bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of surgical resection before palliative chemotherapy in advanced gastric cancer
Authors: Choi Yong Won , Ahn Mi Sun , Jeong Geum Sook , Lee Hyun Woo , Jeong Seong Hyun , Kang Seok Yun , Park Joon Seong , Choi Jin-Hyuk , Son Sang-Yong , Hur Hoon , Han Sang-Uk , Sheen Seung Soo 
Published: March 2019

AbstractThe role of palliative surgical resection in recurrent or metastatic gastric cancer is still controversial. A retrospective review was conducted on 689 patients who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 382) gastric cancer. Among 131 patients (89 primary metastatic and 42 recurrent) with surgical resection before chemotherpay, 75 underwent gastrectomy, 42 metastasectomy, and 14 gastrectomy with metastasectomy. The median overall survival (OS) of patients who underwent surgical resection was significantly longer than that of patients who received chemotherapy alone (18 vs. 9 months, p < 0.0001). The OS benefit of surgical resection was consistent across subgroups. In multivariate analysis, surgical resection was independently associated with favorable OS (hazard ratio = 0.42, p < 0.0001). Moreover, patients with surgical resection showed favorable OS both in univariate (p < 0.0001) and multivariate (p < 0.0001) analysis even after propensity score matching. In addition, the median OS of patients who underwent gross complete resection (n = 54) was significantly longer than that of patients who underwent incomplete resection (n = 77) (30 vs. 15 months, p = 0.002). The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer patients may result in a favorable outcome, especially when complete resection is achievable.
Conversion of tectonic and climatic forcings into records of sediment supply and provenance
Authors: Sharman Glenn R. , Sylvester Zoltan , Covault Jacob A. 
Published: March 2019

AbstractUnderstanding how environmental forcings (e.g., tectonics, climate) are transformed by erosional landscapes into sedimentary signals is a critical component of inverting the stratigraphic record. Previous research has largely focused on sediment supply (Qs) and grain size as the de facto sedimentary signals of changing forcing mechanisms. We use a numerical model to consider the paired response of sediment provenance (Pv), expressed as fractional sediment load, andQsto demonstrate that the same change in environmental forcing may have a different expression in the sedimentary record. WhileQsreflects integrated denudation across an erosional catchment,Pvis controlled by spatially variable erosion that occurs in transient landscapes.Pvfrom proximal sediment sources increases during upstream knickpoint migration, whereasPvfrom distal sediment sources increases when bedrock channels incise to produce lower gradient profiles. Differences between theQsandPvsignals relate to distinct geomorphic processes that operate on different time scales and allow for a refined differentiation of the timing and mechanism of forcings than possible via analysis of either signal alone. Future efforts to integrate multiple sedimentary signals may thus yield a richer picture of underlying forcing mechanisms, facilitating efforts to invert the stratigraphic record.
Toxic aldehyde generation in and food uptake from culinary oils during frying practices: peroxidative resistance of a monounsaturate-rich algae oil
Authors: Moumtaz Sarah , Percival Benita C. , Parmar Devki , Grootveld Kerry L. , Jansson Pim , Grootveld Martin 
Published: March 2019

AbstractHuman ingestion of cytotoxic and genotoxic aldehydes potentially induces deleterious health effects, and high concentrations of these secondary lipid oxidation products (LOPs) are generated in polyunsaturated fatty acid (PUFA)-rich culinary oils during high temperature frying practices. Here, we explored the peroxidative resistance of a novel monounsaturate-rich algae frying oil (MRAFO) during laboratory-simulated shallow- and domestically-based repetitive deep-frying episodes (LSSFEs and DBRDFEs respectively), the latter featuring potato chip fryings. Culinary frying oils underwent LSSFEs at 180 °C, and DBRDFEs at 170 °C: aldehydes were determined by1H NMR analysis in samples collected at increasing heating/frying time-points. Fast food restaurant-fried potato chip serving (FFRPCS) aldehyde contents were also monitored. Substantially lower levels of aldehydes were generated in the MRAFO product than those observed in PUFA-richer oils during LSSFEs. Toxicologically-significant concentrations of aldehydes were detected in FFRPCSs, and potato chips exposed to DBRDFEs when using a PUFA-laden sunflower oil frying medium: these contents increased with augmented deep-frying episode repetition. FFRPCS aldehyde contents were 10–25 ppm for each class monitored. In conclusion, the MRAFO product generated markedly lower levels of food-penetrative, toxic aldehydes than PUFA-rich ones during LSSFEs. Since FFRPCS and DBRDFE potato chip aldehydes are predominantly frying oil-derived, PUFA-deplete MRAFOs potentially offer health-friendly advantages.
Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy
Authors: Akinrinade Oyediran , Heliö Tiina , Lekanne Deprez Ronald H. , Jongbloed Jan D. H. , Boven Ludolf G. , van den Berg Maarten P. , Pinto Yigal M. , Alastalo Tero-Pekka , Myllykangas Samuel , Spaendonck-Zwarts Karin van , van Tintelen J. Peter , van der Zwaag Paul A. , Koskenvuo Juha 
Published: March 2019

AbstractRecent advancements in next generation sequencing (NGS) technology have led to the identification of the giant sarcomere gene, titin (TTN), as a major human disease gene. Truncating variants of TTN (TTNtv) especially in the A-band region account for 20% of dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation of TTNtv in human disease; however, missense and non-frameshifting insertions/deletions (NFS-INDELs) are difficult to assess and interpret in clinical diagnostic workflow. Targeted sequencing covering all exons of TTN was performed on a cohort of 530 primary DCM patients from three cardiogenetic centres across Europe. Using stringent bioinformatic filtering, twenty-nine and two rare TTN missense and NFS-INDELs variants predicted deleterious were identified in 6.98% and 0.38% of DCM patients, respectively. However, when compared with those identified in the largest available reference population database, no significant enrichment of such variants was identified in DCM patients. Moreover, DCM patients and reference individuals had comparable frequencies of splice-region missense variants with predicted splicing alteration. DCM patients and reference populations had comparable frequencies of rare predicted deleterious TTN missense variants including splice-region missense variants suggesting that these variants are not independently causative for DCM. Hence, these variants should be classified as likely benign in the clinical diagnostic workflow, although a modifier effect cannot be excluded at this stage.
The metabolic fingerprints of HCV and HBV infections studied by Nuclear Magnetic Resonance Spectroscopy
Authors: Meoni Gaia , Lorini Serena , Monti Monica , Madia Francesco , Corti Giampaolo , Luchinat Claudio , Zignego Anna Linda , Tenori Leonardo , Gragnani Laura 
Published: March 2019

AbstractFew studies are available on metabolic changes in liver injuries and this is the first metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using1H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors. The investigation clearly shows differences in the metabolomic profile of HCV patients before and after effective DAA treatment. Significant changes in metabolites levels in patients undergoing therapy suggest alterations in several metabolic pathways. It has been shown that1H-NMR fingerprinting approach is an optimal technique in predicting the specific infection and the healthy status of studied subjects (Monte-Carlo cross validated accuracies: 86% in the HCV vs HBV model, 98.7% in the HCV vs HC model). Metabolite data collected support the hypothesis that the HCV virus induces glycolysis over oxidative phosphorylation in a similar manner to the Warburg effect in cancer, moreover our results have demonstrated a different action of the two viruses on cellular metabolism, corroborating the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection. This metabolomic study has revealed some alteration in metabolites for the first time (2-oxoglutarate and 3-hydroxybutrate) concerning the HCV-infection model that could explain several extrahepatic manifestations associated with such an infection.
Glycosylated nanostructures in sublingual immunotherapy induce long-lasting tolerance in LTP allergy mouse model
Authors: Rodriguez Maria J. , Ramos-Soriano Javier , Perkins James R. , Mascaraque Ainhoa , Torres Maria J. , Gomez Francisca , Diaz-Perales Araceli , Rojo Javier , Mayorga Cristobalina 
Published: March 2019

AbstractAn effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs). We propose a novel sublingual immunotherapy for peach allergy, using systems, that combine Prup3-T-cell peptides with mannose dendrons (D1ManPrup3 and D4ManPrup3). Peach anaphylactic mice were treated 1, 2 and 5 nM concentrations. Tolerance was assessed one/five weeks after finishing treatment by determining in vivo/in vitro parameters after challenge with Prup3. Only mice receiving D1ManPrup3 at 2 nM were protected from anaphylaxis (no temperature changes, decrease in Prup3-sIgE and -sIgG1 antibody levels, and secreting cells) compared to PBS-treated mice. Moreover, an increase of Treg-cells and regulatory cytokines (IL-10+/IFN-γ+) in CD4+-T-cells and DCs were found. These changes were maintained at least five weeks after stopping treatment. D1ManPrup3 is an effective new approach of immunotherapy inducing protection from anaphylaxis which persists after finishing treatment.
Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington’s disease subjects
Authors: Herman Stephanie , Niemelä Valter , Emami Khoonsari Payam , Sundblom Jimmy , Burman Joachim , Landtblom Anne-Marie , Spjuth Ola , Nyholm Dag , Kultima Kim 
Published: March 2019

AbstractHuntington’s disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.
Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia
Authors: Vishweswaraiah Sangeetha , Swierkowska Joanna , Ratnamala Uppala , Mishra Nitish K. , Guda Chittibabu , Chettiar Shiva S. , Johar Kaid R. , Mrugacz Malgorzata , Karolak Justyna A. , Gajecka Marzena , Radhakrishna Uppala 
Published: March 2019

AbstractMyopia, commonly referred to as nearsightedness, is one of the most common causes of visual disability throughout the world. It affects more people worldwide than any other chronic visual impairment condition. Although the prevalence varies among various ethnic groups, the incidence of myopia is increasing in all populations across globe. Thus, it is considered a pressing public health problem. Both genetics and environment play a role in development of myopia. To elucidate the epigenetic mechanism(s) underlying the pathophysiology of high-myopia, we conducted methylation profiling in 18 cases and 18 matched controls (aged 4–12 years), using Illumina MethylationEPIC BeadChips array. The degree of myopia was variable among subjects, ranging from −6 to −15D. We identified 1541 hypermethylated CpGs, representing 1745 genes (2.0-fold or higher) (false discovery rate (FDR) p ≤ 0.05), multiple CpGs were p < 5 × 10−8 with a receiver operating characteristic area under the curve (ROC-AUC) ≥ 0.75 in high-myopia subjects compared to controls. Among these, 48 CpGs had excellent correlation (AUC ≥ 0.90). Herein, we present the first genome-wide DNA methylation analysis in a unique high-myopia cohort, showing extensive and discrete methylation changes relative to controls. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination.
Altering brain dynamics with transcranial random noise stimulation
Authors: van der Groen Onno , Mattingley Jason B. , Wenderoth Nicole 
Published: March 2019

AbstractRandom noise can enhance the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. Here we used a computational model to predict the effect of noise on perceptual dominance durations. Subsequently we compared the model prediction to a series of experiments where we measured binocular rivalry dynamics when noise (zero-mean Gaussian random noise) was added either to the visual stimulus (Exp. 1) or directly to the visual cortex (Exp. 2) by applying transcranial Random Noise Stimulation (tRNS 1 mA, 100–640 Hz zero -mean Gaussian random noise). We found that adding noise significantly reduced the mixed percept duration (Exp. 1 and Exp. 2). Our results are the first to demonstrate that both central and peripheral noise can influence state-switching dynamics of binocular rivalry under specific conditions (e.g. low visual contrast stimuli), in line with a SR-mechanism.
Quantitative evaluation of ontology design patterns for combining pathology and anatomy ontologies
Authors: Alghamdi Sarah M. , Sundberg Beth A. , Sundberg John P. , Schofield Paul N. , Hoehndorf Robert 
Published: March 2019

AbstractData are increasingly annotated with multiple ontologies to capture rich information about the features of the subject under investigation. Analysis may be performed over each ontology separately, but recently there has been a move to combine multiple ontologies to provide more powerful analytical possibilities. However, it is often not clear how to combine ontologies or how to assess or evaluate the potential design patterns available. Here we use a large and well-characterized dataset of anatomic pathology descriptions from a major study of aging mice. We show how different design patterns based on the MPATH and MA ontologies provide orthogonal axes of analysis, and perform differently in over-representation and semantic similarity applications. We discuss how such a data-driven approach might be used generally to generate and evaluate ontology design patterns.
Capsaicin Protects Against Cisplatin Ototoxicity by Changing the STAT3/STAT1 Ratio and Activating Cannabinoid (CB2) Receptors in the Cochlea
Authors: Bhatta Puspanjali , Dhukhwa Asmita , Sheehan Kelly , Al Aameri Raheem F.H , Borse Vikrant , Ghosh Sumana , Sheth Sandeep , Mamillapalli Chaitanya , Rybak Leonard , Ramkumar Vickram , Mukherjea Debashree 
Published: March 2019

AbstractCapsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and causes rapid desensitization. Capsaicin also ameliorates cisplatin-induced nephrotoxicity. Cisplatin, a commonly used anti-neoplastic agent for solid tumors causes significant hearing loss, nephrotoxicity and peripheral neuropathy. Upregulation of cochlear TRPV1 expression is related to cisplatin-mediated ototoxicity. Here we report that direct TRPV1 activation by localized trans-tympanic (TT) or oral administration of capsaicin (TRPV1 agonist) prevents cisplatin ototoxicity by sustained increased activation of pro-survival transcription factor signal transducer and activator of transcription (STAT3) in the Wistar rat. Cisplatin treatment produced prolonged activation of pro-apoptotic Ser727 p-STAT1 and suppressed Tyr705-p-STAT3 for up to 72 h in the rat cochlea. Our data indicate that capsaicin causes a transient STAT1 activation via TRPV1 activation, responsible for the previously reported temporary threshold shift. Additionally, we found that capsaicin increased cannabinoid receptor (CB2) in the cochlea, which leads to pro-survival Tyr705-p-STAT3 activation. This tilts the delicate balance of p-STAT3/p-STAT1 towards survival. Furthermore, capsaicin mediated protection is lost when CB2 antagonist AM630 is administered prior to capsaicin treatment. In conclusion, capsaicin otoprotection appears to be mediated by activation of CB2 receptors in the cochlea which are coupled to both STAT1 and STAT3 activation.
Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
Authors: Sukowati Caecilia H. C. , Anfuso Beatrice , Fiore Esteban , Ie Susan I. , Raseni Alan , Vascotto Fulvia , Avellini Claudio , Mazzolini Guillermo , Tiribelli Claudio 
Published: March 2019

AbstractHyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.
The kinetics of folding of the NSH2 domain from p85
Authors: Visconti Lorenzo , Malagrinò Francesca , Toto Angelo , Gianni Stefano 
Published: March 2019

AbstractSH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics. Taking advantage of double mixing stopped flow experiments and site directed mutagenesis we demonstrate that such behavior is due to the cis/trans isomerization of the peptide bond between D73 and P74, being in a cis conformation in the native protein. Our data are discussed in comparison with previous works on the folding of other SH2 domains.
Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture
Authors: Baldan Jonathan , Houbracken Isabelle , Rooman Ilse , Bouwens Luc 
Published: March 2019

AbstractHuman pancreatic exocrine cells were cultured in 3D suspension and formed pancreatospheres composed of acinar-derived and duct-like cells. We investigated, up to 6 days, the fate of human pancreatic acinar cells using fluorescein-conjugated Ulex Europaeus Agglutinin 1 lectin, a previously published acinar-specific non-genetic lineage tracing strategy. At day 4, fluorescence-activated cell sort for the intracellularly incorporated FITC-conjugated UEA1 lectin and the duct-specific CA19.9 surface marker, distinguished acinar-derived cells (UEA1+CA19.9−) from duct-like cells (UEA1−CA19.9+) and acinar-to-duct-like transdifferentiated cells (UEA1+CA19.9+). mRNA expression analysis of the acinar-derived (UEA1+CA19.9−) and duct-like (UEA1-CA19.9+) cell fractions with concomitant immunocytochemical analysis of the pancreatospheres revealed acquisition of an embryonic signature in the UEA1+CA19.9− acinar-derived cells characterized by de novo expression of SOX9 and CD142, robust expression of PDX1 and surface expression of GP2. The colocalisation of CD142, a multipotent pancreatic progenitor surface marker, PDX1, SOX9 and GP2 is reminiscent of a cellular state present during human embryonic development. Addition of TGF-beta signalling inhibitor Alk5iII, induced a 28-fold increased KI67-labeling in pancreatospheres, more pronounced in the CD142+GP2+ acinar-derived cells. These findings with human cells underscore the remarkable plasticity of pancreatic exocrine acinar cells, previously described in rodents, and could find applications in the field of regenerative medicine.