bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Leishmania infantum infection in equine populations in a canine visceral leishmaniosis transmission area
Authors: Escobar Taiane Acunha , Dowich Gabriela , dos Santos Thália Pacheco , Zuravski Luísa , Duarte Claudia Acosta , Lübeck Irina , Manfredini Vanusa 
Published: October 2019

Abstract

Background
Leishmaniosis, zoonosis that produces significant public health impacts, is caused by Leishmania infantum. Canines are the main domestic reservoir and, besides humans, other species of mammals could be infected when living in endemic areas. In this study, we detected equine Leishmania infantum infections in a canine visceral leishmaniosis transmission area and evaluated the clinical, haematological, biochemical and oxidative stress disorders. This study was conducted in Uruguaiana, Rio Grande do Sul, south of Brazil. Peripheral blood samples were collected from 124 animals (98 horses and 26 dogs) of both genders and several breeds after they underwent general and dermatologic examinations.

Results
Twenty five Leishmania infantum infected animals (20.16%), 14 horses and 11 dogs were detected by PCR (Polymerase Chain Reaction) amplification of kinetoplast DNA regions with 96% homology to Leishmania infantum (GenBank Accession No. L 19877.1). The clinical and haematological alterations of infected equines were skin lesions, nodules, lymphadenopathy, decreased levels in red blood cells and haematocrit (p < 0.05) and increase in urea serum concentration (p < 0.05), while CVL presented a decrease in red blood cells counts (p < 0.05), increase in lymphocytes (p < 0.05), and decrease in neutrophil-lymphocyte ratio (p < 0.05). Oxidative stress markers of plasma protein carbonyl and plasma lipid peroxidation were not statistically significant (p > 0.05) in both species.

Conclusions
To our knowledge, this has been the first leishmaniosis equine survey performed in south of Brazil, caused by Leishmania infantum that were able to initially identify haematological and biochemical changes in the species, even in asymptomatic animals. We present evidence supporting those findings of haematological and biochemical changes could be related to infection. Surprisingly, the clinical manifestations of equine infection were similar to those found in canine visceral leishmaniosis. The equine population could be play an important role in the cycle of leishmaniosis in south Brazil and consequently indicates a great risk of public health. This evaluation of infected animals is important to establish the clinical and laboratory parameters involved in the disease progression.
Detection of ALV p27 in cloacal swabs and virus isolation medium by sELISA
Authors: Zhou Xiaoyu , Wang Lin , Shen Anning , Shen Xi , Xu Moru , Qian Kun , Shao Hongxia , Yao Yongxiu , Nair Venugopal , Ye Jianqiang , Qin Aijian 
Published: October 2019

Abstract

Background
Avian leukosis (AL), which is caused by avian leukosis virus (ALV), has led to substantial economic losses in the poultry industry. The kit used to detect all ALV-positive chickens in breeder flocks is very important for efficiently controlling AL. However, a new emerging ALV subtype is currently a severe challenge in the poultry industry.

Results
In this paper, we compared different enzyme-linked immunosorbent assay (ELISA) kits for detecting p27 of ALV in the same batch of meconium samples. Different positive samples were further analyzed by PCR or virus isolation. The results showed that 36 positive samples among the 1812 chicken meconium samples could be detected by a sandwich ELISA (sELISA) kit, but only 17 positive samples could be identified by a commercial kit. To verify this result, cloacal swabs and viruses isolated from the positive chickens (2 days old) were used to detect the presence of p27. The results showed that the positive rate of p27 was 100% for the swabs and 40% for virus isolation. Surprisingly, PCR and sequence analysis revealed that the env gene of ALV in these positive samples belonged to the novel subgroup K (ALV-K).

Conclusion
These data not only demonstrate the relatively high sensitivity of the sELISA kit but also highlight the challenge of controlling ALV-K.
Epigenetic landscapes suggest that genetic risk for intracranial aneurysm operates on the endothelium
Authors: Poppenberg Kerry E. , Jiang Kaiyu , Tso Michael K. , Snyder Kenneth V. , Siddiqui Adnan H. , Kolega John , Jarvis James N. , Meng Hui , Tutino Vincent M. 
Published: October 2019

AbstractBackgroundGenetics play an important role in intracranial aneurysm (IA) pathophysiology. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are linked to IA but how they affect disease pathobiology remains poorly understood. We used Encyclopedia of DNA Elements (ENCODE) data to investigate the epigenetic landscapes surrounding genetic risk loci to determine if IA-associated SNPs affect functional elements that regulate gene expression and if those SNPs are most likely to impact a specific type of cells.MethodsWe mapped 16 highly significant IA-associated SNPs to linkage disequilibrium (LD) blocks within the human genome. Within these regions, we examined the presence of H3K4me1 and H3K27ac histone marks and CCCTC-binding factor (CTCF) and transcription-factor binding sites using chromatin immunoprecipitation-sequencing (ChIP-Seq) data. This analysis was conducted in several cell types relevant to endothelial (human umbilical vein endothelial cells [HUVECs]) and inflammatory (monocytes, neutrophils, and peripheral blood mononuclear cells [PBMCs]) biology. Gene ontology analysis was performed on genes within extended IA-risk regions to understand which biological processes could be affected by IA-risk SNPs. We also evaluated recently published data that showed differential methylation and differential ribonucleic acid (RNA) expression in IA to investigate the correlation between differentially regulated elements and the IA-risk LD blocks.ResultsThe IA-associated LD blocks were statistically significantly enriched for H3K4me1 and/or H3K27ac marks (markers of enhancer function) in endothelial cells but not in immune cells. The IA-associated LD blocks also contained more binding sites for CTCF in endothelial cells than monocytes, although not statistically significant. Differentially methylated regions of DNA identified in IA tissue were also present in several IA-risk LD blocks, suggesting SNPs could affect this epigenetic machinery. Gene ontology analysis supports that genes affected by IA-risk SNPs are associated with extracellular matrix reorganization and endopeptidase activity.ConclusionThese findings suggest that known genetic alterations linked to IA risk act on endothelial cell function. These alterations do not correlate with IA-associated gene expression signatures of circulating blood cells, which suggests that such signatures are a secondary response reflecting the presence of IA rather than indicating risk for IA.
A comparison of machine learning classifiers for dementia with Lewy bodies using miRNA expression data
Authors: Shigemizu Daichi , Akiyama Shintaro , Asanomi Yuya , Boroevich Keith A. , Sharma Alok , Tsunoda Tatsuhiko , Sakurai Takashi , Ozaki Kouichi , Ochiya Takahiro , Niida Shumpei 
Published: October 2019

AbstractBackgroundDementia with Lewy bodies (DLB) is the second most common subtype of neurodegenerative dementia in humans following Alzheimer’s disease (AD). Present clinical diagnosis of DLB has high specificity and low sensitivity and finding potential biomarkers of prodromal DLB is still challenging. MicroRNAs (miRNAs) have recently received a lot of attention as a source of novel biomarkers.MethodsIn this study, using serum miRNA expression of 478 Japanese individuals, we investigated potential miRNA biomarkers and constructed an optimal risk prediction model based on several machine learning methods: penalized regression, random forest, support vector machine, and gradient boosting decision tree.ResultsThe final risk prediction model, constructed via a gradient boosting decision tree using 180 miRNAs and two clinical features, achieved an accuracy of 0.829 on an independent test set. We further predicted candidate target genes from the miRNAs. Gene set enrichment analysis of the miRNA target genes revealed 6 functional genes included in the DHA signaling pathway associated with DLB pathology. Two of them were further supported by gene-based association studies using a large number of single nucleotide polymorphism markers (BCL2L1:P = 0.012, PIK3R2:P = 0.021).ConclusionsOur proposed prediction model provides an effective tool for DLB classification. Also, a gene-based association test of rare variants revealed that BCL2L1 and PIK3R2 were statistically significantly associated with DLB.
Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
Authors:   On behalf of the BACE trial investigators, Vermeersch Kristina , Belmans Ann , Bogaerts Kris , Gyselinck Iwein , Cardinaels Nina , Gabrovska Maria , Aumann Joseph , Demedts Ingel K. , Corhay Jean-Louis , Marchand Eric , Slabbynck Hans , Haenebalcke Christel , Vermeersch Stefanie , Verleden Geert M. , Troosters Thierry , Ninane Vincent , Brusselle Guy G. , Janssens Wim 
Published: October 2019

AbstractBackgroundIn the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.Objectives(1) To investigate the intervention’s effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.MethodsEnrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time.ResultsAzithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97,p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81,p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80;p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60,p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64,p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses.ConclusionsThis post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy.Trial registrationClinicalTrials.gov number.NCT02135354.
Isolation and characterization of extracellular vesicles from Broncho-alveolar lavage fluid: a review and comparison of different methods
Authors: Carnino Jonathan M. , Lee Heedoo , Jin Yang 
Published: October 2019

Abstract
Extracellular vesicles (EVs) are cell-derived membranous vesicles secreted by cells into the extracellular space, which play a role in cell to cell communication. EVs are categorized into 3 groups depending on their size, surface marker, and method of release from the host cell. Recently, EVs have become of interest in the study of multiple disease etiologies and are believed to be potential biomarkers for many diseases. Multiple different methods have been developed to isolate EVs from different samples such as cell culture medium, serum, blood, and urine. Once isolated, EVs can be characterized by technology such as nanotracking analysis, dynamic light scattering, and nanoscale flow cytometry. In this review, we summarize the current methods of EV isolation, provide details into the three methods of EV characterization, and provide insight into which isolation approaches are most suitable for EV isolation from bronchoalveolar lavage fluid (BALF).
Exploring the key communicator role of exosomes in cancer microenvironment through proteomics
Authors: Kim HuiSu , Kim Dong Wook , Cho Je-Yoel 
Published: October 2019

ABSTRACT
There have been many attempts to fully understand the mechanism of cancer behavior. Yet, how cancers develop and metastasize still remain elusive. Emerging concepts of cancer biology in recent years have focused on the communication of cancer with its microenvironment, since cancer cannot grow and live alone. Cancer needs to communicate with other cells for survival, and thus they secrete various messengers, including exosomes that contain many proteins, miRNAs, mRNAs, etc., for construction of the tumor microenvironment. Moreover, these intercellular communications between cancer and its microenvironment, including stromal cells or distant cells, can promote tumor growth, metastasis, and escape from immune surveillance. In this review, we summarized the role of proteins in the exosome as communicators between cancer and its microenvironment. Consequently, we present cancer specific exosome proteins and their unique roles in the interaction between cancer and its microenvironment. Clinically, these exosomes might provide useful biomarkers for cancer diagnosis and therapeutic tools for cancer treatment.
Complementary biobank of rodent tissue samples to study the effect of World Trade Center exposure on cancer development
Authors: Lieberman-Cribbin Wil , Tuminello Stephanie , Gillezeau Christina , van Gerwen Maaike , Brody Rachel , Mulholland David J. , Horton Lori , Sisco Maureen , Prophete Colette , Zelikoff Judith , Lee Hyun-Wook , Park Sung-Hyun , Chen Lung-Chi , Cohen Mitchell D. , Taioli Emanuela 
Published: October 2019

Abstract
World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort. Here we describe the implementation of a tissue bank system for the rodents experimentally exposed to WTC dust. NYU samples were experimentally exposed to WTC dust via intratracheal inhalation that mimicked conditions in the immediate aftermath of the disaster. Tissue from Mount Sinai was derived from genetically modified mice exposed to WTC dust via nasal instillation. All processed tissues include annotations of the experimental design, WTC dust concentration/dose, exposure route and duration, genetic background of the rodent, and method of tissue isolation/storage. A biobank of tissue from rodents exposed to WTC dust has been compiled representing an important resource for the scientific community. The biobank remains available as a scientific resource for future research through established mechanisms for samples request and utilization. Studies using the WTC tissue bank would benefit from confirming their findings in corresponding tissues from organs of animals experimentally exposed to WTC dust. Studies on rodent tissues will advance the understanding of the biology of the tumors developed by WTC responders and ultimately impact the modalities of treatment, and the probability of success and survival of WTC cancer patients.
Role of non-macrophage cell-derived HMGB1 in oxaliplatin-induced peripheral neuropathy and its prevention by the thrombin/thrombomodulin system in rodents: negative impact of anticoagulants
Authors: Tsubota Maho , Fukuda Ryotaro , Hayashi Yusuke , Miyazaki Takaya , Ueda Shin , Yamashita Rika , Koike Nene , Sekiguchi Fumiko , Wake Hidenori , Wakatsuki Shuji , Ujiie Yuka , Araki Toshiyuki , Nishibori Masahiro , Kawabata Atsufumi 
Published: October 2019

Abstract

Background
Macrophage-derived high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, plays a key role in the development of chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel in rodents. Endothelial thrombomodulin (TM) promotes thrombin-induced degradation of HMGB1, and TMα, a recombinant human soluble TM, abolishes peripheral HMGB1-induced allodynia in mice. We thus examined whether HMGB1, particularly derived from macrophages, contributes to oxaliplatin-induced neuropathy in mice and analyzed the anti-neuropathic activity of the TM/thrombin system.

Methods
CIPN models were created by the administration of oxaliplatin in mice and rats, and the nociceptive threshold was assessed by von Frey test or paw pressure test. Macrophage-like RAW264.7 cells were stimulated with oxaliplatin in vitro. Proteins were detected and/or quantified by Western blotting, immunostaining, or enzyme-linked immunosorbent assay.

Results
Intraperitoneal administration of an anti-HMGB1-neutralizing antibody (AB) at 1 mg/kg prevented the oxaliplatin-induced allodynia in mice and rats. Antagonists of Toll-like receptor (TLR) 4, receptor for advanced glycation end products (RAGE) and CXCR4 among the HMGB1-targeted pro-nociceptive receptors, also mimicked the anti-neuropathic activity of AB in mice. Macrophage accumulation in the sciatic nerve was observed in mice treated with paclitaxel, but not oxaliplatin, and neither macrophage depletion nor inhibitors of macrophage activation affected oxaliplatin-induced allodynia. Oxaliplatin was 10- to 100-fold less potent than paclitaxel in releasing HMGB1 from macrophage-like RAW264.7 cells. Like AB, TMα at 10 mg/kg prevented the oxaliplatin-induced allodynia in mice as well as rats, an effect abolished by argatroban at 10 mg/kg, a thrombin inhibitor. The anti-neuropathic activity of TMα in oxaliplatin-treated mice was suppressed by oral anticoagulants such as warfarin at 1 mg/kg, dabigatran at 75 mg/kg, and rivaroxaban at 10 mg/kg, but not antiplatelet agents such as aspirin at 50 mg/kg and clopidogrel at 10 mg/kg. Repeated administration of the anticoagulants gradually developed neuropathic allodynia and elevated plasma HMGB1 levels in mice treated with a subeffective dose of oxaliplatin.

Conclusions
Our data thus suggests a causative role of HMGB1 derived from non-macrophage cells in oxaliplatin-induced peripheral neuropathy and a thrombin-dependent anti-neuropathic activity of exogenous TMα and, most probably, endogenous TM.
Evaluating the effectiveness of a combined approach to improve utilization of adolescent sexual reproductive health services in Kenya: a quasi-experimental design study protocol
Authors: Mutea Lilian , Ontiri Susan , Macharia Sheila , Tzobotaro Meital , Ajema Carolyne , Odiara Vincent , Kadiri Francis , Orero Solomon , Kabue Mark , Michielsen Kristien , Gichangi Peter 
Published: October 2019

Abstract

Background
Access to and utilization of adolescent sexual and reproductive health (ASRH) services remains poor. ASRH services in Kenya are primarily offered in health facilities and include counselling, information, and services on family planning, sexually transmitted infections, and HIV and basic life skills. The Ministry of Education also provides age-appropriate sexual and reproductive health information in schools. This paper presents a study protocol that will evaluate the effectiveness of a combined approach toward improving utilization of ASRH services.

Methods
This will be a quasi-experimental study utilizing qualitative and quantitative methods. During the formative phase, data will be collected through focus group discussions, in-depth interviews, and key informant interviews to explore the barriers and facilitators of provision and utilization of ASRH services. A quantitative design will be used to obtain baseline and endline data through household surveys and client exit interviews. Following the formative and baseline household and client exit assessments, an intervention focusing on provision of ASRH service package targeting boys and girls will be implemented for 18 months. The package will include contextualized ASRH services, including counselling and age-appropriate, comprehensive sexual education for behavior change with an aim to increase utilization of ASRH services. An analysis of the primary outcome (utilization of ASRH services) will be undertaken to establish the difference in difference between the control and intervention arm, before the intervention (using the baseline survey data) and after the intervention (using the endline survey data).

Discussion
Adolescents have now been included in the World Health Organization’s Global strategy for women’s, children’s and adolescents’ health (2016–2030), acknowledging the unique health challenges facing young people and their pivotal role as drivers of change in the post-2015 era. This study will generate evidence on whether a combined school, facility, and community approach works toward improving utilization of ASRH services. The information generated from the study will be beneficial for programming as it will identify underlying reasons for low utilization of ASRH services. Results will help to shape ASRH programs and reduce teenage pregnancy within Kenya and other similar low middle-income countries.

Trial registration
The study is registered at http://www.pactr.org/, registration number PACTR201906738029948.
Identifying novel biomarkers of the pediatric influenza infection by weighted co-expression network analysis
Authors: Zarei Ghobadi Mohadeseh , Mozhgani Sayed-Hamidreza , Farzanehpour Mahdieh , Behzadian Farida 
Published: October 2019

AbstractBackgroundDespite the high yearly prevalence of Influenza, the pathogenesis mechanism and involved genes have not been fully known. Finding the patterns and mapping the complex interactions between different genes help us to find the possible biomarkers and treatment targets.MethodsHerein, weighted gene co-expression network analysis (WGCNA) was employed to construct a co-expression network among genes identified by microarray analysis of the pediatric influenza-infected samples.ResultsThree of the 38 modules were found as the most related modules to influenza infection. At a functional level, we found that the genes in these modules regulate the immune responses, protein targeting, and defense to virus. Moreover, the analysis of differentially expressed genes disclosed 719 DEGs between the normal and infected subjects. The comprehensive investigation of genes in the module involved in immune system and viral defense (yellow module) revealed thatSP110,HERC5,SAMD9L,RTP4,C19orf66,HELZ2,EPSTI1, andPHF11which were also identified as DEGs (exceptC19orf66) have the potential to be as the biomarkers and also drug targeting for the treatment of pediatric influenza.ConclusionsThe WGCN analysis revealed co-expressed genes which were involved in the innate immune system and defense to virus. The differentially expressed genes in the identified modules can be considered for designing drug targets. Moreover, modules can help to find pathogenesis routes in the future.