bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNF Produced by Inflammatory Blood Mononuclear Cells Directly Contributes to Cartilage Damage in Arthritis
Authors: Yarilina Anna , Melim Terry , Kaymakcalan Zehra 
Published: January 2020

Abstract
Background Anti-TNF therapies are effective at preventing inflammation and structural damage in rheumatoid arthritis (RA). However, the role of TNF in cartilage destruction in RA is not well understood. Therefore, we studied the effects of TNF on cartilage and compared TNF production by different cell types involved in joint pathology.Methods Primary human chondrocytes and cartilage explants were cultured with recombinant TNF. Bovine cartilage was co-cultured with activated human peripheral blood mononuclear cells (PBMCs) or fibroblast-like synoviocytes (FLS). Expression of cytokines and metalloproteinases (MMPs) was assessed by qPCR and MSD, and proteoglycan depletion from cartilage was assessed using histomorphometry and colorimetric detection in tissue culture supernatants. D2E7 was used to block TNF both in vitro and in vivo in a human TNF transgenic (hTNF-Tg) mouse model of arthritis.Results TNF elicited strong pro-inflammatory and catabolic effects on isolated human chondrocytes and cartilage explants leading to upregulation of IL-6 and MMPs, as well as proteoglycan depletion from bovine cartilage explants. In an effort to identify cellular sources of TNF, we challenged chondrocytes, FLS and PBMCs with inflammatory stimuli present in RA joints and found that PBMC that were used to model inflammatory cell infiltration produced significantly higher levels of TNF. Moreover, co-culture with activated PBMCs resulted in proteoglycan depletion from bovine cartilage explants. In sharp contrast with stromal cells, TNF failed to induce high amounts of IL-6 and MMPs in PBMCs, suggesting that different cell populations play distinct roles in the triggering and propagation of joint destruction. TNF blockade protected cartilage from damage both in co-culture systems and in a hTNF-Tg mouse model of arthritis.ConclusionsOur data demonstrate that TNF directly triggers a catabolic program in human chondrocytes leading to cartilage damage and further suggest that neutralization of TNF produced by immune cells infiltrating the inflamed joints, decreases catabolic activity of chondrocytes and fibroblasts, which, in turn, contributes to the cartilage protective effects of anti-TNF biologics in arthritis.
Secular trends in testosterone- findings from a large state-mandate care provider
Authors: Chodick Gabriel , Epstein Shdema , Shalev Varda 
Published: January 2020

Abstract
Background Several studies from the US and Europe have shown a population-level decline in serum testosterone in men from 1970's to early 2000's. However, to the best of our knowledge, no study examining population-level decline in testosterone has been published in more recent years. The study objective was therefore to examine secular trends in testosterone levels among Israeli men in the first and second decades of the 21 st century,Methods All incident total testosterone performed between1/2006 and 3/2019 among 102,334 male members of a large health organization.Results A prominent trend of age-independent decline in the testosterone levels for most age groups. The results were highly significant ( Common.EditSubmissionSteps.Transform.EquationText )Conclusions The results show a highly significant age-independent decline in total testosterone that is unlikely to be explained by increasing rates of obesity.
Parasite load and genotype are associated with clinical outcome of piroplasm infected equines
Authors: Tirosh-Levy Sharon , Stienman Amir , Levy Hadas , Katz Yotam , Shtilman Margarita , Gottlieb Yuval 
Published: January 2020

Abstract
Background: Equine piroplasmosis (EP) is a highly endemic protozoan disease of horses worldwide. While most horses in endemic areas are subclinically infected, the mechanisms leading to clinical outcome are vastly unknown. Moreover, since clinical signs of disease are not specific, and the prevalence in endemic areas is high, it is difficult to determine if EP is the cause of disease. To identify possible mechanisms leading to the clinical outcome in an endemic area, we compared parasite loads and genotypes in clinically and subclinically infected horses.Methods: Blood was collected from horses with clinical signs consistent with EP, and from apparently healthy horses from various locations. Packed cell volume (PCV) and total solids (TS) were measured from each sample. Quantitative and diagnostic PCR were used to quantify and classify EP infection in clinical and subclinical horses.Results: For both parasites, clinical cases were associated with low mean packed cell volume (PCV) and high mean parasite load (P<0.001), enabling to determine a cutoff value between clinically and subclinically infected horses. Theileria equi of subclinical horses classified into three different 18S rRNA genotypes: D (=23), A (n=12) and C (n=5), while all clinical cases classified as genotype A. The sequences of T. equi equi merozoite antigen-1 (ema-1) gene were fairly conserved and all classified as genotype A. The ema-2 sequences were analyzed with all currently published sequences and were mostly classified into one genotype (A) among the three resolved genotypes. Babesia caballi rhoptry associated protein-1 (rap-1) was classified into sub-genotypes A1 (n=14) and A2 (n=5) with no association to clinical outcome. Classification of the 18S rRNA gene (sub-genotypes B1 and B2) was in agreement with the rap-1 classification.Conclusions: The results of this study suggest that quantification of parasite loads of infected horses may be used to distinguish between clinical and subclinical cases. Additionally, we identified T. equi 18S rRNA genotype A to be associated with clinical disease. This finding emphasizes the importance of in-depth genetic characterization of T. equi genotypes to identify possible markers for virulence.
(w)HOL(e)ISTIC gene ontology and pathway analysis of data using open source web tools
Authors: Fleming Damarius S. , Miller Laura 
Published: January 2020

Abstract
Objective Downstream analysis of next generation sequencing (NGS) experiments provides researchers a means of deciphering their results. These downstream analyses elucidate clusters of genes or networks of biological interest under the conditions being studied. One convention for examining gene interactions is to conduct downstream investigations based on gene ontology (GO), pathway, and network analyses of statistically significant genes of interest. Unfortunately, the software available for these types of analyses is expensive, not species specific, and subject to gaps in annotation. These difficulties can cause studies to omit this downstream step, limiting the utility of the data. In order to facilitate pathway and network analyses of candidate gene lists from NGS studies, a workflow was constructed based on the use of open-sourced freely available software and genomic databases termed the “(w)HOL(e)ISTIC GO enrichment” approach.Results Overlap of multiple open-source software was used to annotate, analyze, and visualize biological networks. It is a 3-stage process in which stage 1 (Annotation) is the generation of alias identifiers. Stage 2 (Analysis) is a two-part process generating ontologies and networks with statistical inferences. Stage 2 relies on information from databases such as Reactome, KEGG, and InterPro. Stage 3 (Visualization) allows for figure creation.
Isolation and Identification of Kidney-derived Pathogenic Escherichia coli from Red Panda (Ailurus fulgens)
Authors: Liu Songrui , Li Yunli , Yue Chanjuan , Zhang Dongsheng , Su Xiaoyan , Yan Xia , Yang Kuixing , Chen Xin , Zhuo Guifu , Cai Tong , Liu Jiangfeng , Peng Xi , Hou Rong 
Published: January 2020

Abstract
Background Disease prevention and control is a significant part during the ex-situ conservation of the red panda (Ailurus fulgens) with bacterial infection being one of the important threats to the health of the captive population. So far, there was no systematic and detailed publications about the red panda-related E. coli disease. This study was conducted for the purpose of determining the cause of death, etiology and pathogenesis on a red panda through clinical symptoms, complete blood count, biochemical analysis, pathological diagnosis, antimicrobial susceptibility test, mouse pathogenicity test, and bacterial whole genome sequencing.Results A bacterial strain confirmed as Uropathogenic Escherichia coli (UPEC) was isolated from one captive dead red panda, which is resistant to most of the β-lactam drugs and a small number of aminoglycoside medications. The mouse pathogenicity test results showed the strains isolated postmortem from mice were the same as from the dead red panda, and the pathological findings were similar to the red panda while they were not completely the same. These pathological differences between red panda and mice may be related to the routes of infection and perhaps species differences and tolerance. The whole genome sequencing results showed that the isolated strain contained P pili, type I pili and iron uptake system related factors, which were closely related to its nephrotoxicity. Conclusion The red panda died of bacterial infection which was identified as Uropathogenic Escherichia coli. The pathogenic mechanisms of the strain are closely related to the expression of specific virulence genes.
Bioinformatics of Thymidine metabolism in camels and Trypanosoma evansi: nucleoside deoxyribosyltransferase (NDRT) as a drug target
Authors: Kandeel Mahmoud , Al-Taher Abdulla 
Published: January 2020

Abstract
Background Trypanosoma evansi (T. evansi), the causative agent for surra or camel trypanosomiasis, is characterized by the widest geographic distribution and infects the widest range of hosts among the known trypanosomes. The recent zoonotic importance and increasing reports of drug resistance necessitate the discovery of new drug targets. Drug discovery process entails finding an interesting difference between the host and the parasite. Results In this study, the thymidine metabolic pathways were compared in camel and T. evansi. Metabolic maps, protein sequence comparisons, domain and motifs contents analysis, phylogenetic relations and 3D structure models were used in comparisons. A unique difference in thymidine metabolism was at the level of recycling of thymidine which was performed by thymidine phosphorylase in camel, while this role is T. evansi was associated with nucleoside deoxyribosyltransferase (NDRT), which is a unique enzyme for the trypanosome and was absent in camel. Thymidine in T. evansi seems to be governed by thymine through NDRT. In contrast to camel, in which thymidine can be produced from thymidylate by the action of 5'-nucleotidase. Conclusions NDRT can be regarded as a drug target against T. evansi for its strict presence in the parasite but not in the host.
Antiviral effect of copper chloride on feline calicivirus and Synergy with Ribavirin in vitro
Authors: li dengliang , Cui Zhanding , Li Guohua , Zhang Liangting , Zhang Ying , Zhao Han , Zhang Shuang , Guo Yanbing , Zhao Yanli , Men Fanxing , Zhao Shihui , Shao Jiang , Du Dongju , Huang Hailong , Wang Kai , Hu Guixue , Li Tiansong , Zhao Yongkun 
Published: January 2020

Abstract
Background: Feline calicivirus (FCV) is a common pathogen causing widely prevalent upper respiratory disease for kitten and felines in recent years. Due to the substantial genetic variability of the viral genes, existing vaccines cannot provide complete protection. Therefore, researches on FCV antiviral drugs have received much attention. Results: In this study, we found that copper chloride had dose-dependent antiviral effects against FCV in F81 cells. We also found that the combination of copper chloride and ribavirin had a synergistic effect against FCV in the F81 cells. In contrast, the combination of and horse anti-FCV immunoglobulin F(ab’)2 showed an antagonistic effect, likely because the copper chloride has an effect on the F(ab’)2 immunoglobulin; however, further research is needed to clarify this supposition.Conclusions: In summary, we found that copper chloride had low cytotoxicity and significant antiviral effects against FCV in F81 cells, providing a new drug candidate for the prevention and treatment of FCV infection.
Comparison of general maternal and neonatal conditions and clinical outcomes between embryo transfer and natural conception
Authors: Pan Haiyan , Zhang Xingshan , Rao Jiawei , Lin Bing , He JieYun , Wang Xingjie , Han Fengqiong , Zhang Jinfeng 
Published: January 2020

Abstract
Objective: To examine the differences between pregnant women who underwent embryo transfer (ET) and those who conceived naturally, as well as differences in their respective babies, and to determine the causes for these differences, to provide recommendations for women who are planning to undergo ET.Methods: A retrospective cohort study was performed of women who had received ET and those who had natural conception (NC) who received medical services during pregnancy and had their babies delivered at the Shunde Women and Children's Hospital of Guangdong Medical University, China between January 2016 and December 2018. Each case in an ET group of 321 women was randomly matched with three cases of NC (963 cases) who delivered on the same day. The demographic information, past history, pregnancy and delivery history, and maternal and neonatal outcomes of the two groups were compared using univariate analysis.Results: Age, occupation, duration of hospitalization, number of pregnancies, number of miscarriages, induced abortion, ectopic pregnancy, gestational diabetes mellitus, preeclampsia, gestational anemia, pregnancy risk, mode of fetal delivery, and number of births were significantly different between the two groups (all P<0.05). However, there were no significant differences in the disease, allergy and blood transfusion histories of the pregnant women, or differences in prevalence of gestational hypothyroidism, gestational respiratory infection, premature rupture of membrane, placental abruption, fetal death, stillbirth, amniotic fluid volume and amniotic fluid clarity between the two groups (all P>0.05).The percentages for low birth weight and premature birth were significantly higher in the ET group than in the NC group, while the incidence of nuchal cord was higher in the NC group (all P>0.05). In contrast, infant gender and prevalence of fetal macrosomia, fetal anomaly, neonatal asphyxia, and extremely low birth weight were not significantly different between the two groups (all P>0.05).Conclusions: The clinical outcomes of mothers and the birth status of infants were better in the NC group than in the ET group. Maternal health must be closely monitored and improved in the ET group to reduce the incidence of gestational comorbidity and enhance the quality of fetal life.
ANÁLISE DE LEGISLAÇÕES RELATIVAS À GESTÃO DE CHEIAS URBANAS NO ESTADO DO RIO DE JANEIRO
Authors: Fontes da Luz Anna Carolina , Miranda Pinto Augusto Eduardo , Umbelino dos Santos Luis Felipe , Lugon Junior Jader 
Published: January 2020

A impermeabilização dos solos e o processo de urbanização vem tornando os eventos de cheias urbanas cada vez mais frequentes na maior parte do território brasileiro e do mundo, assim o sistema tradicional de drenagem não é capaz de atender toda a demanda, causando problemas à sociedade. Nesse sentido, o estudo de novos sistemas de drenagem, como as técnicas compensatórias, são fundamentais para complementar os sistemas já existentes. Neste trabalho apresenta-se os resultados da pesquisa dos principais instrumentos legais de gestão internacional e nacional de cheias urbanas, com foco no estado do Rio de Janeiro e englobando a região metropolitana e o interior do estado. O objetivo do trabalho foi de realizar um levantamento das legislações pertinentes à gestão de cheias urbanas de determinadas cidades do estado do Rio de Janeiro, de forma que fosse possível analisar se existe alguma relação entre elas e entre as características regionais das diferentes localidades. Assim, foi possível perceber que já existe uma movimentação no estado do Rio de Janeiro para implementação das técnicas compensatórias, tanto na região metropolitana quanto no interior, motivados pelos severos eventos locais já ocorridos. Porém, é preciso dar atenção às características específicas de cada região afim de se obter resultados realmente significativos e auxiliar na melhoria da qualidade de vida da população
Structure-based Virtual Screening Approach for the Discovery of Potent Inhibitors of Aminoglycoside 6'-N-Acetyltransferase Type Ib [AAC(6')-Ib] against K. pneumoniae Infections
Authors: Uddin Reaz , Siraj Bushra , Rafi Sidra , Azam Syed Sikander , Wadood Abdul 
Published: January 2020

Background:Aminoglycoside 6'-N-acetyltransferase type Ib (AAC(6')-Ib) from Klebsiella pneumoniae is an established drug target and has conferred insensitivity to aminoglycosides. Aminoglycosides are often inactivated by aminoglycoside modifying enzymes encoded by genes present in the chromosome, plasmids, and other genetic elements. The AAC(6′)- Ib is an enzyme of clinical importance found in a wide variety of gram-negative pathogens. The AAC(6′)-Ib enzyme is of interest not only because of its ubiquity but also because of other characteristics e.g., it presents significant microheterogeneity at the N-termini and the aac(6′)-Ib gene is often present in integrons, transposons, plasmids, genomic islands, and other genetic structures. The majority of the reported potent inhibitors against the target are substrate analogs. Therefore, there is a need to develop or discover new scaffolds other than substrate analogs as AAC(6')-Ib inhibitor.Objective:The objective of this study is to set optimum parameters for the structure-based virtual screening by multiple docking and scoring methods. The multiple scoring of each ligand also incorporates the ‘Induced Fit’ docking effect that helps to build further confidence in the shortlisted compounds. The method eventually is able to predict the potential inhibitors that bind to the active site and can potentially inhibit the activity of the Aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6’)-Ib] from Klebsiella pneumoniae.Methods:Using the available three-dimensional structure of enzyme AAC(6')-Ib inhibitor complex, a structure-based virtual screening was performed with the hope of prioritizing the promising leads. In order to set up the protocol, 30,000 drug-like molecules were selected from the ChemBridge library. Multiple docking programs, i.e. UCSF DOCK6 and AutoDock Vina have been applied in the current study so that a consensus is developed to the predicted binding modes and thus the docking accuracy. The Amber scores of the Dock6 – a secondary scoring function was also used to perform the ‘Induced Fit’ effect and correspondingly re-rank the compounds.Results:The top 30 ranked compounds of the most frequent scored were selected from the histogram. The 2D interactions of those 30 compounds were drawn from the Ligplot+ tool. Six of the compounds were prioritized as potential inhibitors as they are representing the maximum number of interactions from the rest of the compounds and also possess the drug-likeness as predicted by the estimated ADMET properties.Conclusion:This study provided useful insight that the proposed compounds have the potential to bind to the aminoglycoside binding site of AAC(6′)-Ib that may eventually inhibit the Klebsiella pneumoniae. This study has the potential to propose putative new and novel inhibitors against a resistant drug target of Klebsiella pneumoniae.
Simultaneous Determination of Lamotrigine, Topiramate, Oxcarbazepine, and 10,11-dihydro-10-hydroxycarbazepine in Human Blood Plasma by UHPLC-MS/MS
Authors: Zhao Qing , Jin Siyao , Liu Qingyang , Zhao Zhigang , Feng Weixing , Mei Shenghui 
Published: January 2020

Background:
Lamotrigine (LTG), topiramate (TPM), and oxcarbazepine (OXC) are
commonly used antiepileptic drugs. The bioactivity and toxicity of these drugs were related to their
blood concentrations which varied greatly among individuals and required to be monitored for dose
adjustment. However, the commercial method for monitoring of these drugs is not available in China.

Methods:
A UHPLC-MS/MS method for simultaneous determination of LTG, TPM, OXC, and OXC
active metabolite (10,11-dihydro-10-hydroxycarbazepine, MHD) was developed and validated according
to the guidelines and applied in clinical practice.

Results:
he separation was achieved by using methanol and water (both contain 0.1% formic acid)
at 0.4 mL/min under gradient elution within 3 min. For all analytes, the isotope internal standard was
used; the selectivity was good without significant carry over; LTG and TPM were linear between
0.06 to 12 mg/L while OXC and MHD were linear between 0.03 to 6 mg/L, the upper limit could be
10-fold higher because 10-fold dilution with water did not affect the results; the intra-day and interday
bias and imprecision were -13.11% to 5.42% and < 13.32%; the internal standard normalized recovery
and matrix factor were 90.95% to 111.94% and 95.57% to 109.91%; and all analytes were
stable under tested conditions. LTG and OXC-D4 shared two ion pairs m/z 257.1 > 212.0 and 257.1 >
184.0, and m/z 257.1 > 240.0 was suggested for OXC-D4 quantitation. Lamotrigine and lamotrigine-
13C3 shared three ion pairs m/z 259.0 > 214.0, 259.0 > 168.0 and 259.0 > 159.0, and m/z 259.0 >
144.9 was suggested for LTG-13C3 quantitation. CBZ had a slight influence on OXC analysis only at
0.225 mg/L (bias, 20.24%) but did not affect MHD analysis. Optimization of chromatography conditions
was useful to avoid the influence of isobaric mass transitions on analysis. This method has been
successfully applied in 208 patients with epilepsy for dose adjustment.

Conclusions:
An accurate, robust, rapid, and simple method for simultaneous determination of LTG,
TPM, OXC, and MHD by UHPLC-MS/MS was developed, validated, and successfully applied in patients
with epilepsy for dose adjustment. The experiences during method development, validation,
and application might be helpful for other researchers.
A Facile Synthesis of Anatase Ni2+ Doped TiO2 Nanorods with Highly Improved Visible-Light Photocatalytic Performance
Authors: Nagaraj G. , Senthil R.A. , Boddula Rajender , Ravichandaran K. 
Published: January 2020

Objective:
Herein, we reported a simple and effective approach to synthesis of pure and
Ni2+ doped TiO2 nanorods by a photon-induced method (PIM) followed by calcination at 850 ºC in
air atmosphere.

Methods:
Basically, the PIM was used to tuning the properties of as-prepared TiO2 photocatalyst.
These obtained samples were further characterized by X-ray diffraction (XRD), scanning electron
microscopy (SEM), high resolution transmission electron microscopy (HR-TEM) and UV-visible
diffuse reflectance spectroscopy (UV-vis DRS) analysis. XRD results reveals that the both pure TiO2
and Ni doped TiO2 nanorods has anatase phase up to 850°C.

Results:
The HR-TEM analysis indicates that doping Ni is favourable to the formation of rod-like
TiO2 sample. Also, the observed photocatalytic results demonstrates that the Ni doped TiO2 can be
achieved a complete degradation of methylene blue (MB) within 30 min under direct sunlight irradiation
as compared to pure TiO2.

Conclusion:
Therefore, this work revealing the doped Ni has a good potential to modification of
TiO2 with an excellent photocatalytic activity for water treatment applications.