bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis
Authors: Dai Da-nian , Li Yan , Chen Bo , Du Yong , Li Shi-bing , Lu Shi-xun , Zhao Zhi-ping , Zhou Ai-jun , Xue Ning , Xia Tian-liang , Zeng Mu-sheng , Zhong Qian , Wei Wei-dong 
Published: May 2017

Abstract
Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer.

Key messages

High CST1 expression is negatively correlated with survival of breast cancer patients.

CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells.

CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer.
Extracellular low‐n oligomers of tau cause selective synaptotoxicity without affecting cell viability
Authors: Kaniyappan Senthilvelrajan , Chandupatla Ram Reddy , Mandelkow Eva‐Maria , Mandelkow Eckhard 
Published: May 2017

AbstractIntroductionTau‐mediated toxicity in Alzheimer's disease is thought to operate through low‐n oligomers, rather than filamentous aggregates. However, the nature of oligomers and pathways of toxicity are poorly understood. Therefore, we investigated structural and functional aspects of highly purified oligomers of a pro‐aggregant tau species.MethodsPurified oligomers of the tau repeat domain were characterized by biophysical and structural methods. Functional aspects were investigated by cellular assays ((3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay of cell viability, lactate dehydrogenase release assay [for cell toxicity], reactive oxygen species production, and calcium assay), combined with analysis of neuronal dendritic spines exposed to oligomers.ResultsPurified low‐n oligomers are roughly globular, with sizes around 1.6 to 5.4 nm, exhibit an altered conformation, but do not have substantial β‐structure. Treatment of primary neurons with oligomers impairs spine morphology and density, accompanied by increased reactive oxygen species and intracellular calcium, but without affecting cell viability (by (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay of cell viability and lactate dehydrogenase release assay [for cell toxicity]).DiscussionTau oligomers are toxic to synapses but not lethal to cells.
Electronic Health Record Transition Considerations
Authors: Penrod Louis E. 
Published: May 2017

AbstractAfter an initial phase of electronic health record (EHR) solutions for both independent practices and larger health care organizations, we are now entering a period in which transitioning between EHRs is becoming more common. Many of the decisions and implementation processes for an EHR transition are similar to those encountered during the transition from paper records to an EHR. Detailed project planning and management are essential to keep the effort on track and within budget to a successful conclusion. One major difference between the 2 situations is the possibility of migrating patient data by using automation. Understanding the implications of structured and unstructured data to manage the data migration between EHR systems is important to ensure success of the effort. Access to legacy data after the transition for both patient care and release of information to external parties is also critical to understand and manage proactively.
Negotiating Positive Non-interventionism: Regulating Hong Kong's Finance Companies, 1976–1986
Authors: Schenk Catherine R. 
Published: May 2017

AbstractSince colonial times to the present day, Hong Kong's position as a global financial centre is one of the enduring economic strengths of the territory. This success is often attributed to the distinctive role of the state, coined in the 1970s by the-then financial secretary, Sir Philip Haddon-Cave, as “positive non-interventionism.” The relationship between the market and the state has also been characterized as a form of corporatism, particularly in the financial sector as bankers were able to influence policy. However, closer examination of the behind-the-scenes relations between bankers and the state reveals a much more complex relationship, with the banks seeking protection that the government was not willing to provide. Moreover, the reluctance to regulate financial markets resulted in piecemeal interventions and weak implementation that undermined the stability of this sector and of the economy as a whole. This paper demonstrates the confusion over the concept and practicalities of positive non-interventionism, even for Haddon-Cave, and how the concept evolved towards a policy of “when in doubt, do nothing” during a period of financial instability. Along the way, the paper presents new evidence about the origins of Hong Kong's current banking structure.
Key drivers of patient experience in ambulatory paediatric cardiology
Authors: Allam Shalini D. , Mehta Mary , Ben Khallouq Bertha , Burrows James F. , Rosen Paul 
Published: May 2017

AbstractPatient experience is becoming a central focus of healthcare. A broad range of studies on how to increase patient satisfaction ratings exists; however, they lack the specificity to adequately guide physicians and hospitals on how to improve patient experience. The objective of this study was to define the aspects of patient experience within paediatric cardiologist practices that can serve as predictors of excellent patient satisfaction. From 1 January, 2013 to 28 February, 2015 (26 months), outpatients who visited paediatric cardiologists were asked to complete a 39-question patient satisfaction survey regarding their experience. Surveys were collected over a 26-month period by Press Ganey, an independent provider of patient satisfaction surveys. Participants were asked to rate their experience on a 1–5 Likert-scale: a score of 1 demonstrated a “poor” experience, whereas a score of 5 demonstrated a “very good” experience. This retrospective study of 2468 responses determined that cheerfulness of the practice (r=0.85, p<0.001), a cohesive staff (r=0.83, p<0.001), and a care provider explaining problems and conditions (r=0.81, p<0.001) were key aspects of a paediatric cardiologist’s practice that can be used as predictors of overall patient satisfaction. Awareness of how doctors can personalise a patient’s experience is vital to achieve greater patient satisfaction and, ultimately, better patient outcomes.
Cross-cultural adaptation and validation of the Newest Vital Sign (NVS) health literacy instrument in general population and highly educated samples of Brazilian adults
Authors: Rodrigues Renne , de Andrade Selma Maffei , González Alberto Durán , Birolim Marcela Maria , Mesas Arthur Eumann 
Published: May 2017

AbstractObjectiveThe present work aimed at cross-cultural adaptation and validation of the health literacy assessment tool Newest Vital Sign (NVS) in general population (GP) and highly educated (HE) samples of Brazilian adults.DesignAn expert committee reviewed the translation and back-translation processes and the cultural adaptation. The construct validity was analysed with confirmatory factor analysis and via associations with features of the study population.SettingThe final validation test was performed in two different populations from Londrina, a large town in southern Brazil.SubjectsBrazilian adults: GP (adult clients of community pharmacies;n189) and HE (public school teachers;n301).ResultsThe tool under validation showed good cross-cultural adaptation and internal consistency, with Cronbach’sαof 0·75 for GP and 0·74 for HE. Confirmatory factor analysis showed acceptable models and identified two independent factors according to the relationship between components and numeracy for both GP and HE data. According to the Brazilian Portuguese version of the NVS instrument (NVS-BR), 48·7 % of GP and 33·5 % of HE presented adequate health literacy; this condition was inversely associated with age for both populations and directly correlated with educational level for GP.ConclusionsThe NVS-BR showed good validity in two different populations of Brazilian adults and can be considered an alternative in screening for inadequate health literacy.
MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2
Authors: Wang Yang , Du Jinghua , Niu Xuemin , Fu Na , Wang Rongqi , Zhang Yuguo , Zhao Suxian , Sun Dianxing , Nan Yuemin 
Published: May 2017

AbstractNonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine–choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs). A dual-luciferase activity assay confirmed that transforming growth factor-beta receptors (TGFBRs) 1 and 2 were both the target genes of miR-130a-3p. The hepatic expression of TGFBR1 and TGFBR2 was significantly increased. Moreover, the overexpression of miR-130a-3p in HSCs inhibited HSC activation and proliferation, concomitant with the decreased expression of TGFBR1, TGFBR2, Smad2, Smad3, matrix metalloproteinase-2 (MMP-2), MMP-9, type I collagen (Col-1), and Col-4. In addition, the overexpression of miR-130a-3p promoted HSC apoptosis by inducing the expression of caspase-dependent apoptosis genes. Transfection with si-TGFBR1 and si-TGFBR2 revealed effects on HSC function that were consistent with those of miR-130a-3p. TGFBR1 and TGFBR2 rescued the miR-130a-3p-mediated reductions in the mRNA and protein expression levels of Smad2, Smad3, Col-1, and Col-4. In conclusion, our findings suggest that miR-130a-3p might play a critical role in negatively regulating HSC activation and proliferation in the progression of nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-β/SMAD signaling pathway.
MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer
Authors: Li Nana , Miao Yuan , Shan Yujia , Liu Bing , Li Yang , Zhao Lifen , Jia Li 
Published: May 2017

AbstractAccumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve in the tumorigenesis, progression and even lead to poor prognosis of various carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p (miR-93) levels were confirmed to be significantly upregulated in breast cancer clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A). Moreover, further research stated that the capability of migration, invasion and proliferation changed along with the altered expression of miR-106b and miR-93 in breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR-93, which were inversely expressed in PTEN overexpression tissues or cells. Based on the investigation, miR-106b and miR-93 induced the migration, invasion and proliferation and simultaneously enhanced the activity of phosphatidylinositol-3 kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti-miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly targeted by these miRNAs and acted as the potential therapeutic target for breast cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted cell progression through PI3K/Akt pathway in breast cancer.
Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ–p53–p21 signaling pathway
Authors: Jung Seung Hee , Lee Hyung Chul , Hwang Hyun Jung , Park Hyun A , Moon Young-Ah , Kim Bong Cho , Lee Hyeong Min , Kim Kwang Pyo , Kim Yong-Nyun , Lee Byung Lan , Lee Jae Cheol , Ko Young-Gyu , Park Heon Joo , Lee Jae-Seon 
Published: May 2017

AbstractAcyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53–p21 signaling pathway without a DNA damage response. PKCζ was specifically involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of the p53–p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8, 9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive to genotoxic stresses. However, none of those had a role in cytostasis via activation of the PKCζ–p53–p21 signaling pathway. Analysis of the ACOT7 prognostic value revealed that low ACOT7 levels prolonged overall survival periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were higher in lung cancer patient tissues compared to normal tissues. We also observed a synergistic effect of ACOT7 depletion in combination with either IR or doxorubicin on cell proliferation in breast and lung cancer cells. Together, our data suggest that a low level of ACOT7 may be involved, at least in part, in the prevention of human breast and lung cancer development via regulation of cell cycle progression.
Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme
Authors: Wang Lin , Gundelach Justin H , Bram Richard J 
Published: May 2017

AbstractCancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality. We report that NIM811, a small molecule cyclophilin-binding inhibitor, induces catastrophic vacuolization and cell death in GBM cells. These unique features are distinct from many known cell death pathways, and are associated with an incompletely defined cell death mechanism known as paraptosis. We found that NIM811-induced paraptosis is due to unresolved ER stress. The abnormal upregulation of protein translation was responsible for the build-up of misfolded or unfolded proteins in ER, whereas pro-survival autophagy and UPR signals were shutdown during prolonged treatment with NIM811. Although cycloheximide has been claimed to suppress paraptosis, instead we find that it only temporarily delayed vacuole formation, but actually enhanced paraptotic cell death in the long term. On the other hand, mTOR inhibitors rescued cells from NIM811-induced paraptosis by sustaining autophagy and the UPR, while specifically restraining cap-dependent translation. These findings not only provide new insights into the mechanisms underlying paraptosis, but also shed light on a potential approach to enhance GBM treatment.
Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif
Authors: de Opakua Alain Ibáñez , Parag-Sharma Kshitij , DiGiacomo Vincent , Merino Nekane , Leyme Anthony , Marivin Arthur , Villate Maider , Nguyen Lien T. , de la Cruz-Morcillo Miguel Angel , Blanco-Canosa Juan B. , Ramachandran Sekar , Baillie George S. , Cerione Richard A. , Blanco Francisco J. , Garcia-Marcos Mikel 
Published: May 2017

AbstractHeterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation.
The effects of forest canopy shading and turbulence on boundary layer ozone
Authors: Makar P. A. , Staebler R. M. , Akingunola A. , Zhang J. , McLinden C. , Kharol S. K. , Pabla B. , Cheung P. , Zheng Q. 
Published: May 2017

AbstractThe chemistry of the Earth’s atmosphere close to the surface is known to be strongly influenced by vegetation. However, two critical aspects of the forest environment have been neglected in the description of the large-scale influence of forests on air pollution: the reduction of photolysis reaction rates and the modification of vertical transport due to the presence of foliage. Here we show that foliage shading and foliage-modified vertical diffusion have a profound influence on atmospheric chemistry, both at the Earth’s surface and extending throughout the atmospheric boundary layer. The absence of these processes in three-dimensional models may account for 59–72% of the positive bias in North American surface ozone forecasts, and up to 97% of the bias in forested regions within the continent. These processes are shown to have similar or greater influence on surface ozone levels as climate change and current emissions policy scenario simulations.
Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation
Authors: Ji Yapeng , Yang Chuanzhen , Tang Zefang , Yang Yongfeng , Tian Yonglu , Yao Hongwei , Zhu Xi , Zhang Zemin , Ji Jiafu , Zheng Xiaofeng 
Published: May 2017

AbstractTargeting the specific metabolic phenotypes of colorectal cancer stem cells (CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC) patients with poor prognosis and relapse. However, the context-dependent metabolic traits of CRCSCs remain poorly elucidated. Here we report that adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal domain of LDHA, the key regulator of glycolysis, and depends on its adenylate kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the hyperactive Warburg effect and the lower cellular ROS level and conferring metabolic advantage to CRCSC invasion. Moreover, hCINAP expression is positively correlated with the level of Y10-phosphorylated LDHA in CRC patients. This study identifies hCINAP as a potent modulator of metabolic reprogramming in CRCSCs and a promising drug target for CRC invasion and metastasis.
Whole blood transcriptome analysis reveals potential competition in metabolic pathways between negative energy balance and response to inflammatory challenge
Authors: Bouvier-Muller Juliette , Allain Charlotte , Tabouret Guillaume , Enjalbert Francis , Portes David , Noirot Céline , Rupp Rachel , Foucras Gilles 
Published: May 2017

AbstractNegative Energy Balance (NEB) is considered to increase susceptibility to mastitis. The objective of this study was to improve our understanding of the underlying mechanisms by comparing transcriptomic profiles following NEB and a concomitant mammary inflammation. Accordingly, we performed RNA-seq analysis of blood cells in energy-restricted ewes and control-diet ewes at four different time points before and after intra mammary challenge with phlogogenic ligands. Blood leucocytes responded to NEB by shutting down lipid-generating processes, including cholesterol and fatty acid synthesis, probably under transcriptional control of SREBF 1. Furthermore, fatty acid oxidation was activated and glucose oxidation and transport inhibited in response to energy restriction. Among the differentially expressed genes (DEGs) in response to energy restriction, 64 genes were also differential in response to the inflammatory challenge. Opposite response included the activation of cholesterol and fatty acid synthesis during the inflammatory challenge. Moreover, activation of glucose oxidation and transport coupled with the increase of plasma glucose concentration in response to the inflammatory stimuli suggested a preferential utilization of glucose as the energy source during this stress. Leucocyte metabolism therefore undergoes strong metabolic changes during an inflammatory challenge, which could be in competition with those induced by energy restriction.