bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients
Authors: Stephens Nathan A. , Skipworth Richard J. E. , Gallagher Iain J. , Greig Carolyn A. , Guttridge Denis C. , Ross James A. , Fearon Kenneth C. H. 
Published: April 2015

AbstractBackgroundIn order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.MethodsOne hundred seven patients (15 weight‐stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight‐loss of UGIC patients was 8.1 (9.3%). Cachexia was defined as weight‐loss ≥5%. Rectus abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real‐time–polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n = 52), forkhead box O transcription factors (n = 59), ubiquitin E3 ligases (n = 59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n = 59, as markers of autophagy), myosin heavy‐chain (MyHC, n = 54), dystrophin (n = 39), β‐dystroglycan (n = 52), and β‐sarcoglycan (n = 52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255 days (range 581–1955 days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non‐cachectic cancer patients; and (iii) cancer patients surviving ≤1 vs. >1 year post operatively.ResultsCancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P = 0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P = 0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P = 0.024]. β‐Dystroglycan levels were higher in cachectic compared with non‐cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P = 0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326 days, P = 0.023) and dystrophin levels (median 341 vs. 660 days, P = 0.008).ConclusionsThe present study has identified intramuscular protein level of β‐dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers.
Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure—relevance of inflammatory cytokines
Authors: Matsuo Yae , Gleitsmann Konstanze , Mangner Norman , Werner Sarah , Fischer Tina , Bowen T Scott , Kricke Angela , Matsumoto Yasuharu , Kurabayashi Masahiko , Schuler Gerhard , Linke Axel , Adams Volker 
Published: April 2015

AbstractBackgroundChronic heart failure (CHF) is commonly associated with muscle atrophy and increased inflammation. Irisin, a myokine proteolytically processed by the fibronectin type III domain containing 5 (FNDC5) gene and suggested to be Peroxisome proliferator‐activated receptor gamma coactivator (PGC)‐1α activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and/or angiotensin II (Ang‐II).MethodsSkeletal muscle FNDC5 mRNA/protein and PGC‐1α mRNA expression (arbitrary units) were analysed in: (i) rats with ischemic cardiomyopathy; (ii) mice injected with tumour necrosis factor‐α (TNF‐α) (24 h); (iii) mice infused with Ang‐II (4 weeks); and (iv) C2C12 myotubes exposed to recombinant cytokines or Ang‐II. Circulating TNF‐α, Ang‐II, and irisin was measured by ELISA.ResultsIschemic cardiomyopathy reduced significantly FNDC5 protein (1.3 ± 0.2 vs. 0.5 ± 0.1) and PGC‐1α mRNA expression (8.2 ± 1.5 vs. 4.7 ± 0.7). In vivo TNF‐α and Ang‐II reduced FNDC5 protein expression by 28% and 45%, respectively. Incubation of myotubes with TNF‐α, interleukin‐1ß, or TNF‐α/interleukin‐1ß reduced FNDC5 protein expression by 47%, 37%, or 57%, respectively, whereas Ang‐II had no effect. PGC‐1α was linearly correlated to FNDC5 in all conditions. In CHF, animals circulating TNF‐α and Ang‐II were significantly increased, whereas irisin was significantly reduced. A negative correlation between circulating TNF‐α and irisin was evident.ConclusionA reduced expression of skeletal muscle FNDC5 in ischemic cardiomyopathy is likely modulated by inflammatory cytokines and/or Ang‐II via the down‐regulation of PGC‐1α. This may act as a protective mechanism either by slowing the browning of adipocytes and preserving energy homeostasis or by regulating muscle atrophy.
Preparation of ALA‐loaded PLGA nanoparticles and its application in PDT treatment
Authors: Guan Yanping , Zhou Yi , Sheng Jie , Ying Jiang Zhong , Jumahan Halydan , Hu Yong 
Published: April 2015

AbstractBACKGROUNDCoaxial electrospray is an emerging technology to produce multilayer micro‐ and nano‐particles (NPs) with well controlled shape and size. ALA‐PDT is a fascinating technology used in the treatment for skin and other cancers. In this work, ALA‐loaded poly(lactide‐co‐glycolide) (PLGA) (PLGA‐ALA) NPs with high drug loading efficiency were produced via coaxial electrospray and used for the PDT treatment in HSC‐3 cells.RESULTSResults showed that 200–1000 nm PLGA‐ALA NPs with 60–75% ALA loading efficiency were successfully produced. ALA and PLGA were well integrated and no extra chemical reaction occurred during the electrospray. PLGA‐ALA NPs displayed a delayed release of ALA in PBS solution up to 7 days. A massive accumulation of PpIX in HSC‐3 cells happened after the incubation of PLGA‐ALA NPs. With light irradiation, these PLGA‐ALA NPs showed a remarkable cytotoxicity against HSC‐3 cells, leading to 40–70% cell death depending on the incubation dose.CONCLUSIONSCoaxial electrospraying is a facile method to prepare PLGA‐ALA NPs with high drug loading content and efficiency, and PLGA‐ALA NPs turned out to be an effective vehicle for delivering ALA to tumor cells. © 2015 Society of Chemical Industry
Short‐term prognostic factors for primary sclerosing cholangitis
Authors: Watanabe Takeo , Hirano Kenji , Tada Minoru , Isayama Hiroyuki , Mizuno Suguru , Arizumi Toshihiko , Toda Nobuo , Sugawara Yasuhiko , Kokudo Norihiro , Koike Kazuhiko 
Published: April 2015

AbstractBackgroundIt was recently reported that alkaline phosphatase (ALP) levels below 1.5 upper limit of normal (ULN) predicted better prognosis in primary sclerosing cholangitis (PSC). We evaluated whether ALP as well as other laboratory values were useful for the short‐term prognosis of PSC in a Japanese cohort.MethodsIn 78 patients with PSC (41 males and 37 females, mean onset age 41.9 years), the relationship between nine parameters (albumin, bilirubin, international normalized ratio of prothrombin time [PT‐INR], ALP, aspartate aminotransferase [AST], alanine aminotransferase [ALT], γ‐glutamyl transpeptidase [γ‐GTP], platelet, and calculated Model for End‐Stage Liver Disease [MELD] score), and liver related clinical endpoints (death due to liver failure, variceal bleeding, liver transplantation, and biliary carcinoma) were retrospectively examined. Using receiver operating characteristic (ROC) analysis, we investigated which parameter was useful for predicting the short‐term prognosis.ResultsAverage follow‐up period was 8.6 years. The endpoints were evaluated in 40 patients. Seven patients died of liver failure, three patients developed variceal bleeding, nine patients received liver transplantation from a living donor, 13 patients received certified brain‐dead liver transplantation, and eight patients developed biliary carcinoma. The parameters with an area under the curve (AUC) of more than 0.8 were albumin, bilirubin, PT‐INR, ALP, and MELD score. AUC for ALP was 0.85. The optimal cutoff value was 2.3 ULN. Despite the use or non‐use of ursodeoxycholic acid, short‐term prognosis of patients with an ALP level below 2.3 ULN was good.ConclusionsWe confirmed that keeping ALP low is associated with better short‐term prognosis in a Japanese cohort. In addition, Alb, Bil, PT‐INR, and MELD score were good predictors.
Main‐Chain Chiral Poly(2‐oxazoline)s: Influence of Alkyl Side‐Chain on Secondary Structure Formation in the Solid State
Authors: Bloksma Meta M. , Hendrix Marco M. R. M. , Rathgeber Silke , Schubert Ulrich S. , Hoogenboom Richard 
Published: April 2015

SummaryThe influence of the side‐chains of main‐chain chiral poly(2‐oxazoline) s on their thermal properties was investigated using differential scanning calorimetry (DSC) and the nature of the obtained melting endotherms was further investigated by thermal annealing of the polymers. Poly(R‐2‐ethyl‐4‐ethyl‐2‐oxazoline) (p‐R‐EtEtOx) was found to be amorphous, while polymers with longer side‐chains are semi‐crystalline. Previously we reported that the chirally ordered crystals of poly(R‐2‐butyl‐4‐ethyl‐2‐oxazoline) (p‐R‐BuEtOx) have a high melting temperature of more than 200 °C. in this work we demonstrate that elongation of the side‐chains from butyl to octyl results in a decrease in the crystallization rate and melting temperature suggesting that the chirally ordered crystals of p‐R‐BuEtOx are based on close packing of the main‐chain enhancing diploar interactions between the tertiary amide moieties. Crystallizaiton of chiral polymers with longer side‐chains results may then be driven by close packing of the side‐chains. This is supported by the observation that further elongation of the side‐chain length increases the crystallization rate. Moerover, an additional melting endotherm appears for these polymers at a lower temperature upon annealing ascribed to a dual crystal size population. Circular dichroism (CD) measurements of the semi‐crystalline main‐chain chiral polymer films revealed the presence of chirally ordered crystals while X‐ray diffraction (XRD) patterns revealed a closer packing of the chiral poly(2‐alkyl‐2‐oxazoline) s compared to the non‐chiral polymers, suggested to result form the chiral ordering in the crystals. Grazing incidence wide angle x‐ray scattering (GIWAXS) patterns indicated that the chiral crystals of p‐R‐BuEtOx do not form a helical structure, however, the substrate does influence the type of structure formed.
Nanosilica‐immobilized UV absorber: synthesis and photostability of polyolefins
Authors: Liu Peng , Gao Chong , Han Chunchun , Tang Hanying , Wang Feng , Ding Yanfen , Zhang Shimin , Yang Mingshu 
Published: April 2015

AbstractA nanosilica‐immobilized UV absorber (SiO2‐APTMS‐UVA) was prepared by the following methods: the fumed nanosilica was first modified with an aminosilane coupling agent 3‐aminopropyltrimethoxysilane (APTMS) and then reacted with hydroxy‐benzoyl chloride. Several measurements confirmed that the UV absorber was chemically immobilized on the surface of the nanosilica. SEM observation showed that SiO2‐APTMS‐UVA was homogeneously dispersed in the matrix of low density polyethylene (LDPE) and polypropylene (PP). The photo‐degradation of the nanocomposites was evaluated by an accelerated aging test. It was found that the SiO2‐APTMS‐UVA has a great effect on preventing the degradation of LDPE or PP under UV exposure. © 2015 Society of Chemical Industry
Convectively coupled equatorial‐wave diagnosis using three‐dimensional normal modes
Authors: Castanheira José M. , Marques Carlos A. F. 
Published: April 2015

A new methodology for the diagnosis of convectively coupled equatorial waves (CCEWs) is presented. It is based on a pre‐filtering of the geopotential and horizontal wind, using three‐dimensional (3D) normal mode functions of the adiabatic linearized equations of a resting atmosphere, followed by a space–time spectral analysis to identify the spectral regions of coherence.The methodology permits a direct detection of various types of equatorial wave, compares the dispersion characteristics of the coupled waves with the theoretical dispersion curves and allows an identification of which vertical modes are more involved in the convection. Moreover, the proposed methodology is able to show the existence of free dry waves and moist coupled waves with a common vertical structure, which is in conformity with the effect of convective heating/cooling on the effective static stability, as deduced from the gross moist stability concept. The methodology is also sensitive to wave interactions.The methodology has been applied to the ERA‐Interim horizontal wind and geopotential height fields and to the interpolated outgoing long‐wave radiation (OLR) data produced by the National Oceanic and Atmospheric Administration. The results obtained provide examples of the aforementioned effects.
Agglomeration and the choice between acquisitions and alliances: An information economics perspective
Authors: McCann Brian T. , Reuer Jeffrey J. , Lahiri Nandini 
Published: April 2015

Research summary: This research extends agglomeration theory by joining it with information economics research to better understand the determinants of firms' organizational governance choices. We argue that co‐location in a common geographic cluster fosters lower levels of information asymmetry between exchange partners and thus leads firms to employ acquisitions rather than alliances for their external corporate development activities. We further extend agglomeration theory by arguing that the impact of sharing a cluster location on acquisitions versus alliances strengthens with the level and dissimilarity of the exchange partners' knowledge‐based resources as well as with the intra‐cluster geographic proximity of the partners. Evidence from a sample of over 1,100 alliance and acquisition transactions in the U.S. semiconductor industry provides support for our hypotheses.Managerial summary: This paper investigates the role of geographical clustering for firms' external corporate development activities in acquisitions and alliances. We explain how better information is likely to be available among firms co‐located in the same cluster. This suggests that managers should have less need to use alliances over acquisitions as a means of reducing the risk of adverse selection (e.g., overpaying for acquisitions). Our investigation of over 1,100 transactions in the U.S. semiconductor industry shows that common cluster co‐location increases the probability of acquisition relative to alliance. Our arguments and evidence also indicate that the information‐related benefits of cluster co‐location are even more impactful when the parties have more divergent technology bases, possess larger stocks of knowledge‐based resources, or are located in closer geographic proximity. Copyright © 2015 John Wiley & Sons, Ltd.
Brief Report: Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure
Authors: Hashem Sherin I. , Perry Cynthia N. , Bauer Matthieu , Han Sangyoon , Clegg Stacey D. , Ouyang Kunfu , Deacon Dekker C. , Spinharney Mary , Panopoulos Athanasia D. , Izpisua Belmonte Juan Carlos , Frazer Kelly A. , Chen Ju , Gong Qiuming , Zhou Zhengfeng , Chi Neil C. , Adler Eric D. 
Published: April 2015

Abstract
Danon disease is a familial cardiomyopathy associated with impaired autophagy due to mutations in the gene encoding lysosomal-associated membrane protein type 2 (LAMP-2). Emerging evidence has highlighted the importance of autophagy in regulating cardiomyocyte bioenergetics, function, and survival. However, the mechanisms responsible for cellular dysfunction and death in cardiomyocytes with impaired autophagic flux remain unclear. To investigate the molecular mechanisms responsible for Danon disease, we created induced pluripotent stem cells (iPSCs) from two patients with different LAMP-2 mutations. Danon iPSC-derived cardiomyocytes (iPSC-CMs) exhibited impaired autophagic flux and key features of heart failure such as increased cell size, increased expression of natriuretic peptides, and abnormal calcium handling compared to control iPSC-CMs. Additionally, Danon iPSC-CMs demonstrated excessive amounts of mitochondrial oxidative stress and apoptosis. Using the sulfhydryl antioxidant N-acetylcysteine to scavenge free radicals resulted in a significant reduction in apoptotic cell death in Danon iPSC-CMs. In summary, we have modeled Danon disease using human iPSC-CMs from patients with mutations in LAMP-2, allowing us to gain mechanistic insight into the pathogenesis of this disease. We demonstrate that LAMP-2 deficiency leads to an impairment in autophagic flux, which results in excessive oxidative stress, and subsequent cardiomyocyte apoptosis. Scavenging excessive free radicals with antioxidants may be beneficial for patients with Danon disease. In vivo studies will be necessary to validate this new treatment strategy. Stem Cells 2015;33:2343–2350
Crif1 Promotes Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells After Irradiation by Modulating the PKA/CREB Signaling Pathway
Authors: Zhang Xi , Xiang Lixin , Ran Qian , Liu Yao , Xiang Yang , Xiao Yanni , Chen Li , Li Fengjie , Zhong Jiang F. , Li Zhongjun 
Published: April 2015

Abstract
Dysfunction of the hematopoietic microenvironment is the main obstacle encountered during hematopoiesis reconstruction in patients with acute hematopoietic radiation syndrome. Bone marrow mesenchymal stem cells (BM-MSCs) play a crucial supporting role in hematopoiesis by maintaining the balance between adipogenic and osteogenic differentiation. In this study, we found that irradiation decreased the colony-forming efficiency of BM-MSCs and impaired the balance between adipogenic and osteogenic differentiation. Following irradiation, BM-MCSs became strongly predisposed to adipogenesis, as evidenced by increased oil red O staining and elevated mRNA and protein levels of the adipogenic markers and transcription factors PPARγ and AP2. Overexpression of the essential adipogenesis regulator Crif1 in BM-MSCs promoted adipogenesis after irradiation exposure by upregulating adipogenesis-related genes, including C/EBPβ, PPARγ, and AP2. We found that Crif1 promoted the phosphorylation of cAMP response element binding protein (CREB) through direct interaction with protein kinase A (PKA)-α. Phosphorylation of CREB was inhibited in Crif1-knockdown BM-MSCs even in the presence of a PKA agonist (db-cAMP) and could be suppressed in Crif1-overexpressing BM-MSCs by a PKAα inhibitor (H-89). These results suggest that Crif1 is an indispensable regulator of PKAα cat that modulates the PKA/CREB signaling pathway to promote adipogenic differentiation of BM-MSCs after irradiation. Stem Cells 2015;33:1915–1926
Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer
Authors: Weiss Andrea , Ding Xianting , van Beijnum Judy R. , Wong Ieong , Wong Tse J. , Berndsen Robert H. , Dormond Olivier , Dallinga Marchien , Shen Li , Schlingemann Reinier O. , Pili Roberto , Ho Chih-Ming , Dyson Paul J. , van den Bergh Hubert , Griffioen Arjan W. , Nowak-Sliwinska Patrycja 
Published: April 2015

AbstractDrug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation (p < 0.001), but not migration of endothelial cells, and forced enhanced numbers of endothelial cells to undergo apoptosis (p < 0.01). Successful translation of this drug combination was achieved in two preclinical in vivo tumor models. Tumor growth was inhibited synergistically and significantly (p < 0.05 and p < 0.01, respectively) using reduced drug doses as compared to optimal single-drug concentrations. At the applied conditions, single-drug monotherapies had no or negligible activity in these models. We suggest that FSC can be used for rapid identification of effective, reduced dose, multi-drug combinations for the treatment of cancer and other diseases.
Changing the Environmental Behaviour of Small Business Owners: The Business Case
Authors: Walker Beth , Redmond Janice 
Published: April 2015

AbstractThe importance of the environment is something of a cracked record to many small business owners, as historically any calls to business to change or improve their practices or behaviours were from the ‘environmental’ or ‘green’ perspective, rather than from a business perspective. As a consequence, many small businesses have simply tuned out. This research sought to identify the impact of an education intervention program that encouraged better environmental management practices and provided practical assistance to the businesses. The research was designed to test the effectiveness of the program and record any changes that occurred in the businesses over the duration of the project. To measure changes, it included a pre- and post-intervention survey. Overall, there was an increased awareness in most of the businesses in regard to environmental issues. Participants from many of the businesses also expressed positive changes to both behaviours and attitudes to environmental issues. This demonstrated the value of the program, and also highlighted the challenge to engage small business, even when a business case is apparent, given the cost of implementing this type of intensive and personalised assistance.
Whole-exome sequencing and its impact in hereditary hearing loss
Authors: ATIK TAHIR , BADEMCI GUNEY , DIAZ-HORTA OSCAR , BLANTON SUSAN H. , TEKIN MUSTAFA 
Published: April 2015

SummaryNext-generation sequencing (NGS) technologies have played a central role in the genetic revolution. These technologies, especially whole-exome sequencing, have become the primary tool of geneticists to identify the causative DNA variants in Mendelian disorders, including hereditary deafness. Current research estimates that 1% of all human genes have a function in hearing. To date, mutations in over 80 genes have been reported to cause nonsyndromic hearing loss (NSHL). Strikingly, more than a quarter of all known genes related to NSHL were discovered in the past 5 years via NGS technologies. In this article, we review recent developments in the usage of NGS for hereditary deafness, with an emphasis on whole-exome sequencing.