bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeostasis model assessment, serum insulin and their relation to body fat in cats
Authors: Strage Emma M. , Ley Charles J. , Forkman Johannes , Öhlund Malin , Stadig Sarah , Bergh Anna , Ley Cecilia 
Published: January 2021

AbstractBackgroundObesity is associated with insulin resistance (IR) and considered a risk factor for diabetes mellitus (DM) in cats. It has been proposed that homeostasis model assessment (HOMA-IR), which is the product of fasting serum insulin (mU/L) and glucose (mmol/L) divided by 22.5, can be used to indicate IR. The objectives of this study were threefold: (i) to evaluate associations between body fat, fasting insulin, and HOMA-IR, (ii) to determine population-based reference interval of HOMA-IR in healthy lean cats, and (iii) to evaluate biological variation of HOMA-IR and fasting insulin in cats.Results150 cats were grouped as lean or overweight based on body condition score and in 68 of the cats body fat percentage (BF%) was estimated by computed tomography. Fasting serum insulin and glucose concentrations were analysed. Statistical differences in HOMA-IR and insulin between overweight or lean cats were evaluated using Wilcoxon rank-sum test. Robust method with Box-Cox transformation was used for calculating HOMA-IR reference interval in healthy lean cats. Relations between BF% and HOMA-IR and insulin were evaluated by regression analysis. Restricted maximum likelihood ratio was used to calculate indices of biological variation of HOMA-IR and insulin in seven cats.There were significant differences between groups with overweight cats (n = 77) having higher HOMA-IR (p < 0.0001) and insulin (p = 0.0002) than lean cats (n = 73). Reference interval for HOMA-IR in lean cats was 0.1–3.0. HOMA-IR and fasting insulin concentrations showed similar significant positive association with BF% (p = 0.0010 andp = 0.0017, respectively). Within-animal coefficient of variation of HOMA-IR and insulin was 51% and 49%, respectively.ConclusionsHOMA-IR and fasting insulin higher in overweight than lean cats and correlate to BF%. The established population-based reference interval for HOMA-IR as well as the indices of biological variation for HOMA-IR and fasting insulin may be used when interpreting HOMA-IR and fasting insulin in cats. Further studies are needed to evaluate if HOMA-IR or fasting insulin is useful for identifying cats at risk of developing DM.
Molecular characterisation of extended-spectrum ß-lactamase producing Escherichia coli in wild birds and cattle, Ibadan, Nigeria
Authors: Fashae Kayode , Engelmann Ines , Monecke Stefan , Braun Sascha D. , Ehricht Ralf 
Published: January 2021

AbstractBackgroundAntimicrobial resistance (AMR) is an increasing global health concern reducing options for therapy of infections and also for perioperative prophylaxis. ManyEnterobacteriaceae cannot be treated anymore with third generation cephalosporins (3GC) due to the production of certain 3GC hydrolysing enzymes (extended spectrum beta-lactamases, ESBLs). The role of animals as carriers and vectors of multi-resistant bacteria in different geographical regions is poorly understood. Therefore, we investigated the occurrence and molecular characteristics of ESBL-producingEscherichia coli(E. coli) in wild birds and slaughtered cattle in Ibadan, Nigeria.Cattle faecal samples (n= 250) and wild bird pooled faecal samples (cattle egrets,Bubulcus ibis,n= 28; white-faced whistling duck,Dendrocygna viduata, n= 24) were collected and cultured on cefotaxime-eosin methylene blue agar. Antimicrobial susceptibility was determined by agar diffusion assays and all 3GC resistant isolates were genotypically characterised for AMR genes, virulence associated genes (VAGs) and serotypes using DNA microarray-based assays.ResultsAll 3GC resistant isolates wereE. coli: cattle (n= 53), egrets (n= 87) and whistling duck (n= 4); cultured from 32/250 (12.8%), 26/28 (92.9%), 2/24(8.3%), cattle, egrets and whistling duck faecal samples, respectively.blaCTX-M gene family was prevalent;blaCTX-M15 (83.3%) predominated overblaCTX-M9 (11.8%). All were susceptible to carbapenems. The majority of isolates were resistant to at least one of the other tested antimicrobials; multidrug resistance was highest in the isolates recovered from egrets.The isolates harboured diverse repositories of other AMR genes (includingstrBand sul2), integrons (predominantly class 1) and VAGs. The isolates recovered from egrets harboured more AMR genes; eight were unique to these isolates includingtetG,gepA, andfloR. The prevalent VAGs includedhemLandiss; while 14 (includingsepA) were unique to certain animal isolates. E. coliserotypes O9:H9, O9:H30 and O9:H4 predominated. An identical phenotypic microarray profile was detected in three isolates from egrets and cattle, indicative of a clonal relationship amongst these isolates.ConclusionWild birds and cattle harbour diverse ESBL-producingE. colipopulations with potential of inter-species dissemination and virulence. Recommended guidelines to balance public health and habitat conservation should be implemented with continuous surveillance.
Recombinant adenovirus expressing vesicular stomatitis virus G proteins induce both humoral and cell-mediated immune responses in mice and goats
Authors: Xue Xiaojuan , Yu Zhaorong , Jin Hongyan , Liang Lin , Li Jiayang , Li Xiaolu , Wang Yong , Cui Shangjin , Li Gang 
Published: January 2021

Abstract
Background
Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines.

Results
Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups.

Conclusions
The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.
Aquaporin-4 protein expression in normal canine brains
Authors: Álvarez Patricia , Blasco Ester , Pumarola Martí , Wessmann Annette 
Published: January 2021

Abstract
Background
Aquaporin-4 (AQP4) is in growing recognition as potential marker for cancer progression, differentiation and therapeutic intervention. No information is available about AQP4 expression in the normal canine brain. The aim of this histopathological study is to confirm the presence of AQP4 by immunohistochemistry technique in a group of non-pathological canine brains and to describe its expression and distribution across the brain.

Results
Twelve non-pathological canine brains of various ages (ranging from 21 days to 17 years) and breeds were included in the study. Immunohistochemical expression of AQP4 was analyzed using formalin-fixed paraffin-embedded brain tissue sections. The findings were correlated between AQP4 expressing cells and astrocytes using glial fibrillary acidic protein (GFAP). AQP4 expression was more marked in the astrocyte foot processes of subpial, perivascular and periventricular surfaces in all specimens. The majority of the canine brain sections (9/12) presented with an AQP4 predilection for white matter tracts. Interestingly, the two youngest dogs (21 days and 3 months old) were characterized by diffuse AQP4 labelling in both grey and white matter tracts. This result may suggest that brain development and ageing may play a role in the AQP4 distribution throughout the canine brain.

Conclusions
This is the first study to describe immunohistochemical distribution of AQP4 in normal canine brains. The AQP4 expression and distribution in non-pathological canine brains was comparable to other species. Larger studies are needed to substantiate the influence of breed and ageing on AQP4 expression in the normal canine brain.
Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study
Authors: Lam Rachel , Kwon Sophia , Riggs Jessica , Sunseri Maria , Crowley George , Schwartz Theresa , Zeig-Owens Rachel , Colbeth Hilary , Halpren Allison , Liu Mengling , Prezant David J. , Nolan Anna 
Published: January 2021

Abstract
Background
Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD.

Methods
WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV1 < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15–19), moderate-(20–29), and high-(30–39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description.

Results
N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD.

Conclusions
REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.
Surfactant therapy for COVID-19 related ARDS: a retrospective case–control pilot study
Authors: Piva Simone , DiBlasi Robert M. , Slee April E. , Jobe Alan H. , Roccaro Aldo M. , Filippini Matteo , Latronico Nicola , Bertoni Michele , Marshall John C. , Portman Michael A. 
Published: January 2021

Abstract
Background
COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established.

Methods
We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality.

Results
Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive.

Conclusions
Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.
Hypoxia-induced Tie1 drives stemness and cisplatin resistance in non-small cell lung carcinoma cells
Authors: Li Chaojie , Yang Nannan , Chen Zhijin , Xia Ning , Shan Qungang , Wang Ziyin , Lu Jian , Shang Mingyi , Wang Zhongmin 
Published: January 2021

Abstract
Background
Drug resistance and metastasis involving hypoxic tumor environments and persistent stem cell populations are detrimental to the survival of patients with non-small cell lung carcinoma (NSCLC). Tie1 is upregulated in hypoxia and is believed to counteract the effectiveness of platinum agents by promoting the stemness properties in cells. We have investigated the association of Tie1 with HIF-1α and cisplatin resistance in NSCLC cell lines.

Methods
The expression of Tie1 in a pulmonary microvascular endothelial cell line (HPMEC) and NSCLC cell lines was detected using qRT-PCR and western blotting. The effect of Tie1 on cell stemness and migration was examined by sphere-forming and transwell assays in NSCLC cells with Tie1 silenced. The regulation of Tie1 by HIF-1α was evaluated by a dual-luciferase reporter assay and chromatin immunoprecipitation.

Results
We found that hypoxia could induce stemness and cisplatin resistance in vitro. Tie1 was expressed at low levels in NSCLC cells when compared with human pulmonary microvascular endothelial cells, however, its expression was increased by hypoxia. Additionally, Tie1 knockdown could reduce stemness properties and increase sensitivity to cisplatin in vitro and in a xenograft mouse model. The promoter of Tie1 contains two predicted hypoxia-response elements (HREs). We mutated both HRE sites and conducted chromatin immune-precipitation and promoter luciferase reporter assays and were able to conclude that the induction of Tie1 by hypoxia was HIF-1α-dependent.

Conclusions
Our findings indicated that Tie1 is upregulated in a hypoxic environment by HIF-1α and contributes to tumorigenesis and cisplatin resistance through the promotion of stemness in NSCLC cells.
The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities
Authors: Nombela Paz , Miguel-López Borja , Blanco Sandra 
Published: January 2021

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.
The inflammatory kinase IKKα phosphorylates and stabilizes c-Myc and enhances its activity
Authors: Moser Bernhard , Hochreiter Bernhard , Basílio José , Gleitsmann Viola , Panhuber Anja , Pardo-Garcia Alan , Hoesel Bastian , Salzmann Manuel , Resch Ulrike , Noreen Mamoona , Schmid Johannes A. 
Published: January 2021

AbstractBackgroundThe IκB kinase (IKK) complex, comprising the two enzymes IKKα and IKKβ, is the main activator of the inflammatory transcription factor NF-κB, which is constitutively active in many cancers. While several connections between NF-κB signaling and the oncogene c-Myc have been shown, functional links between the signaling molecules are still poorly studied.MethodsMolecular interactions were shown by co-immunoprecipitation and FRET microscopy. Phosphorylation of c-Myc was shown by kinases assays and its activity by improved reporter gene systems. CRISPR/Cas9-mediated gene knockout and chemical inhibition were used to block IKK activity. The turnover of c-Myc variants was determined by degradation in presence of cycloheximide and by optical pulse-chase experiments.. Immunofluorescence of mouse prostate tissue and bioinformatics of human datasets were applied to correlate IKKα- and c-Myc levels. Cell proliferation was assessed by EdU incorporation and apoptosis by flow cytometry.ResultsWe show that IKKα and IKKβ bind to c-Myc and phosphorylate it at serines 67/71 within a sequence that is highly conserved. Knockout of IKKα decreased c-Myc-activity and increased its T58-phosphorylation, the target site for GSK3β, triggering polyubiquitination and degradation. c-Myc-mutants mimicking IKK-mediated S67/S71-phosphorylation exhibited slower turnover, higher cell proliferation and lower apoptosis, while the opposite was observed for non-phosphorylatable A67/A71-mutants. A significant positive correlation of c-Myc and IKKα levels was noticed in the prostate epithelium of mice and in a variety of human cancers.ConclusionsOur data imply that IKKα phosphorylates c-Myc on serines-67/71, thereby stabilizing it, leading to increased transcriptional activity, higher proliferation and decreased apoptosis.
The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke
Authors: Lei Tian-Yu , Ye Ying-Ze , Zhu Xi-Qun , Smerin Daniel , Gu Li-Juan , Xiong Xiao-Xing , Zhang Hong-Fei , Jian Zhi-Hong 
Published: January 2021

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.
Aging and CMV discordance are associated with increased immune diversity between monozygotic twins
Authors: Yan Zheng , Maecker Holden T. , Brodin Petter , Nygaard Unni C. , Lyu Shu Chen , Davis Mark M. , Nadeau Kari C. , Andorf Sandra 
Published: January 2021

AbstractBackgroundBroadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development.ResultsTo address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12–31 years) and middle-aged (42–59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system.ConclusionsOur study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.