bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic lung, an underrated complication from restrictive functional pattern to pulmonary hypertension
Authors: Fuso Leonello , Pitocco Dario , Antonelli‐Incalzi Raffaele 
Published: March 2019

AbstractIn patients with type 1 and type 2 diabetes mellitus (DM), respiratory function abnormalities have been reported with regard to lung volumes, pulmonary diffusing capacity, control of ventilation, bronchomotor tone, and neuroadrenergic bronchial innervation. Indeed, the decrease in lung volumes and the impairment of diffusing capacity might have important clinical implications. Furthermore, there is an increasing evidence of a link between DM and pulmonary hypertension (PH) related to an involvement of the pulmonary vascular structures. These findings support the view of the lung as target organ in DM. In this paper, we briefly describe the main derangements of the respiratory system in DM and the inherent mechanisms.
A strong colonizer rules the trematode guild in an intertidal snail host
Authors: Alda Pilar , Bonel Nicolás , Cazzaniga Néstor J. , Martorelli Sergio R. , Lafferty Kevin D. 
Published: March 2019

AbstractWe examined the extent to which supply‐side, niche, and competition theories and concepts help explain a trematode community in which one species comprises 87% of the trematode individuals, and the remaining 15 species each have <3%. We collected and dissected the common and wide‐ranging snail host Heleobia australis over four seasons from three distinct habitats from the intertidal area of the Bahía Blanca estuary, Argentina. Inside a snail, trematodes interact with each other with outcomes that depend on facilitation, competition, and preemption, suggesting that dominant species should be common. The abundant trematode species, Microphallus simillimus, is a weak competitor, but has life‐history traits and strategies associated with higher colonization ability that could increase its probability of invading the host first, allowing it to preempt the rare species. Rather than segregate by habitat, trematode species aggregated in pans during the summer where dominant trematode species often excluded subordinate ones. Despite losses to competition, and a lack of niche partitioning, M. simillimus ruled this species‐rich trematode guild through strong recruitment and (potentially) preemption. Therefore, extremely skewed species abundance distributions, like this one, can derive from extremely skewed colonization abilities.
A 17‐Beta‐Hydroxysteroid Dehydrogenase 13 Variant Protects From Hepatocellular Carcinoma Development in Alcoholic Liver Disease
Authors: Yang Jie , Trépo Eric , Nahon Pierre , Cao Qian , Moreno Christophe , Letouzé Eric , Imbeaud Sandrine , Bayard Quentin , Gustot Thierry , Deviere Jacques , Bioulac‐Sage Paulette , Calderaro Julien , Ganne‐Carrié Nathalie , Laurent Alexis , Blanc Jean Frédéric , Guyot Erwan , Sutton Angela , Ziol Marianne , Zucman‐Rossi Jessica , Nault Jean‐Charles 
Published: March 2019

Recently, a loss of function variant (rs72613567) in 17‐beta‐hydroxysteroid dehydrogenase 13 (HSD17B13) has been identified as protective of nonalcoholic (NAFLD) and alcoholic liver disease (ALD). However, the role of this single‐nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) is currently unknown. A total of 3,315 European patients with HCC (n = 1,109) or without HCC, but with chronic liver disease (CLD; n = 2,206), from four centers were analyzed either by whole‐exome sequencing (WES; exploratory cohort, 285 HCC) or genotyped for HSD17B13 rs72613567 (validation cohort, 824 HCC and all CLD). We included a control group of 33,337 healthy European individuals from the Exome Aggregation Consortium. We compared distribution of genotype using the chi‐square test and logistic regression. In the exploratory cohort analyzed by WES, frequency of the TA allele of HSD17B13 rs72613567 was significantly decreased in HCC patients compared to healthy controls (P = 1.52 × 10−06). In the validation cohort, frequency of TA allele carriers was also decreased in patients with CLD and without HCC (39%) compared to healthy individuals (47%; P < 0.0001). The protective effect of the TA allele of HSD17B13 rs72613567 was identified in patients with ALD (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.65‐0.82; P < 0.0001), NAFLD (OR = 0.64; 95% CI, 0.49‐0.83; P = 0.0007), and hepatitis C (OR = 0.71; 95% CI, 0.60‐0.85; P = 0.0002). In patients with ALD, the proportion of TA allele carriers with HCC was significantly lower (32%) than in CLD patients without HCC (40%), even after adjustment for age, sex, and fibrosis (OR = 0.64; 95% CI, 0.46‐0.87; P = 0.005). Conclusion: The HSD17B13 rs72613567 loss of function variant is protective of HCC development in patients with ALD.
Patients With Acute on Chronic Liver Failure Grade 3 Have Greater 14‐Day Waitlist Mortality Than Status‐1a Patients
Authors: Sundaram Vinay , Shah Parth , Wong Robert J. , Karvellas Constantine J. , Fortune Brett E. , Mahmud Nadim , Kuo Alexander , Jalan Rajiv 
Published: March 2019

Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF‐3) portends low survival without transplantation, which may not be reflected by the Model for End‐Stage Liver Disease‐Sodium (MELD‐Na) score. We compared short‐term waitlist mortality for patients listed status 1a and those with ACLF‐3 at listing. Data were analyzed from the United Network for Organ Sharing database, years 2002‐2014, for 3,377 patients listed status 1a and 5,099 patients with ACLF‐3. Candidates with ACLF were identified based on the European Association for the Study of the Liver Chronic Liver Failure Consortium criteria. MELD‐Na score was treated as a categorical variable of scores <36, 36‐40, and >40. We used competing risks regression to assess waitlist mortality risk. Evaluation of outcomes through 21 days after listing demonstrated a rising trend in mortality among ACLF‐3 patients at 7 days (18.0%), 14 days (27.7%), and 21 days (32.7%) (P < 0.001) compared to a stable trend in mortality among individuals listed as status 1a at 7 days (17.9%), 14 days (19.3%), and 21 days (19.8%) (P = 0.709). Multivariable modeling with adjustment for MELD‐Na category revealed that patients with ACLF‐3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31‐1.61) within 14 days of listing compared to status‐1a candidates. Analysis of the interaction between MELD‐Na category and ACLF‐3 showed that patients with ACLF‐3 had greater risk of 14‐day mortality than status‐1a‐listed patients, across all three MELD‐Na categories. Conclusion: Patients with ACLF‐3 at the time of listing have greater 14‐day mortality than those listed as status 1a, independent of MELD‐Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF‐3.
Association Between Institutional Factors and Long‐Term Survival Following Transjugular Intrahepatic Portosystemic Shunt
Authors: Mah Jeffrey M. , DeWit Yvonne , Djerboua Maya , Menard Alexandre , Booth Christopher M. , Flemming Jennifer A. 
Published: March 2019

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure designed to treat portal hypertension. Hospital teaching status is an institutional factor found to be predictive of outcomes following several complex procedures; however, its impact on outcomes following TIPS is unknown. The aim of this study was to determine the association between hospital teaching status and long‐term survival in patients with cirrhosis receiving TIPS. We performed a retrospective population‐based cohort study using linked administrative health data from Ontario, Canada. Adult patients with cirrhosis who received TIPS between January 1, 1998, and December 31, 2016, with follow‐up until December 31, 2017, were included. Hospital teaching status was defined based on hospital participation in the instruction of medical students and/or resident physicians. Liver transplant‐free (LTF) survival was evaluated using Kaplan‐Meier analysis, and overall survival was assessed using competing risks regression analysis, which accounted for hospital clustering. A total of 857 unique patients were included (mean age 57.1 years; 69.1% male). The TIPS procedures were performed in teaching hospitals (84.3%) as well as nonteaching hospitals (15.7%). Median LTF survival was more than twice as long for procedures performed in teaching hospitals compared to nonteaching hospitals (2.2 years versus 0.9 year, respectively; P < 0.001). After adjusting for confounders and clustering, hospital teaching status was not independently associated with mortality (nonteaching subdistribution hazard ratio [sHR], 1.32; 95% confidence interval [CI], 0.97‐1.81; P = 0.08); however, annual hospital procedure volume was (per unit increase sHR, 0.96; 95% CI, 0.93‐0.99; P = 0.003). Conclusion: Hospital procedure volume is associated with long‐term survival following TIPS. These results further support the centralization of TIPS to high‐volume hospitals to improve long‐term outcomes in this population.
The Fish Community Index: A Practical Management Tool for Monitoring and Reporting Estuarine Ecological Condition
Authors: Hallett Chris S , Trayler Kerry M , Valesini Fiona J 
Published: March 2019

Abstract
Indicators of ecological health based on biological communities, including numerous multimetric indices, are used worldwide to assess and report the condition of aquatic ecosystems such as estuaries. Yet, these tools have rarely been applied to support estuary management in Australia. We present a case study of one such multimetric indicator, the Fish Community Index (FCI), which was developed and applied to quantify the ecological condition of estuaries in southwestern Australia (SWA). We outline the rationale, development, and implementation of the FCI for annual monitoring and reporting of the ecological condition of a highly urbanized estuary, highlighting the key research and management outcomes that it has delivered, and evaluating its potential future applications to support estuary management more broadly, both across Australia and internationally. The FCI is founded upon a conceptually simple and scientifically robust rationale and is sensitive to the ecological stressors that affect many estuaries across the region (e.g., hypoxia, algal blooms). Together with an accompanying annual fish monitoring regime, the FCI provides managers with a consistent, robust basis for quantifying and reporting spatiotemporal changes in estuary condition, with easily comprehensible outputs that facilitate communication with stakeholders, ranging from politicians to the general public. We attribute the successful implementation of this management tool to several characteristics, namely 1) support from a long-term, collaborative partnership between managers and researchers; 2) comprehensive testing and validation of the index prior to implementation; 3) a robust, standardized monitoring regime; and 4) sustained resourcing from managers to implement the index as part of a reporting framework. The FCI has also been applied to other SWA estuaries and could provide a platform for more coordinated assessment and reporting of estuarine condition at the bioregional scale, thereby helping to improve the gap in reporting on the biotic integrity of Australian estuaries. Integr Environ Assess Manag 2019;15:726–738. © 2019 SETAC.
When Are Adverse Outcome Pathways and Associated Assays “Fit for Purpose” for Regulatory Decision-Making and Management of Chemicals?
Authors: Coady Katie , Browne Patience , Embry Michelle , Hill Thomas , Leinala Eeva , Steeger Thomas , Maślankiewicz Lidka , Hutchinson Tom 
Published: March 2019

Abstract
There have been increasing demands for chemical hazard and risk assessments in recent years. Chemical companies have expanded internal product stewardship initiatives, and jurisdictions have increased the regulatory requirements for the manufacture and sale of chemicals. There has also been a shift in chemical toxicity evaluations within the same time frame, with new methodologies being developed to improve chemical safety assessments for both human health and the environment. With increased needs for chemical assessments coupled with more diverse data streams from new technologies, regulators and others tasked with chemical management activities are faced with increasing workloads and more diverse types of data to consider. The Adverse Outcome Pathway (AOP) framework can be applied in different scenarios to integrate data and guide chemical assessment and management activities. In this paper, scenarios of how AOPs can be used to guide chemical management decisions during research and development, chemical registration, and subsequent regulatory activities such as prioritization and risk assessment are considered. Furthermore, specific criteria (e.g., the type and level of AOP complexity, confidence in the AOP, as well as external review and assay validation) are proposed to examine whether AOPs and associated tools are fit for purpose when applied in different contexts. Certain toxicity pathways are recommended as priority areas for AOP research and development, and the continued use of AOPs and defined approaches in regulatory activities are recommended. Furthermore, a call for increased outreach, education, and enhanced use of AOP databases is proposed to increase their utility in chemicals management. Integr Environ Assess Manag 2019;15:633–647. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Nimotuzumab inhibits epithelial–mesenchymal transition in prostate cancer by targeting the Akt/YB‐1/AR axis
Authors: Hu Sheng , Duan Yi‐Xing , Zhou Qiang , Wang Yong , Lu Qiang 
Published: March 2019

ABSTRACTNimotuzumab is a humanized anti‐EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3‐AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial–mesenchymal transition (EMT) in vitro and in vivo. The EMT makers were detected by immunohistochemistry, qRT‐PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y‐box binding protein‐1 (YB‐1)/AR axis in nimotuzumab‐induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB‐1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo, which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell‐cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3‐AR cells in vitro. On the molecular level, nimotuzumab inactivated Akt and YB‐1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3‐AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB‐1 activation, and both critical for regulating the levels of AR and EMT‐related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB‐1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1–14, 2019
Undercarboxylated Osteocalcin Improves Insulin-Stimulated Glucose Uptake in Muscles of Corticosterone-Treated Mice
Authors: Lin Xuzhu , Parker Lewan , McLennan Emma , Hayes Alan , McConell Glenn , Brennan-Speranza Tara C , Levinger Itamar 
Published: March 2019

ABSTRACT
Short-term administration of glucocorticoids (GCs) impairs muscle insulin sensitivity at least in part via the reduction of undercarboxylated osteocalcin (ucOC). However, whether ucOC treatment reverses the GC-induced muscle insulin resistance remains unclear. To test the hypothesis that ucOC directly ameliorates impaired insulin-stimulated glucose uptake (ISGU) induced by short-term GC administration in mice muscle and to identify the molecular mechanisms, mice were implanted with placebo or corticosterone (CS) slow-release pellets. Two days post-surgery, insulin-tolerance tests (ITTs) were performed. On day 3, serum was collected and extensor digitorum longus (EDL) and soleus muscles were isolated and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 µU/mL), or both. Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins were assessed. CS administration reduced both serum osteocalcin and ucOC levels, whole-body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment restored ISGU in CS-affected muscle, without increasing non-insulin-stimulated glucose uptake. In CS-affected EDL muscle, ucOC enhanced insulin action on phosphorylated (p-)protein kinase B (Akt)Ser473and the p-extracellular signal-regulated kinase isoform 2 (ERK2)Thr202/Tyr204/total (t)ERK2 ratio, which correlated with ISGU. In CS-affected soleus muscle, ucOC enhanced insulin action on p-mammalian target of rapamycin (mTOR)Ser2481, the p-mTORSer2481/tmTOR ratio, p-Akt substrate of 160kD (AS160)Thr642, and p-protein kinase C (PKC) (pan)Thr410, which correlated with ISGU. Furthermore, p-PKC (pan)Thr410 correlated with p-AktSer473 and p-AS160Thr642. ucOC exerts direct insulin-sensitizing effects on CS-affected mouse muscle, likely through an enhancement in activity of key proteins involved in both insulin and ucOC signaling pathways. Furthermore, these effects are muscle type-dependent. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Circular RNA expression profile in human fibroblast premature senescence after repeated ultraviolet B irradiations revealed by microarray
Authors: Si Chenchen , Wang Jie , Ma Weiwei , Hua Hui , Zhang Meijie , Qian Wen , Zhou Bingrong , Luo Dan 
Published: March 2019

AbstractCircular RNA (circRNA) is a class of noncoding RNA that regulates the activity of microRNAs and gene expression. Altered circRNA expression is associated with human diseases. The present study profiled differentially expressed circRNAs in the ultraviolet B stress‐induced human fibroblast premature senescence (UVB‐SIPS) model, and assessed the role of circRNA_100797 in UVB‐SIPS. The UVB‐SIPS model was confirmed by ß‐galactosidase staining, cell viability CCK‐8 assay, and flow cytometric cell cycle distribution assay, and subjected to circRNA gene chip profiling. These differentially expressed circRNAs were analyzed using the clusterProfiler R package for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways. The selected circRNAs were confirmed using quantitative reverse transcription polymerase chain reaction (qRT‐PCR), the relationship of circRNA_100797 with miR‐23a‐5p was assessed using luciferase reporter assay, and their functions were determined by qRT‐PCR and western blot analysis. A total of 472 differentially expressed circRNAs occurred in the UVB‐SIPS. qRT‐PCR confirmed five of eight differentially expressed circRNAs. The GO and KEGG analyses revealed that these differently expressed circRNAs function in biology process, cell component, and molecular function. Furthermore, it was found that circRNA_100797 had a low expression in UVB‐SIPS. However, when circRNA_100797 was overexpressed, the acceleration of cell proliferation and alleviation of cell cycle arrest were observed. Moreover, circRNA_100797 could target miR‐23a‐5p, their expression levels were inversely associated in fibroblasts, and the miR‐23a‐5p overexpression blocked the effect of the overexpression of circRNA_100797 in UVB‐SIPS. The present study demonstrated that circRNA_100797 acts as a sponge of miR‐23a‐5p, and has a photoprotection role in UVB‐irradiated fibroblasts.
Inhibition of lncRNA HULC improves hepatic fibrosis and hepatocyte apoptosis by inhibiting the MAPK signaling pathway in rats with nonalcoholic fatty liver disease
Authors: Shen Xingtong , Guo Huaiyuan , Xu Jinjin , Wang Jinliang 
Published: March 2019

AbstractThis study is conducted to investigate the role of long noncoding RNA highly upregulated in liver cancer (lncRNA HULC) on hepatic fibrosis and hepatocyte apoptosis by inhibiting the mitogen‐activated protein kinase (MAPK) signaling pathway in rats with nonalcoholic fatty liver disease (NAFLD). The successfully modeled rats were injected with HULC siRNA or small interfering RNA (siRNA) negative control into the tail vein. The expression of HULC in liver tissues was detected by reverse transcription quantitative polymerase reaction chain. The role of HULC in pathological state and liver function‐related indexes of liver lipid deposition, the degree of hepatic fibrosis and hepatocyte apoptosis in rats with NAFLD were also investigated through a series of experiments. Increased expression of HULC was found in liver tissue of NAFLD rats. Inhibition of HULC improved the pathological state and liver function‐related indexes of liver lipid deposition, improved the degree of hepatic fibrosis, reduced hepatocyte apoptosis, and inhibited the MAPK signaling pathway in the liver tissue of NAFLD rats. The inhibition of p38 and JNK improved the pathological state of liver lipid deposition and liver function to some extent, improved the degree of hepatic fibrosis, and reduced the apoptosis of hepatocytes in NAFLD rats. Collectively, this present study provides evidence that inhibition of lncRNA HULC improves hepatic fibrosis and decrease hepatocyte apoptosis in rats with NAFLD by inhibiting the MAPK signaling pathway.
Epithelial–mesenchymal transition induced cancer‐stem‐cell‐like characteristics in hepatocellular carcinoma
Authors: Jing Li , Ruan Zhiping , Sun Haifeng , Li Qing , Han Lili , Huang Lanxuan , Yu Sizhe , Wang Yu , Guo Hui , Jiao Min 
Published: March 2019

AbstractHepatocellular carcinoma in China accounts for half of the world's incidence. Both epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are thought to be involved in tumor malignant progression. However, the relationship between EMT and CSCs is still unclear. Bioinformatics analysis was performed to evaluate the relationship between EMT and CSCs. The EMT and CSC regulatory mechanism was investigated through Transwell, wound‐healing, sphere formation, colony‐forming, and western blotting assays. Immunofluorescence and immunoprecipitation were used to study the interaction of hypoxia inducible factor 1α (HIF‐1α) /Notch1. Immunohistochemical study was applied to investigate the expression pattern in the process of hepatocellular carcinogenesis and development. In our present study, bioinformatics results indicate that the expression of EMT‐related molecules is correlated with CSCs. In vitro studies indicated that EMT activation could induce CSC characteristics. Notch1 was confirmed to mediate the process of EMT‐induced CSCs through the interaction with HIF‐1α directly. Our findings indicate that EMT could induce CSC‐like characteristics, which is mediated by HIF‐1α‐upregulated Notch intracellular domain expression.