ratio showed stronger differential diagnostic power (AUC=0.873 and AUC=0.968, respectively). The optimal value of the sIgG4 and the ratio was 1685 (with 88.9% sensitivity and 84.2% specificity) and 56.02 (94.4% sensitivity, 94.7% specificity). The combination of serum IgG4 and the IgG4/TBILpresentedhigher specificity(98.5%) andaccuracy(99.2%).Conclusion:The differences were significant in the serumlevel of IgG4, CA19-9 and the ratio. The IgG4/TBIL ratio has strongerdiscriminationefficiencythan the serum level of IgG4 or TBIL alonefor patients with elevation of serum IgG4 ranging from 650 to 3000 mg/L. The combination of the IgG4 and the IgG4/TBIL ratio could further enhance the specificity and accuracy for differentiatingIgG4-SCfrom CCA, especially in patients with serum IgG4 from 650 to 3000 mg/L.
Myocardial Infarction Biomarker Discovery with Integrated Gene Expression, Pathways and Biological Networks analysis
Authors: MUJALLI Abdulrahman , Banaganapalli Babajan , Shaik Noor A. , Elango Ramu , Al-Aama Jumana Y. 
Published: June 2020

Abstract
Background
Myocardial infarction (MI) is the most prevalent coronary atherosclerotic heart disease caused by the complex molecular interactions between multiple genes and environment. Molecular exploration of gene expression changes in MI patients is very crucial not just to understand the molecular basis of disease development but also to identify potential therapeutic targets. Therefore, we aim to identify potential biomarkers for the disease development mechanisms and for prognosis of MI using extensive integrated biological network analysis.
Methodology
Gene expression datasets (GSE66360) generated from 51 healthy controls and 49 endothelial cell samples from patients experiencing acute MI were used to analyze the differentially expressed genes (DEG), protein-protein interactions (PPI), gene network-clusters to annotate the candidate pathways relevant to MI pathogenesis.
Results
Bioinformatic analysis revealed 810 DEGs, between control and MI samples, with 574 up- and 236 down- regulated genes. Their functional annotations with Gene Ontology (GO) has captured several MI targeting biological processes like immune response, inflammation and platelets degranulation. Most significantly DEGs enriched KEGG pathways are related to the following functions: Cytokine-cytokine receptor interaction, TNF and NFkB signaling. By constructing the PPI network using STRING and CytoHubba, seventeen hub and bottleneck genes were found, whose involvement in MI was further confirmed by DisGeNET data. Search in the Open Target Platform reveal unique bottleneck genes as potential target for MI.
Conclusion
Our integrative bioinformatics analysis of large-scale gene expression data has identified several potential genetic biomarkers associated with early stage MI providing a new insight into molecular mechanism underlying the disease.
Significance of the Viral Load of High-risk Hpv in the Diagnosis and Prediction of Cervical Lesions: A Retrospective Study
Authors: Liu Yang , Xu Changjun , Pan Jing , Sun Chunyi , Zhou Honglin 
Published: June 2020

Abstract
Background: The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk (HR)-HPV viral load and different cervical lesion degrees.Methods: This was a retrospective study of the patients who first visited the hospital between January 2015 and June 2018. Patients with positive HR-HPV were screening for cervical cancer. The HR-HPV DNA load was measured by the second generation hybrid capture (HC2) technology. The patients grouped as normal, CIN I, CIN II, CIN III, and cervical cancer. Multivariable logistic regression was performed to explore the association between HR-HPV DNA load and cervical lesions.Results: Finally, 265 patients were grouped as normal (n=125), CIN I (n=51), CIN II (n=23), CIN III (n=46), and cervical cancer (n=20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN I (CIN I: OR=3.959, 95%CI: 1.300-12.059, P=0.015) CIN II (OR=6.211, 95%CI: 1.641-23.513, P=0.007), CIN III (OR=7.002, 95%CI: 2.308-21.244, P=0.001), and cervical cancer (OR=9.439, 95%CI: 2.394-37.22, P=0.001).Conclusion: Cervical lesions are closely related to HR-HPV infection. Higher HR-HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.
“Andrà tutto bene”. The effect of character strengths on psychological distress and self-efficacy during Covid-19 lockdown
Authors: Casali Nicole , Feraco Tommaso , Ghisi Marta , Meneghetti Chiara 
Published: June 2020

Abstract
The Covid-19 pandemic obliged people around the world to stay home and self-isolate, with a number of negative psychological consequences. This study focuses on the protective role of character strengths in sustaining mental health and self-efficacy during lockdown. Data were collected from 944 Italian respondents (mean age = 37.24 years, SD = 14.50) by means of an online survey investigating character strengths, psychological distress and Covid-19-related self-efficacy one month after lockdown began. Using principal component analysis, four strengths factors were extracted, namely transcendence, interpersonal, openness and restraint. Regression models showed that transcendence strengths had a strong inverse association with psychological distress, and a positive association with self-efficacy. Openness showed an unexpected direct effect on psychological distress. These results provide original evidence of the importance of character strengths, and transcendence strengths in particular, in supporting mental health and self-efficacy in a pandemic and are discussed within the field of positive psychology.