bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic nomogram of hypoxia-related genes predicting overall survival of colorectal cancer–Analysis of TCGA database
Authors: Lee Joon-Hyop , Jung Sohee , Park Won Seo , Choe Eun Kyung , Kim Eunyoung , Shin Rumi , Heo Seung Chul , Lee Jae Hyun , Kim Kwangsoo , Chai Young Jun 
Published: February 2019

AbstractHypoxia-related gene (HRG) expression is associated with survival outcomes of colorectal cancer (CRC). Our aim was developing a nomogram predicting CRC overall survival (OS) with HRGs and clinicopathological factors. The Cancer Genome Atlas (TCGA) database was used as discovery cohort and two Gene Expression Omnibus databases (GSE39582 and GSE41258) served as validation cohorts. A genetic risk score model prognosticating OS was developed using mRNA expression level of HRGs. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. The genetic risk score model included four HRGs (HSPA1L, PUM1, UBE2D2, and HSP27) and successfully prognosticated OS of discovery and two validation cohorts (p < 0.001 for TCGA discovery set, p < 0.003 for the GSE39582 and p = 0.042 for the GSE41258 datasets). Nomogram included genetic risk score, age, and TNM stage. Harrell’s concordance indexes of the nomogram were higher than those of TNM stage alone in the discovery set (0.77 vs. 0.69, p < 0.001), GSE39582 (0.65 vs. 0.63, p < 0.001), and GSE41258 datasets (0.78 vs. 0.77, p < 0.001). Our nomogram successfully predicted OS of CRC patients. The mRNA expression level of the HRGs might be useful as an ancillary marker for prognosticating CRC outcome.
Fibroblast growth factor receptor signaling in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Jerchel Isabel S. , Hoogkamer Alex Q. , Ariës Ingrid M. , Boer Judith M. , Besselink Nicolle J. M. , Koudijs Marco J. , Pieters Rob , den Boer Monique L. 
Published: February 2019

AbstractThe FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Here we investigate the effect of FGFR stimulation on pediatric BCP-ALL cells in vitro, and search for mutations with deep targeted next-generation sequencing of mutational hotspots in FGFR1, FGFR2, and FGFR3. In 481 primary BCP-ALL cases, 28 samples from 19 unique relapsed BCP-ALL cases, and twelve BCP-ALL cell lines we found that mutations are rare (4/481 = 0.8%, 0/28 and 0/12) and do not affect codons which are frequently mutated in other malignancies. However, recombinant ligand FGF2 reduced the response to prednisolone in several BCP-ALL cell lines in vitro. We therefore conclude that FGFR signaling can contribute to prednisolone resistance in BCP-ALL cells, but that activating mutations in this receptor tyrosine kinase family are very rare.
Epithelial Cells and Fibroblasts from the Human Female Reproductive Tract Accumulate and Release TFV and TAF to Sustain Inhibition of HIV Infection of CD4+ T cells
Authors: Shen Zheng , Rodriguez-Garcia Marta , Patel Mickey V. , Bodwell Jack , Wira Charles R. 
Published: February 2019

AbstractTenofovir (TFV) treatment of female reproductive tract (FRT) cells results in differential accumulation of intracellular Tenofovir diphosphate (TFV-DP) in different cell types, with greater concentrations in epithelial cells (100-fold) and fibroblasts (10-fold) than in CD4+ T cells. The possibility that TFV-DP accumulation and retention in epithelial cells and fibroblasts may alter TFV availability and protection of CD4+ T cells against HIV infection, prompted us to evaluate TFV and/or Tenofovir alafenamide (TAF) release from FRT cells. Endometrial, endocervical and ectocervical polarized epithelial cells and fibroblasts were pre-loaded with TFV or TAF, and secretions tested for their ability to inhibit HIV infection of activated blood CD4+ T cells. Epithelial cell basolateral secretions (1, 2 and 3 days post-loading), but not apical secretions, suppressed HIV infection of CD4+ T cells, as did secretions from pre-loaded fibroblasts from each site. Intracellular TFV-DP levels in epithelial cells following preloading with TFV or TAF correlated directly with ARV protection of CD4+ T cells from HIV infection. When added apically to epithelial cells, TFV/TAF was released basolaterally, in part through Multidrug Resistant Protein transporters, taken up by fibroblasts and released into secretions to partially protect CD4+ T cells. These findings demonstrate that epithelial cells and fibroblasts release TFV/TAF for use by CD4+ T cells and suggest that the tissue environment plays a major role in the sustained protection against HIV infection.
Permeability regain and aqueous phase migration during hydraulic fracturing shut-ins
Authors: Li Shuai , Lei Qun , Wang Xin , Cai Bo , Liu Guangfeng , Wang Long 
Published: February 2019

AbstractHydraulic fracturing has become a key technology to economically extract oil and gas from unconventional reservoirs. During hydraulic fracturing, fluid loss and water invasion into formation can cause serious permeability reduction near fracture face. At the same time, field practice also showed that well shut-ins after hydraulic fracturing could significantly increase hydrocarbon outputs, whereas the inner mechanism still remains unknown. In this paper, firstly, we studied permeability reduction after water invasion and permeability enhancement after well shut-ins using a core flooding system. Then, to investigate the inner mechanism, we studied aqueous phase migration during shut-ins using nuclear magnetic resonance (NMR) method. Results showed that fluids invasion reduce matrix permeability while well shut-ins can improve permeability and this improvement depends on the length of shut-ins time. NMR results showed that aqueous phases mainly distribute in macropores and mesopores after water invasion, while in shut-ins period, these invaded aqueous phases redistribute and migrate from larger pore spaces to smaller ones. Aqueous phase redistribution and migration during shut-ins period can remove near fracture water-block, reduce capillary discontinuity and increase the relative permeability of hydrocarbon phase, and this is the reason for permeability enhancement and hydrocarbon output increase after well shut-ins.
Development of a new High Resolution Melting (HRM) assay for identification and differentiation of Mycobacterium tuberculosis complex samples
Authors: Landolt Patricia , Stephan Roger , Scherrer Simone 
Published: February 2019

AbstractThe rapid identification and differentiation of members of the Mycobacterium tuberculosis complex (MTBC) is essential to assess the potential zoonotic risk. Different available molecular methods are time consuming since they depend on cultivation of mycobacteria. High Resolution Melting (HRM) is a low cost, rapid and easy to perform single-tube method not limited to cultured samples. In this study, a HRM assay specifically targeting gyrB was developed to simultaneously identify and differentiate Mycobacterium (M.) tuberculosis, M. microti and M. bovis/M. caprae. To evaluate the performance of this assay, 38 MTBC isolates and 25 directly extracted clinical specimens were analysed. HRM results of all 38 (100%) examined isolates correlated with the results obtained with the commercially available GenoType MTBC test (Hain Lifescience). From the 25 clinical specimens tested, species identification by HRM showed concordant results with the previously used identification methods in 23 samples (92%). The assay demonstrated a good analytical sensitivity, specificity and reproducibility and can be used directly on clinical specimens.
The Regenerative Potential of Amniotic Fluid Stem Cell Extracellular Vesicles: Lessons Learned by Comparing Different Isolation Techniques
Authors: Antounians Lina , Tzanetakis Areti , Pellerito Ornella , Catania Vincenzo D. , Sulistyo Adrienne , Montalva Louise , McVey Mark J. , Zani Augusto 
Published: February 2019

AbstractExtracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs) mediate anti-apoptotic, pro-angiogenic, and immune-modulatory effects in multiple disease models, such as skeletal muscle atrophy and Alport syndrome. A source of potential variability in EV biological functions is how EV are isolated from parent cells. Currently, a comparative study of different EV isolation strategies using conditioned medium from AFSCs is lacking. Herein, we examined different isolation strategies for AFSC-EVs, using common techniques based on differential sedimentation (ultracentrifugation), solubility (ExoQuick, Total Exosome Isolation Reagent, Exo-PREP), or size-exclusion chromatography (qEV). All techniques isolated AFSC-EVs with typical EV morphology and protein markers. In contrast, AFSC-EV size, protein content, and yield varied depending on the method of isolation. When equal volumes of the different AFSC-EV preparations were used as treatment in a model of lung epithelial injury, we observed a significant variation in how AFSC-EVs were able to protect against cell death. AFSC-EV enhancement of cell survival appeared to be dose dependent, and largely uninfluenced by variation in EV-size distributions, relative EV-purity, or their total protein content. The variation in EV-mediated cell survival obtained with different isolation strategies emphasizes the importance of testing alternative isolation techniques in order to maximize EV regenerative capacity.
Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals
Authors: Jang Hyemin , Kang Danbee , Chang Yoosoo , Kim Yeshin , Lee Jin San , Kim Ko Woon , Jang Young Kyoung , Kim Hee Jin , Na Duk L. , Shin Hee Young , Kang Mira , Guallar Eliseo , Cho Juhee , Seo Sang Won 
Published: February 2019

AbstractWe aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and cerebral small vessel disease (CSVD) burden, especially according to the NAFLD severity. A total of 1,260 participants were included. The CSVD burden was assessed with white matter hyperintensities (WMH), lacunes, and microbleeds (MBs) on brain MRI. An ultrasound diagnosis of fatty liver was made based on standard criteria, and the Fibrosis-4 (FIB-4) index was used to classify participants with NAFLD with having a high-intermediate (FIB-4 ≥1.45) or low (FIB-4 < 1.45) probability of advanced fibrosis. A multivariable logistic regression analysis was used to assess the association between NAFLD and the presence of moderate to severe WMH, lacunes, and MBs. NAFLD had a significant association only with moderate to severe WMH (OR: 1.64, 95% CI: 1.10–2.42), even after controlling for cardiometabolic risk factors. A linear trend test showed a significant association between the severity of NAFLD fibrosis and the presence of moderate to severe WMH (p for trend <0.001). Our findings suggest that NAFLD, especially NAFLD with fibrosis, has a significant association with the presence of moderate to severe WMH in cognitively normal individuals, and NAFLD severity predicted more frequent moderate to severe WMH.
In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds
Authors: Albanna Mohammed , Binder Kyle W. , Murphy Sean V. , Kim Jaehyun , Qasem Shadi A. , Zhao Weixin , Tan Josh , El-Amin Idris B. , Dice Dennis D. , Marco Julie , Green Jason , Xu Tao , Skardal Aleksander , Holmes James H. , Jackson John D. , Atala Anthony , Yoo James J. 
Published: February 2019

AbstractThe early treatment and rapid closure of acute or chronic wounds is essential for normal healing and prevention of hypertrophic scarring. The use of split thickness autografts is often limited by the availability of a suitable area of healthy donor skin to harvest. Cellular and non-cellular biological skin-equivalents are commonly used as an alternative treatment option for these patients, however these treatments usually involve multiple surgical procedures and associated with high costs of production and repeated wound treatment. Here we describe a novel design and a proof-of-concept validation of a mobile skin bioprinting system that provides rapid on-site management of extensive wounds. Integrated imaging technology facilitated the precise delivery of either autologous or allogeneic dermal fibroblasts and epidermal keratinocytes directly into an injured area, replicating the layered skin structure. Excisional wounds bioprinted with layered autologous dermal fibroblasts and epidermal keratinocytes in a hydrogel carrier showed rapid wound closure, reduced contraction and accelerated re-epithelialization. These regenerated tissues had a dermal structure and composition similar to healthy skin, with extensive collagen deposition arranged in large, organized fibers, extensive mature vascular formation and proliferating keratinocytes.
Solution of Cross-Kerr Interaction Combined with Parametric Amplification
Authors: Khorasani Sina 
Published: February 2019

AbstractWe present a full operator approach to treatment of the cross-Kerr interaction combined with parametric amplification. It is shown that this problem can be exactly integrated using the method of higher-order operators. While the initial basis is infinite-dimensional, an orthogonal transformation can reduce the problem exactly into a six-dimensional basis which can be integrated conveniently.
Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer
Authors: Martin Nikolas Tim , Roy Dominic Guy , Workenhe Samuel Tekeste , van den Wollenberg Diana J. M. , Hoeben Rob C. , Mossman Karen Louise , Bell John Cameron , Bourgeois-Daigneault Marie-Claude 
Published: February 2019

AbstractThe use of oncolytic viruses (OVs) for cancer treatment is emerging as a successful strategy that combines the direct, targeted killing of the cancer with the induction of a long-lasting anti-tumor immune response. Using multiple aggressive murine models of triple-negative breast cancer, we have recently demonstrated that the early administration of oncolytic Maraba virus (MRB) prior to surgical resection of the primary tumor is sufficient to minimize the metastatic burden, protect against tumor rechallenge, cure a fraction of the mice and sensitize refractory tumors to immune checkpoint blockade without the need for further treatment. Here, we apply our surgical model to other OVs: Vesicular stomatitis virus (VSV), Adenovirus (Ad), Reovirus (Reo) and Herpes simplex virus (HSV) and show that all of the tested OVs could positively change the outcome of the treated animals. The growth of the primary and secondary tumors was differently affected by the various OVs and most of the viruses conferred survival benefits in this neoadjuvant setting despite the absence of direct treatment following rechallenge. This study establishes that OV-therapy confers long-term protection when administered in the pre-operative window of opportunity.
Amplified Spontaneous Emission in Paper
Authors: Hoinka N. M. , Fuhrmann-Lieker T. 
Published: February 2019

AbstractIndustrially produced copy paper is presented as a novel optical material for narrow-band stimulated emission. Fluorescent brightening agents (FBA) such as Calcofluor White provide enough gain to exceed the threshold for amplified spontaneous emission. By applying an additional dye such as Coumarin 307, or simply a highlighter pen, the emission line can be shifted from blue (~440 nm), towards turquoise (>480 nm), up to orange (590 nm) which can be useful for spectroscopic applications. These properties are demonstrated in two papers, a commercial copy paper and a FBA-stained calligraphy paper.
Four-dimensional joint visualization of electrode degradation and liquid water distribution inside operating polymer electrolyte fuel cells
Authors: White Robin T. , Eberhardt Sebastian H. , Singh Yadvinder , Haddow Tylynn , Dutta Monica , Orfino Francesco P. , Kjeang Erik 
Published: February 2019

AbstractUnderstanding of degradation mechanisms present in polymer electrolyte fuel cells (PEFCs) is important to continue the integration of this clean energy technology into everyday life. Further comprehension of the interaction between various components during fuel cell operation is also critical in this context. In this work, a four-dimensional operando X-ray computed tomography method is developed for combined visualization of all PEFC components as well as transient water distribution residing in the cell, which results as a by-product of the electrochemical reaction. Time resolved, identical-location visualization through degradation stages is uniquely enabled by the non-invasive and non-destructive qualities of this method. By applying an accelerated stress test that targets cathode catalyst layer (CCL) corrosion, novel observations resulting from morphological changes of the CCL such as reduction in the water volume in the adjacent gas diffusion layer, CCL crack formation and propagation, membrane swelling, as well as quantification of local carbon loss is achieved. Additionally, insight into features that contribute to reduced fuel cell performance is enabled by the use of this specialized imaging technique, such as increased membrane undulation causing delamination and separation of the CCL from the microporous layer, which greatly affects liquid water pathways and overall device performance.
Revisit Population-based and Family-based Genotype Imputation
Authors: Liu Ching-Ti , Deng Xuan , Fisher Virginia , Heard-Costa Nancy , Xu Hanfei , Zhou Yanhua , Vasan Ramachandran S. , Cupples L. Adrienne 
Published: February 2019

AbstractGenome-Wide Association (GWA) with population-based imputation (PBI) has been successful in identifying common variants associated with complex diseases; however, much heritability remains to be explained and low frequency variants (LFV) may contribute. To identify LFV, a study of unrelated individuals may no longer be as efficient as a family study, where rare population variants can be frequent in families. Family-based imputation (FBI) provides an opportunity to evaluate LFV. To compare the performance of PBI and FBI, we conducted extensive simulations, generating genotypes using SeqSIMLA from various reference panels for families. We masked genotype information for variants unavailable in Framingham 550 K GWA genotype data in less informative subjects selected by GIGI-Pick. We implemented IMPUTE2 with duoHMM in SHAPEIT (Impute2_duoHMM) for PBI, MERLIN and GIGI for FBI and PedBLIMP for a hybrid approach. In general, FBI in both MERLIN and GIGI outperformed other approaches with imputation accuracy greater than 0.99 for the squared correlation and imputation quality scores (IQS) especially for LFV, although imputation accuracy from MERLIN depends on pedigree splitting for larger families. PBI performed worst with the exception of good imputation accuracy for common variants when a closely ancestry matched reference is used. In summary, linkage disequilibrium (LD) information from large available genotype resources provides good imputation for common variants with well-selected reference panels without requiring densely sequenced data in family members, while imputation of LFV with FBI benefits more from information on inheritance patterns within families yielding better imputation.
Fractal conceptualization of intumescent fire barriers, toward simulations of virtual morphologies
Authors: Okyay Gizem , Naik Anil D. , Samyn Fabienne , Jimenez Maude , Bourbigot Serge 
Published: February 2019

AbstractBy limiting the heat spread during a fire hazard, intumescent coatings are important components of passive protection systems. They swell due to heat induced reactions of micro constituents and are transformed into carbonaceous porous-like media, known as intumescent chars. Their multiscale inner structures, key elements of performance, are costly to predict by recurrent and large scale fire testing while numerical simulations are challenging due to complex kinetics. Hence, we propose a novel approach using the fractal theory and the random nature of events to conceptualize the coating expansion. Experimental specimens were obtained from fire protective coatings exposed to bench scale hydrocarbon fire. Mass fractals were evidenced in the slices of 3D sample volumes reconstructed from X-ray microtomography. Consequently, geometrical building blocks were simulated by random walk, active walk, aggregation-like and site percolation: physical-chemical modes of action were inherent in the attribution of the randomness. It is a first demonstration to conceptualize different types of intumescent actions by a generalized approach with dimensionless parameters at multiscale, thus eliminating the simulation of complex kinetics to obtain a realistic morphology. Also, fractal results brought new evidence to former chemical analyses on fire test residues trying to explain the kinetics of expansion. Expected outcomes are to predict virtually the reaction of fire protective systems hence to speed-up the assessment of fire performance through computed properties of virtual volumes.
Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease
Authors: Dosh Rasha H. , Jordan-Mahy Nicola , Sammon Christopher , Le Maitre Christine L. 
Published: February 2019

AbstractThein vitrostudy of the pathogenesis of inflammatory bowel disease (IBD) requires a cell model which closely reflects the characteristics of thein vivointestinal epithelium. This study aimed to investigate the application of L-pNIPAM hydrogel as a scaffold to develop a long-term 3D co-culture model of Caco-2 and HT29-MTX cells under conditions analogous to inflammation, to determine its potential use in studying IBD. Monocultures and co-cultures were layered on L-pNIPAM hydrogel scaffolds and maintained under dynamic culture conditions for up to 12 weeks. Treatments with IL-1β, TNFα, and hypoxia for 1 week were used to create an inflammatory environment. Following prolonged culture, the metabolic activity of Caco-2 monoculture and 90% Caco-2/10% HT29-MTX co-cultures on L-pNIPAM hydrogels were increased, and finger-like structures, similar in appearance to villi were observed. Following treatment with IL-1β, TNFα and hypoxia, ALP and ZO-1 were decreased, MUC2 increased, and MUC5AC remained unchanged. ADAMTS1 was increased in response to hypoxia. Caspase 3 expression was increased in response to TNFα and hypoxic conditions. In conclusion, L-pNIPAM hydrogel supported long-term co-culture within a 3D model. Furthermore, stimulation with factors seen during inflammation recapitulated features seen during IBD.