bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting total immunoglobulins in diverse animal species with a novel split enzymatic assay
Authors: Drikic Marija , Olsen Steven , De Buck Jeroen 
Published: October 2019

AbstractBackgroundTotal immunolobulin G concentration is a useful, albeit underutilized, diagnostic parameter for health assessments of non-domestic animal species, due to a lack of functional diagnostic tools. Traditional assays, including enzyme-linked immunosorbent assay or radial immunodiffusion, require development of specific reagents (e.g., polyclonal antisera and appropriate protocols) for each animal species, precluding wide and easy adoption in wildlife welfare. As an alternative, bacterial virulence factors able to bind IgGs in antigen-independent manner can be used. To further simplify the diagnostic procedure and increase the number of species recognized by an assay, in this study a recently developed Split Trehalase immunoglobulin assay (STIGA) with bIBPs as a sensing elements was used to detect antibodies in 29 species from 9 orders. Three bacterial immunoglobulin binding proteins (protein G, protein A and protein L) were incorporated into STIGA reagents to increase the number of species recognized.ResultsIgG concentrations were detected through glucose production and produced signals were categorized in 4 categories, from not active to strong signal. Activation was detected in almost all tested animal species, apart from birds. Incorporation of Protein G, Protein A and Protein L allowed detection of IgGs in 62, 15.5 and 6.9% of species with a strong signal, respectively. Assays combining 2 bacterial immunoglobulin binding proteins as sensing element generally gave poorer performance than assays with the same bacterial immunoglobulin binding proteins fused to both trehalase fragments.ConclusionsSTIGA assays have potential to be further developed into an easily adoptable diagnostic test for total amount of IgGs in almost any serum sample, independent of species.
Active roles of dysfunctional vascular endothelium in fibrosis and cancer
Authors: Hsu Tien , Nguyen-Tran Hieu-Huy , Trojanowska Maria 
Published: October 2019

AbstractChronic inflammation is the underlying pathological condition that results in fibrotic diseases. More recently, many forms of cancer have also been linked to chronic tissue inflammation. While stromal immune cells and myofibroblasts have been recognized as major contributors of cytokines and growth factors that foster the formation of fibrotic tissue, the endothelium has traditionally been regarded as a passive player in the pathogenic process, or even as a barrier since it provides a physical divide between the circulating immune cells and the inflamed tissues. Recent findings, however, have indicated that endothelial cells in fact play a crucial role in the inflammatory response. Endothelial cells can be activated by cytokine signaling and express inflammatory markers, which can sustain or exacerbate the inflammatory process. For example, the activated endothelium can recruit and activate leukocytes, thus perpetuating tissue inflammation, while sustained stimulation of endothelial cells may lead to endothelial-to-mesenchymal transition that contributes to fibrosis. Since chronic inflammation has now been recognized as a significant contributing factor to tumorigenesis, it has also emerged that activation of endothelium also occurs in the tumor microenvironment. This review summarizes recent findings characterizing the molecular and cellular changes in the vascular endothelium that contribute to tissue fibrosis, and potentially to cancer formation.
Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
Authors: Chen Chi , Chen Yi , Weng Pan , Xia Fangzhen , Li Qin , Zhai Hualing , Wang Ningjian , Lu Yingli 
Published: October 2019

Abstract

Background
Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology.

Methods
Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria.

Results
Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels.

Conclusions
We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.
Solitary metastasis of myxoid liposarcoma from the thigh to intraperitoneum: a case report
Authors: Kim Dong-Wook , Jee Ye Seob 
Published: October 2019

Abstract

Background
The purpose of case report was to present a rare case of a solitary metastasis of myxoid liposarcoma and discuss the clinical and pathological information for patients treated for metastatic myxoid liposarcoma.

Case presentation
We report our experience with a case of solitary metastasis of myxoid liposarcoma from the thigh to intraperitoneum. The patient was a 60-year-old man who was referred for abdominal discomfort and fatigue. Enhanced computed tomography showed a 25-cm intra-abdominal tumor. He had undergone a wide local excision for a right thigh myxoid liposarcoma 6 years earlier. At laparotomy, a huge multi-lobular cystic mass was identified at the small bowel mesentery. Wide local excision was performed, and the mass was diagnosed as metastatic myxoid liposarcoma. He was discharged without postoperative complications.

Conclusions
We experienced a single intraperitoneal metastasis in a patient with myxoid liposarcoma after radical surgery of the primary site.
Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma
Authors: Ito Masaoki , Codony-Servat Carles , Codony-Servat Jordi , Lligé David , Chaib Imane , Sun Xiaoyan , Miao Jing , Sun Rongwei , Cai Xueting , Verlicchi Alberto , Okada Morihito , Molina-Vila Miguel Angel , Karachaliou Niki , Cao Peng , Rosell Rafael 
Published: October 2019

Abstract

Introduction
p21-activated kinase 1 (PAK1) stimulates growth and metastasis in non-small cell lung cancer (NSCLC). Protein kinase C iota (PKCι) is an enzyme highly expressed in NSCLC, regulating PAK1 signaling. In the present study we explored whether the PKCι-PAK1 signaling pathway approach can be an efficient target in different types of NSCLC cell and mouse models.

Methods
The effect of IPA-3 (PAK1 inhibitor) plus auranofin (PKCι inhibitor) combination was evaluated by cell viability assay, colony formation and western blotting assay, using three types of NSCLC cell lines: EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma with PAK1 amplification. In addition, for clinical availability, screening for new PAK1 inhibitors was carried out and the compound OTSSP167 was evaluated in combination with auranofin in cell and mice models.

Results
The combination of IPA-3 or OTSSP167 plus auranofin showed high synergism for inhibiting cell viability and colony formation in three cell lines. Mechanistic characterization revealed that this drug combination abrogated expression and activation of membrane receptors and downstream signaling proteins crucial in lung cancer: EGFR, MET, PAK1, PKCι, ERK1/2, AKT, YAP1 and mTOR. A nude mouse xenograft assay demonstrated that this drug combination strongly suppressed tumor volume compared with single drug treatment.

Conclusions
Combination of IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma cell lines and decreased tumor volume in mice models. It is of interest to further test the targeting of PKCι-PAK1 signaling pathways in EGFR mutant, KRAS mutant and squamous NSCLC patients.
Prevalence and correlates of adherence to movement guidelines among urban and rural children in Mozambique: a cross-sectional study
Authors: Manyanga Taru , Barnes Joel D. , Chaput Jean-Philippe , Katzmarzyk Peter T. , Prista Antonio , Tremblay Mark S. 
Published: October 2019

Abstract

Background
Insufficient physical activity, short sleep duration, and excessive recreational screen time are increasing globally. Currently, there are little to no data describing prevalences and correlates of movement behaviours among children in low-middle-income countries. The few available reports do not include both urban and rural respondents, despite the large proportion of rural populations in low-middle-income countries. We compared the prevalence of meeting 24-h movement guidelines and examined correlates of meeting the guidelines in a sample of urban and rural Mozambican schoolchildren.

Methods
This is cross-sectional study of 9–11 year-old children (n = 683) recruited from 10 urban and 7 rural schools in Mozambique. Moderate- to vigorous-intensity physical activity (MVPA) and sleep duration were measured by waist-worn Actigraph GT3X+ accelerometers. Accelerometers were worn 24 h/day for up to 8 days. Recreational screen time was self-reported. Potential correlates of meeting 24-h movement guidelines were directly measured or obtained from validated items of context-adapted questionnaires. Multilevel multivariable logit models were used to determine the correlates of movement behaviours. Meeting 24-h movement guidelines was defined as ≥60 min/day of MVPA, ≤2 h/day of recreational screen time, and between 9 and 11 h/night of sleep.

Results
More rural (17.7%) than urban (3.6%) children met all three 24-h movement guidelines. Mean MVPA was lower (82.9 ± 29.5 min/day) among urban than rural children (96.7 ± 31.8 min/day). Rural children had longer sleep duration (8.9 ± 0.7 h/night) and shorter recreational screen time (2.7 ± 1.9 h/day) than their urban counterparts (8.7 ± 0.9 h/night and 5.0 ± 2.3 h/day respectively). Parental education (OR: 0.37; CI: 0.16–0.87), school location (OR: 0.21; CI: 0.09–0.52), and outdoor time (OR: 0.67; CI: 0.53–0.85) were significant correlates of meeting all three 24-h movement guidelines.

Conclusions
Prevalence and correlates of meeting movement guidelines differed between urban and rural schoolchildren in Mozambique. On average, both groups had higher daily MVPA minutes, shorter sleep duration, and higher recreational screen time than the 24-h movement guidelines recommend. These findings (e.g., higher than recommended mean daily MVPA minutes) differ from those from high-income countries and highlight the need to sample from both urban and rural areas.
Effects of VEGF blockade on the dynamics of the inflammatory landscape in glioblastoma-bearing mice
Authors: Soubéran Aurélie , Brustlein Sophie , Gouarné Caroline , Chasson Lionel , Tchoghandjian Aurélie , Malissen Marie , Rougon Geneviève 
Published: October 2019

Abstract

Background
Targeting angiogenesis has been and continues to be an attractive therapeutic modality in glioblastoma (GBM) patients. However, GBM rapidly becomes refractory to anti-VEGF therapies. Myeloid cell infiltration is an important determinant of tumor progression. Given that VEGF is a modulator of the innate immune response we sought to analyze the dynamics of this response in a mouse model of GBM undergoing anti-VEGF therapy.

Methods
We grafted GL261-DsRed cells in transgenic Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We combined recurrent spectral two-photon imaging with multiparametric cytometry, immunostaining, and brain clearing to characterize at two critical stages of tumor development (day 21 and day 28 after tumor grafting) the nature and spatial distribution of the innate response in control and bevacizumab-treated mice.

Results
We report that at an early stage (21 day), VEGF blockade has a detectable effect on the number of microglial cells but only a mild effect on the number of infiltrating myeloid cells. At a later stage (day 28), the treatment resulted in a specific adjustment of dendritic cell subsets. In treated mice, the number of monocytes and their monocyte-derived dendritic cells (moDC) progeny was increased by approximately twofold compared to untreated mice. In agreement, by in vivo quantitative imaging, we observed that treatment increased the number of LysM-EGFP cells traveling in tumor blood vessels and doubled the densities of both infiltrated LysM-EGFP monocytes and double-labeled EGFP/EYFP moDC. The treatment also led to an increased density of conventional cDCs2 subset together with a decrease of cDCs1 subset, necessary for the development of anti-tumor immunity. Finally, we describe differential spatial cell distributions and two immune cell-traveling routes into the brain. LysM-EGFP cells distributed as a gradient from the meninges towards the tumor whereas CD11c-EYFP/MHCII+ cells were located in the basal area of the tumor. Brain clearing also revealed a flow of CD11c-EYFP cells following the corpus callosum.

Conclusion
We uncovered new features in the dynamics of innate immune cells in GBM-bearing mice and deciphered precisely the key populations, i.e., DC subsets controlling immune responses, that are affected by VEGF blockade. Since despite differences, human pathogenesis presents similarities with our mouse model, the data provide new insights into the effect of bevacizumab at the cellular level.
Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat
Authors: Borjini Nozha , Sivilia Sandra , Giuliani Alessandro , Fernandez Mercedes , Giardino Luciana , Facchinetti Fabrizio , Calzà Laura 
Published: October 2019

AbstractBackgroundHypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies.MethodsIn order to identify potential biomarkers for early inflammatory and neurodegenerative events after neonatal hypoxia-ischemia, both male and female Wistar rat pups at postnatal day 7 (P7) were used and had their right carotid artery permanently doubly occluded and exposed to 8% oxygen for 90 min. Sensory and cognitive parameters were assessed by open field, rotarod, CatWalk, and Morris water maze (MWM) test. Plasma and CSF biomarkers were investigated on the acute (24 h and 72 h) and chronic phase (4 weeks). Brains were assessed for gene expression analysis by quantitative RT-PCR Array.ResultsWe found a delay of neurological reflex maturation in HI rats. We observed anxiolytic-like baseline behavior in males more than females following HI injury. HI rats held on the rotarod for a shorter time comparing to sham. HI injury impaired spatial learning ability on MWM test. The CatWalk assessment demonstrated a long-term deficit in gait parameters related to the hind paw. Proinflammatory biomarkers such as IL-6 in plasma and CCL2 and TNF-α in CSF showed an upregulation at 24 h after HI while other cytokines, such as IL-17A and CCL5, were upregulated after 72 h in CSF. At 24 h post-injury, we observed an increase of Edn1, Hif1-α, and Mmp9 mRNA levels in the ipsilateral vs the contralateral hemisphere of HI rats. An upregulation of genes involved with clotting and hematopoietic processes was observed 72 h post-injury.ConclusionsOur work showed that, in the immature brain, the HI injury induced an early increased production of several proinflammatory mediators detectable in plasma and CSF, followed by tissue damage in the hypoxic hemisphere and short-term as well as long-lasting neurobehavioral deficits.
Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice
Authors: Dekkers Susan , Wagner James G. , Vandebriel Rob J. , Eldridge Elyse A. , Tang Selina V. Y. , Miller Mark R. , Römer Isabella , de Jong Wim H. , Harkema Jack R. , Cassee Flemming R. 
Published: October 2019

Abstract

Background
Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. However, the influence of the different physicochemical properties of these particles on their adjuvant properties is largely unknown. Here we investigate the effects of chemical composition and redox activity of poorly soluble NPs on their adjuvant potency in a mouse model of airway hypersensitivity.

Results
NPs of roughly similar sizes with different chemical composition and redox activity, including CeO2, Zr-doped CeO2, Co3O4, Fe-doped Co3O4(using Fe2O3 or Fe3O4) and TiO2 NPs, all showed adjuvant activity. OVA induced immune responses following intranasal exposure of BALB/c mice to 0.02% OVA in combination with 200 μg NPs during sensitization (on day 1, 3, 6 and 8) and 0.5% OVA only during challenge (day 22, 23 and 24) were more pronounced compared to the same OVA treatment regime without NPs. Changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and eosinophil density in the conducting airways were observed. Adjuvant activity of the CeO2 NPs was primarily mediated via the Th2 response, while that of the Co3O4 NPs was characterised by no or less marked increases in IgE plasma levels, BALF IL-4 and IL-5 concentrations and percentages of eosinophils in BALF and more pronounced increases in BALF IL-6 concentrations and percentages of lymphocytes in BALF. Co-exposure to Co3O4 NPs with OVA and subsequent OVA challenge also induced perivascular and peribronchiolar lymphoid cell accumulation and formation of ectopic lymphoid tissue in lungs. Responses to OVA combined with various NPs were not affected by the amount of doping or redox activity of the NPs.

Conclusions
The findings indicate that chemical composition of NPs influences both the relative potency of NPs to exacerbate allergic airway sensitization and the type of immune response. However, no relation between the acellular redox activity and the observed adjuvant activity of the different NPs was found. Further research is needed to pinpoint the precise physiological properties of NPs and biological mechanisms determining adjuvant activity in order to facilitate a safe-by-design approach to NP development.
Morbidity and mortality of serious gastrointestinal complications after lung transplantation
Authors: Zevallos-Villegas Annette , Alonso-Moralejo Rodrigo , Cambra Félix , Hermida-Anchuelo Ana , Pérez-González Virginia , Gámez-García Pablo , Sayas-Catalán Javier , De Pablo- Gafas Alicia 
Published: October 2019

Abstract

Background
Gastrointestinal complications after lung transplatation are associated with an increased risk of morbidity and mortality. This study aims to describe severe gastrointestinal complications (SGC) after lung transplantation.

Methods
We performed a prospective, observational study that included 136 lung transplant patients during a seven year period in a tertiary care universitary hospital. SGC were defined as any diagnosis related to the gastrointestinal or biliary tract leading to lower survival rates or an invasive therapeutic procedure. Early and late complications were defined as those occurring < 30 days and ≥ 30 days post-transplant. The survival function was calculated through the Kaplan-Meier estimator. Variables were analyzed using univariate and multivariate analysis. Statistical significance was defined as p < 0.05.

Results
There were 17 (12.5%) SGC in 17 patients. Five were defined as early. Twelve patients (70.6%) required surgical treatment. Mortality was 52.9% (n = 9). Patients with SGC had a lower overall survival rate compared to those who did not (14 vs 28 months, p = 0.0099). The development of arrhythmias in the first 48 h of transplantation was a risk factor for gastrointestinal complications (p = 0.0326).

Conclusions
SGC are common after lung transplantation and are associated with a considerable increase in morbidity-mortality. Early recognition is necessary to avoid delays in treatment, since a clear predictor has not been found in order to forecast this relevant comorbidity.
Growth characteristics and therapeutic decision markers in von Hippel-Lindau disease patients with renal cell carcinoma
Authors: Schuhmacher Patrick , Kim Emily , Hahn Felix , Sekula Peggy , Jilg Cordula Annette , Leiber Christian , Neumann Hartmut P. , Schultze-Seemann Wolfgang , Walz Gerd , Zschiedrich Stefan 
Published: October 2019

Abstract

Background
Von Hippel-Lindau (VHL) disease is a multi-systemic hereditary disease associated with several benign and malignant tumor entities, including clear cell renal cell carcinoma (ccRCC). Since ccRCCs grow slowly, nephron sparing surgery is typically performed at a tumor diameter of 3–4 cm before the tumor metastasizes. However, in the case of recurrent disease, repeated surgical intervention can impair renal function. Therefore, it is crucial to optimize the timing for surgical interventions through a better understanding of the growth kinetics of ccRCCs in VHL. We investigated tumor growth kinetics and modern volumetric assessment to guide future therapeutic decisions.

Results
The prevalence of ccRCC was 28% in a cohort of 510 VHL patients. Of 144 patients with ccRCC, 41 were followed with serial imaging which identified 102 renal tumors, which exhibited heterogeneous growth kinetics. ccRCCs grew at an average absolute growth rate of 0.287 cm/year, an average relative growth rate [(lnV1-lnV0)/(t1-t0)] of 0.42% and an average volume doubling time of 27.15 months. Women had a faster relative growth rate than men. Age and specific mutations did not influence tumor growth. Because of the tumor heterogeneity, we developed an additional cut-off volume of 40 cm3 for surgical intervention.

Conclusions
Tumor heterogeneity and differences in growth kinetics is suggestive of a state of transient tumor dormancy in ccRCCs of VHL patients. The relative growth rate has not been previously described in other studies. Volumetric assessment as an additional parameter for surgical intervention could be a useful clinical tool and needs further investigation.