bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sampling and processing blood samples within the South American Youth/Child cARdiovascular and Environmental (SAYCARE) Study
Authors: López Graciela , Assali Serruya Raphael , Barchuk Magalí , Gaitan-Charry Diego , Torres-Leal Francisco Leonardo , Moreno Luis Alberto , Delgado Carlos Alberto , Barbosa Carvalho Heráclito , De Moraes Augusto César Ferreira , Berg Gabriela 
Published: January 2020

AbstractObesity and overweight in children and adolescents is increasing rapidly worldwide; however, scarce data have been reported from South America countries. With the purpose of assessing hyperlipidemia, insulin resistance and chronic inflammation, the evaluation of blood biomarkers such as glucose, lipoproteins and chronic inflammation proteins is required. In the context of the SAYCARE study, in children and adolescents (3 to 18 years) from seven South American cities, our aim was to assess the impact of pre analytical conditions on different biomarkers evaluated in 474 fresh serum samples, in different country centers. We also evaluated the stability according to time and frozen storage within this study across the concordance of the results obtained from the 49 blood samples measured in three different centers. Significant correlations as well as concordance were observed in TG, Total-C, HDL-C and glucose between Buenos Aires and São Paulo. The samples evaluated in Teresina and São Paulo presented similar results, with exception of total cholesterol. We observed acceptable concordance between Buenos Aires vs São Paulo and Teresina vs São Paulo, suggesting that samples could be processed in each of these centers. This concordance is a consequence of the strict pre analytical conditions previously established in the SAYCARE study.
Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1
Authors: Choi Jihye , Yoon Yi Na , Kim Nawon , Park Chan Sub , Seol Hyesil , Park In-Chul , Kim Hyun-Ah , Noh Woo Chul , Kim Jae-Sung , Seong Min-Ki 
Published: January 2020

AbstractEmerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we evaluated the association of p-S6K1 expression with radio-resistance in breast cancer cell lines and patients. During median follow-up of 33 (range, 0.1–111) months for 1770 primary breast cancer patients who underwent surgery, patients expressing p-S6K1 showed worse 10-year loco-regional recurrence-free survival (LRFS) compared to that of p-S6K1-negative patients after radiotherapy (93.4% vs. 97.7%, p = 0.015). Multivariate analysis revealed p-S6K1 expression as a predictor of radio-resistance (hazard ratio 7.9, 95% confidence interval 1.1–58.5, p = 0.04). In vitro, CD44high/CD24low MCF7 cells with a radioresistant phenotype expressed higher levels of p-S6K1 than control MCF7 cells. Furthermore, the combination of radiation with treatment of everolimus, an mTOR-S6K1 pathway inhibitor, sensitised CD44high/CD24low MCF7 cells to a greater extent than MCF7 cells. This study provides in vivo and in vitro evidence for p-S6K1 expression status as an important marker for predicting the resistance to radiotherapy and as a possible target for radio-sensitization in breast cancer patients.
Novel invasion indices quantify the feed-forward facilitation of tumor invasion by macrophages
Authors: Lim Gippeum J. , Kang Suk-Jo , Lee Ji Youn 
Published: January 2020

AbstractQuantitative and reliable measurement of cellular invasion is important to understand a range of biological processes such as cancer metastasis and angiogenesis. Spheroid invasion assays are an attractive in vitro platform because they effectively mimic the tumor cell invasion of solid tissues. Here, we developed an image analysis–based method to quantify the invasiveness of HT1080 human fibrosarcoma tumor cell spheroids. We segmented a cell-covered area into three subareas using objectively set threshold pixel intensities and calculated invasion indices using these subareas. Comparison with conventional parameters for spheroid invasion assays, such as area, length, and detached cells, showed that our indices present the invasion event at an early time and without being convoluted by proliferation. As an application, we then examined paracrine interactions between LLC1 mouse lung carcinoma cells and Raw264.7 mouse macrophage cells with our developed analysis method. We found that the invasion of tumor spheroids was increased by a macrophage-conditioned medium, concomitantly with a decrease in tumor cell proliferation. Importantly, invasion was further enhanced by a conditioned medium from activated macrophages by co-culture with tumor cells. Thus, our indices reveal that tumor cell invasion is facilitated in a feed-forward manner by communication between tumor cells and macrophages in the tumor microenvironment.
TAK-242 ameliorates contact dermatitis exacerbated by IL-36 receptor antagonist deficiency
Authors: Fukushima Hidehiko , Iwata Yohei , Watanabe Soichiro , Saito Kenta , Tanaka Yoshihito , Hasegawa Yurie , Akiyama Masashi , Sugiura Kazumitsu 
Published: January 2020

AbstractLoss-of-function mutations in IL36RN cause generalized pustular psoriasis (GPP), which is characterized by neutrophil-infiltrated lesions. Neutrophils are important during contact hypersensitivity in mice. However, it has never been determined whether interleukin-36 receptor antagonist (IL-36Ra) deficiency is an exacerbating factor in contact dermatitis. We examined whether a loss-of-function IL36RN mutation exacerbates contact dermatitis and evaluated the changes in contact dermatitis-related cytokines. Wild-type and Il36rn−/− mice were treated with 1-fluoro-2,4-dinitorobenzene (DNFB) and evaluated for ear thickness, histopathological features, numbers of infiltrated neutrophils, and numbers of CD4 + and CD8 + T cells. Furthermore, mRNA levels of contact dermatitis-related cytokines were measured by real-time polymerase chain reaction, and effects of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, on the contact hypersensitivity (CHS) response were evaluated. We found that the ear thickness, cytokine expression, and neutrophil infiltration significantly increased in Il36rn−/− mice compared with that in wild-type mice. TAK-242 alleviated CHS and prevented neutrophil infiltration, cytokine expression, and ear thickening in Il36rn−/− mice. These data indicate that Il36rn−/− mutations are an exacerbating factor for CHS and that TAK-242 can reduce the inflammatory responses that are associated with the CHS response.
Property Variation in Wavelength-thick Epsilon-Near-Zero ITO Metafilm for Near IR Photonic Devices
Authors: Ni Jimmy H. , Sarney Wendy L. , Leff Asher C. , Cahill James P. , Zhou Weimin 
Published: January 2020

AbstractThin indium tin oxide (ITO) films have been used as a medium to investigate epsilon-near-zero (ENZ) behavior for unconventional tailoring and manipulation of the light-matter interaction. However, the ENZ wavelength regime has not been studied carefully for ITO films with thicknesses larger than the wavelength. Thick ENZ ITO film would enable the development of a new family of ENZ-based opto-electronic devices that take full advantage of the ENZ behavior. Here, we demonstrated wavelength-thick ITO films reaching the ENZ regime around a wavelength of 1550 nm, which permit the design of such devices operating in the common optical telecommunications wavelength band. We discovered that the permittivity of the film was non-uniform with respect to the growth direction. In particular, after annealing at a sufficiently high temperature, the real part of the permittivity showed a step change from negative to positive value, crossing zero permittivity near the middle of the film. Subsequently, we conducted comprehensive microanalysis with X-ray diffraction, transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) to investigate the correlation of the permittivity variation with variations in the ITO crystallite morphology and relative concentrations of different atom species. The result of this study will allow us to design a new family of opto-electronic devices where ITO can be used as the cladding that guides light within an air-core waveguide to provide a new platform to explore ENZ properties such as environment insensitivity, super-coupling, and surface avoidance. We have also provided a comprehensive method to determine the permittivity in a non-uniform ENZ material by using an advanced physical model to the fit experimental data.
The role of Human leukocyte antigen class I on patient survival in Gastrointestinal cancers: a systematic review and meta- analysis
Authors: Najafimehr Hadis , Hajizadeh Nastaran , Nazemalhosseini-Mojarad Ehsan , Pourhoseingholi Mohamad Amin , Abdollahpour-Alitappeh Meghdad , Ashtari Sara , Zali Mohammad Reza 
Published: January 2020

AbstractThe prognostic role of Human leukocyte antigen class I (HLA- I) in gastrointestinal cancers has been remained controversial. We performed a meta-analysis to determine the role of classical HLA-I in predicting survival of patients. In addition, the relationship between HLA- I and some clinicopathological factors was evaluated. Published studies investigated HLA-I expression effect on gastrointestinal cancers were evaluated to determine association between HLA- I and overall survival (OS) and recurrence-free survival (RFS) in patients. The used effect sizes were hazard ratio (HR) and Odds ratio (OR) with 95% confidence interval (CI). A total of ten studies included 1307 patients were analyzed. The pooled results revealed that HLA- I overexpression was positively related to OS (HR: 0.72; 95% CI: 0.53–0.96) and demonstrated little association for RFS (HR: 0.70; 95% CI: 0.46–1.08). HLA-I overexpression is negative associated with poorer differentiation of tumor (OR: 0.53; 95% CI (0.43–0.81) and also higher stages of cancer (OR: 0.29; 95% CI (0.13–0.64). HLA- I overexpression was related to a better prognosis on OS and probably had little impact on RFS.
The Asthma-associated PER1-like domain-containing protein 1 (PERLD1) Haplotype Influences Soluble Glycosylphosphatidylinositol Anchor Protein (sGPI-AP) Levels in Serum and Immune Cell Proliferation
Authors: Sio Yang Yie , Anantharaman Ramani , Lee Sean Qiu En , Matta Sri Anusha , Ng Yu Ting , Chew Fook Tim 
Published: January 2020

AbstractPost-glycosylphosphatidylinositol (GPI) attachment to proteins 3, also known as PGAP3 or PERLD1 (PER1-like domain-containing protein 1), participates in the lipid remodeling process of glycosylphosphatidylinositol (GPI) anchor proteins during post-translational modification. Functional defect in PERLD1 was previously hypothesized to influence this process in T-cells and their subsequent activation and proliferation. This current study aims to functionally characterize PERLD1 genetic variants and relate this with human immune cells proliferation rate upon stimulation. We first showed the association between a PERLD1 tag-single nucleotide polymorphism (tagSNP), rs2941504, and the development of asthma in our study population. This association remained significant after conditioning for the other asthma-associated SNP rs8076131 that is also located within the 17q12–21 region. Subsequent sequencing of 40 unrelated Singapore Chinese individuals identified 12 more common PERLD1 SNPs (minor allele frequency > 5%) that are in linkage disequilibrium (LD, r2 > 0.8) with rs2941504. Through in vitro studies, 7 of these SNPs were found to form a functional haplotype that influences alternative splicing of PERLD1 transcript. This result was validated in human peripheral blood mononuclear cell (PBMC), where the minor haplotype (Hap2) was shown to be associated with significantly increased PERLD1 truncated transcript. Additionally, Hap2 was found to be related to increased levels of several soluble GPI-anchored proteins (such as sCD55 and sCD59) in serum. Elevated sCD55 in the serum was demonstrated to reduce the proliferation rate of PBMCs upon phytohaemagglutinin (PHA) stimulation. Taken together, the current study has shown a functional PERLD1 haplotype, which modifies PBMC sensitivity upon stimulation and may contribute to the individual’s susceptibility to allergic asthma.
Factors that influence the complications and outcomes of femoral neck fractures treated by cannulated screw fixation
Authors: Ramadanov Nikolai , Toma Ionel , Herkner Harald , Klein Roman , Behringer Wilhelm , Matthes Gerrit 
Published: January 2020

AbstractTo investigate the influence of various factors on the two outcome parameters “procedure - specific complication” (femoral head necrosis, infection, nonunion, femoral neck shortening, screw loosening, implant penetration) and “functional outcome” in patients with displaced and undisplaced femoral neck fracture treated by cannulated screw fixation. All cases of a femoral neck fracture, operated by cannulated screw fixation, in the period from December 2014 to December 2017 were included. The observation period of the included patients was 12 months. Information on their outcome was collected after evaluation of current x-ray images and on request from the responsible further treatment physician. Continuous data were presented as mean value ± standard deviation, categorical data as absolute and relative frequency. The effect of potential factors on endpoints was estimated with a multivariable logistic regression analysis and 95% confidence intervals calculated. The null hypothesis Odds Ratio = 1 was checked by the Wald test. The likelihood ratio test was used to test for deviation from linearity. The mean age of the 56 included patients was 72 years (36 min, 96 max), 44.5% (n = 25) were male and 55.5% (n = 25) female. The femoral neck fractures were classified as follows: Garden I: 73%, Garden II: 16%, Garden III: 11%, Pauwels I: 73%, Pauwels II: 21%, Pauwels III: 5%, 31-B1: 73%, 31-B2: 27%, 31-B3: 0%. The factor patient age showed a statistically significant influence on the outcome parameter procedure-specific complication. None of the remaining factors examined showed a statistically significant influence on both outcome parameters procedure-specific complication and functional outcome. 69% of the patients from age 80 onwards suffered a procedure-specific complication. A rate of 41% procedure-specific complications as an outcome parameter in trauma surgery shows a necessity for improvement. The increasing risk of procedure-specific complications for patients with a femoral neck fracture treated by cannulated screw fixation is associated with rising patient age. A more stable head-perserving operative method or an endoprosthetic procedure should be considered in high-risk patients (≥80 y.o.).
Impact of fullerol C60(OH)24 nanoparticles on the production of emerging toxins by Aspergillus flavus
Authors: Kovač Tihomir , Borišev Ivana , Kovač Marija , Lončarić Ante , Čačić Kenjerić Frane , Djordjevic Aleksandar , Strelec Ivica , Ezekiel Chibundu N. , Sulyok Michael , Krska Rudolf , Šarkanj Bojan 
Published: January 2020

AbstractThe impact of fullerene C60 water soluble daughter molecules - fullerols C60(OH)24 nanoparticles (FNP) on emerging (non-aflatoxin biosynthetic pathway) toxins production in mycelia and yeast extract sucrose (YES) media of A. flavus was investigated under growth conditions of 29 °C in the dark for a 168 h period. The FNP solution (10, 100 and 1000 ng mL−1) contained predominantly nanoparticles of 8 nm diameter and with zeta potential mean value of −33 mV. Ten emerging metabolites were produced at concentrations reaching 1,745,035 ng 50 mL−1 YES medium. Seven of the metabolites were found in mycelia and media, while three were only in mycelia. Majority of the metabolites were detected in higher quantity in mycelia than in media, at a ratio of 99:1 (m/m). However, higher metabolite quantities were found in media following FNP application, while FNP caused a decrease of total metabolite quantities in mycelia. The concentrations of the metabolites in media increased in the presence of 1000 ng mL−1 FNP while mycelial quantities of the metabolites decreased with increased applied FNP dose. The impacts of global climate changes on FNP availability in the environment and on mycotoxin occurrence in crops increase the relevance of this study for risk assessment of nanoparticles. Cordycepin is reported for the first time as metabolite of A. flavus.
SLA-1 Genetic Diversity in Pigs: Extensive Analysis of Copy Number Variation, Heterozygosity, Expression, and Breed Specificity
Authors: Le Minh Thong , Choi Hojun , Lee Hyejeong , Le Van Chanh Quy , Ahn Byeongyong , Ho Chak-Sum , Hong Kwonho , Song Hyuk , Kim Jin-Hoi , Park Chankyu 
Published: January 2020

AbstractSwine leukocyte antigens play indispensable roles in immune responses by recognizing a large number of foreign antigens and thus, their genetic diversity plays a critical role in their functions. In this study, we developed a new high-resolution typing method for pig SLA-1 and successfully typed 307 individuals from diverse genetic backgrounds including 11 pure breeds, 1 cross bred, and 12 cell lines. We identified a total of 52 alleles including 18 novel alleles and 9 SLA-1 duplication haplotypes, including 4 new haplotypes. We observed significant differences in the distribution of SLA-1 alleles among the different pig breeds, including the breed specific alleles. SLA-1 duplication was observed in 33% of the chromosomes and was especially high in the biomedical model breeds such as SNU (100%) and NIH (76%) miniature pigs. Our analysis showed that SLA-1 duplication is associated with the increased level of SLA-1 mRNA expression in porcine cells compared to that of the single copy haplotype. Therefore, we provide here the results of the most extensive genetic analysis on pig SLA-1.
The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells
Authors: Rahman Md Shaifur , Wruck Wasco , Spitzhorn Lucas-Sebastian , Nguyen Lisa , Bohndorf Martina , Martins Soraia , Asar Fatima , Ncube Audrey , Erichsen Lars , Graffmann Nina , Adjaye James 
Published: January 2020

AbstractHuman urine is a non-invasive source of renal stem cells with regeneration potential. Urine-derived renal progenitor cells were isolated from 10 individuals of both genders and distinct ages. These renal progenitors express pluripotency-associated proteins- TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133, as well as the renal stem cell markers -SIX2, CITED1, WT1, CD24 and CD106. The transcriptomes of all SIX2+ renal progenitors clustered together, and distinct from the human kidney biopsy-derived epithelial proximal cells (hREPCs). Stimulation of the urine-derived renal progenitor cells (UdRPCs) with the GSK3β-inhibitor (CHIR99021) induced differentiation. Transcriptome and KEGG pathway analysis revealed upregulation of WNT-associated genes- AXIN2, JUN and NKD1. Protein interaction network identified JUN- a downstream target of the WNT pathway in association with STAT3, ATF2 and MAPK1 as a putative negative regulator of self-renewal. Furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway. The urine-derived renal progenitor cells and the data presented should lay the foundation for studying nephrogenesis in human.
Association of Insulin-like Growth Factor 1 Concentrations with Risk for and Prognosis of Amyotrophic Lateral Sclerosis – Results from the ALS Registry Swabia
Authors: Nagel Gabriele , Peter Raphael S. , Rosenbohm Angela , Koenig Wolfgang , Dupuis Luc , Rothenbacher Dietrich , Ludolph Albert C. 
Published: January 2020

AbstractWe investigated the associations of serum concentration of insulin-like growth factor 1 (IGF1) with risk and prognosis of ALS in the ALS registry (October 2010–June 2014, median follow-up 67.6 months) in a case-control and cohort study, respectively. Serum samples were measured for IGF-1. Information on covariates was collected by standardized questionnaire. We applied conditional logistic regression to appraise the risk and Cox proportional hazards models to appraise the prognostic value of IGF-1. Data of 294 ALS patients (mean age 65.4 (SD 11.0) years, 60.2% men) and 504 controls were included in the case-control study. Median serum IGF-1 concentrations were slightly higher in ALS cases than in controls (101 vs. 99.5 ng/ml). IGF-1 concentrations were not associated with ALS risk in the fully adjusted model (top vs. bottom quartile: OR 1.16; 95%-CI 0.73–1.84, p for trend = 0.44). Among 293 ALS cases (mean age 65.5 (SD 10.5) years, 56.8% men) 243 died during follow-up. We found a statistically significant inverse association between continuous IGF-1 concentrations and survival (p = 0.01). Very high values IGF-1 were associated with a better prognosis of ALS suggesting that functions related to IGF-1 could be involved in survival.
CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual
Authors: Yun Yeomin , Hong Sung-Ah , Kim Ka-Kyung , Baek Daye , Lee Dongsu , Londhe Ashwini M. , Lee Minhyung , Yu Jihyeon , McEachin Zachary T. , Bassell Gary J. , Bowser Robert , Hales Chadwick M. , Cho Sung-Rae , Kim Janghwan , Pae Ae Nim , Cheong Eunji , Kim Sangwoo , Boulis Nicholas M. , Bae Sangsu , Ha Yoon 
Published: January 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. Here we compared whole genome sequencing results from a male ALS patient and his healthy parents to identify relevant variants, and chose one variant in the X-linked ATP7A gene, M1311V, as a strong disease-linked candidate after profound examination. Although this variant is not rare in the Ashkenazi Jewish population according to results in the genome aggregation database (gnomAD), CRISPR-mediated gene correction of this mutation in patient-derived and re-differentiated motor neurons drastically rescued neuronal activities and functions. These results suggest that the ATP7A M1311V mutation has a potential responsibility for ALS in this patient and might be a potential therapeutic target, revealed here by a personalized medicine strategy.
Glucose-induced microRNA-218 suppresses the proliferation and promotes the apoptosis of human retinal pigment epithelium cells by targeting RUNX2
Authors: Yao Rui , Yao Xiaoxi , Liu Ru , Peng Jingli , Tian Tao 
Published: January 2020

Abstract
Objective: MicroRNA-218 (miR-218) critical for preventing the progression of numerous diseases, including diseases of the retinal pigment epithelium (RPE). However, the mechanism by which miR-218 regulates the PRE in humans remains largely unknown. Our study investigated the effects of glucose-induced miR-218 expression on human RPE cells (ARPE-19), as well as its targeted regulatory effect.
Methods: The levels of miR-218 and runt-related transcription factor 2 (RUNX2) expression were investigated by RT-qPCR or Western blot assays. Cell viability and apoptosis were assessed by CCK-8 assays, flow cytometry, and Hoechst staining. A luciferase reporter assay was performed to determine whether Runx2 is a target gene of miR-218.
Results: Our results showed that glucose up-regulated miR-218 expression, suppressed proliferation, and induced the apoptosis of ARPE-19 cells. We verified that miR-218 could inhibit the proliferation and facilitate the apoptosis of ARPE-19 cells, while inhibition of miR-218 expression produced the opposite effects. In terms of mechanism, we demonstrated that RUNX2 was a direct target of miR-218. Functional experiments showed that Runx2 served as a miR-218 target to help inhibit the proliferation and induction of apoptosis in ARPE-19 cells.
Conclusion: Our findings suggest the miR-218/Runx2 axis as a potential target for treating diabetic retinopathy (DR).