bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexibler Einwanderer
Authors: Winkelmann Carola
Published: April 2016

Gewässerökologie in Elbe und Rhein: Der Große Höckerflohkrebs, auch „killer shrimp”︁ genannt, verfolgt offenbar verschiedene Überlebensstrategien. Je nach Umgebung und Umweltbedingungen kann er sein Jagd‐ und Fressverhalten ändern.
Kein Segen, nirgends
Authors: Behrends Andrea
Published: April 2016

Die alte landwirtschaftliche Produktionsweise mit der neuen Erdölförderung zu verbinden — darauf setzt die politische Klasse im zentralafrikanischen Tschad. Doch die Erdölwirtschaft fordert einen hohen Preis: vergiftete Böden, ausgehöhltes Landrecht und gesellschaftliche Verwerfungen. Ethnologen beobachten ein Land im sozialen und kulturellen Umbruch.
Verantwortete Freiheit
Authors: Strohschneider Peter
Published: April 2016

Die kritische Selbstreflexion der eigenen Möglichkeiten und Begrenztheiten ist eine Daueraufgabe für jeden Einzelnen im Wissenschaftssystem wie für das System als Ganzes — auch und gerade in Zeiten immer schnellerer Veränderungen in der Wissenschaft und ihren Umgebungen. Eine Wortmeldung aus Anlass der diesjährigen Verleihung der Leibniz‐Preise.
Der Patron hätte seine Freude gehabt
Authors: Finetti Marco
Published: April 2016

Auch ohne Exzellenzinitiative im Fokus — von „exzellenten Preis‐Leistungs‐Verhältnissen”︁ einst und jetzt war bei der Festveranstaltung gleich mehrfach und mit Fug und Recht die Rede.
Im Steigflug
Authors: Radespiel Rolf
Published: April 2016

Lärmarme Verkehrsflugzeuge mit Kurzstart‐ und ‐landefähigkeiten — ist das nur ein Traum? Innovative Hochauftriebssysteme sollen helfen, maßgeschneiderte Eigenschaften und effiziente Technologien zu schaffen. Dafür arbeiten Ingenieurwissenschaftler aus Flugphysik, Materialwissenschaften und Simulationstechnik Hand in Hand.
Lentivirus‐mediated somatic recombination and development of a novel mouse model for sporadic colorectal cancer
Authors: Vaish Vivek , Kim Joohwee , Shim Minsub
Published: April 2016

In this study, we have developed a novel mouse model for sporadic colorectal cancer (CRC) by utilizing APC conditional knockout (ApcCKO) mouse and lentivirus encoding Cre recombinase and a reporter gene (EGFP or LacZ). Lentiviral transduction of colonic crypt stem cells allowed for the long‐term expression of reporter gene as well as excision of floxed Apc alleles, which resulted in tumor development. Tumors represented adenoma stages along with the nuclear accumulation of β‐catenin. Loss of E‐cadherin at the cellular junctions and strong expression of Vimentin suggested the sign of active epithelial‐mesenchymal transition. Moreover, nuclear staining of Ki67 inside epithelial cells of aberrant crypts demonstrated their higher proliferative nature. Erratic downstream signaling of activated Wnt/β‐catenin, AKT/mTOR, and Notch pathways provided strong evidence towards the higher proliferative index of epithelial cells inside the aberrant crypts. These results do recapitulate the findings of previous APC mutant mouse models. Our model represents sporadic CRC more precisely as (i) tumors result from somatic mutations but not from germline; (ii) tumors develop in colon not in small intestine; (iii) few tumors develop at the distal end of colons. Additionally, our model allows for the long‐term expression of the gene(s), which get integrated into the host cell genome and provides an ability to track the tumor growth. © 2016 Wiley Periodicals, Inc.
Improved Halogenation of Methyl Aromatics and Methyl Heteroaromatics: Unexpected Reactivity of Tetrahalogeno‐diphenylglycolurils
Authors: Moretti Florian , Poisson Guillaume , Marsura Alain
Published: April 2016

1,3,4,6‐Tetrachloro (TCDGU) and 1,3,4,6‐tetrabromo‐3α,6α‐diphenylglycolurils smooth halogen oxidizers have been exploited in a new direction as reagents for free radical substitution toward someN‐halosuccinimide nonreactivebis‐heterocycles. An unexpected selectivity and reactivity were observed with methyl benzenes, methyl heterocycles, and methyl‐bis‐heterocycles of interest. A chemometric study has been performed to optimize five independent factors of the chlorination reaction with TCDGU. The predictive model was established either for the halogenation conversion and the ratio of monochlorination.
Analysis of Consumer Value Using Semantic Network: The Comparison of Hierarchical and Nonhierarchical Value Structures
Authors: Kim Ga‐Won , Hyoun Lim Ji , Hwan Yun Myung
Published: April 2016

This study compares the value structure of consumers derived from a nonhierarchical method that only requires grouping similar components and a hierarchical method that needs additional steps to classify components into the levels of abstraction, using semantic network analysis. The overall process of understanding consumers’ value structure consists of data collection, data structuring, and network analysis using UCINET 6.0. A case study was conducted to identify the value structure of teenage Internet use behavior. Based on the relative ranking of words with the smallest farness from others, the nonhierarchical method showed “beauty” as the key value of teenagers, while the hierarchical method revealed “warm relationship” as the critical value in their use of the Internet. This nonhierarchical method showed the ability to elicit more diverse values, depending on the characteristics of consumer groups when compared with conventional hierarchical method. © 2016 Wiley Periodicals, Inc.
Costs of hospital services in Jordan
Authors: Hammad Eman A , Fardous Taissir , Abbadi Ibrahim
Published: April 2016

Background

Policy makers are on quest for estimates of health costs to achieve maximum efficiency and sustainability. In Jordan, there is a scarcity of information on hospital service costs.

Aim

The purpose of this study was to estimate the direct cost of hospital services in one of the biggest public hospitals in Amman, Jordan.

Methods

A retrospective analysis forms a 400‐bed public urban hospital. Costs were estimated in Jordanian dinars (JD) (exchange rate was US$1.41).

Results

Inpatient costs contributed to 50% of all costs whilst outpatient clinics consumed 17%. Average cost per admission was JD 481.6 (US$674.2), JD 106.7 (US$149.3) per inpatient day and JD 63.1 (US$88.3) per bed day. The average cost per visit to emergency room was JD 14.1 s (US$19.7). Cost per visit to ambulatory care services ranged between JD 37.3 and 473 (US$52.6–662.2). The average cost per surgery was JD 322.1 (US$454.2).

Conclusions

With high health costs, areas for improvements in efficiency and cost savings must be identified and discussed with managers and policy makers. A larger‐scale study is advocated to understand the costs of various health providers such as military, teaching and private hospitals.
Identification of changes in floods and flood regimes in Canada using a peaks over threshold approach
Authors: Burn Donald H. , Whitfield Paul H. , Sharif Mohammed
Published: April 2016

Recent flood events in Canada have led to speculation that changes in flood behaviour are occurring; these changes have often been attributed to climate change. This paper examines flood data for a collection of 132 gauging stations in Canada. All of these watersheds are part of the Canadian Reference Hydrometric Basin Network (RHBN), a group of gauging stations specifically assembled to assist in the identification of the impacts of climate change. The RHBN stations are considered to have good quality data and were screened to avoid the influences of regulation, diversions, or land use change. Daily flow data for each watershed are used to derive a peaks over threshold (POT) dataset. Several measures of flood behaviour are examined based on the POT data, which afford a more in‐depth analysis of flood behaviour than can be obtained using annual maxima data. Analysis is conducted for four time periods ranging from 50 to 80 years in duration; the latter period results in a much smaller number of watersheds that have data for the period. The changes in flood responses of the watersheds are summarized by grouping the watersheds by size (small, medium, and large) and also by hydrologic regime (nival, mixed, and pluvial). The results provide important insights into the nature of the changes that are occurring in flood regimes of Canadian rivers, which include more flood exceedances, reduced maximum flood exceedance magnitudes for snowmelt events, and earlier flood events. Copyright © 2016 John Wiley & Sons, Ltd.
Comparison of methods for quantifying surface sublimation over seasonally snow‐covered terrain
Authors: Sexstone Graham A. , Clow David W. , Stannard David I. , Fassnacht Steven R.
Published: April 2016

Snow sublimation can be an important component of the snow‐cover mass balance, and there is considerable interest in quantifying the role of this process within the water and energy balance of snow‐covered regions. In recent years, robust eddy covariance (EC) instrumentation has been used to quantify snow sublimation over snow‐covered surfaces in complex mountainous terrain. However, EC can be challenging for monitoring turbulent fluxes in snow‐covered environments because of intensive data, power, and fetch requirements, and alternative methods of estimating snow sublimation are often relied upon. To evaluate the relative merits of methods for quantifying surface sublimation, fluxes calculated by the EC, Bowen ratio–energy balance (BR), bulk aerodynamic flux (BF), and aerodynamic profile (AP) methods and their associated uncertainty were compared at two forested openings in the Colorado Rocky Mountains. Biases between methods are evaluated over a range of environmental conditions, and limitations of each method are discussed. Mean surface sublimation rates from both sites ranged from 0.33 to 0.36 mm day−1, 0.14 to 0.37 mm day−1, 0.10 to 0.17 mm day−1, and 0.03 to 0.10 mm day−1 for the EC, BR, BF and AP methods, respectively. The EC and/or BF methods are concluded to be superior for estimating surface sublimation in snow‐covered forested openings. The surface sublimation rates quantified in this study are generally smaller in magnitude compared with previously published studies in this region and help to refine sublimation estimates for forested openings in the Colorado Rocky Mountains. Copyright © 2016 John Wiley & Sons, Ltd.
Understanding fen hydrology across multiple scales
Authors: Sampath Prasanna Venkatesh , Liao Hua‐Sheng , Curtis Zachary Kristopher , Herbert Matthew E. , Doran Patrick J. , May Christopher A. , Landis Douglas A. , Li Shu‐Guang
Published: April 2016

Fens, which are among the most biodiverse of wetland types in the USA, typically occur in glacial landscapes characterized by geo‐morphologic variability at multiple spatial scales. As a result, the hydrologic systems that sustain fens are complex and not well understood. Traditional approaches for characterizing such systems use simplifying assumptions that cannot adequately capture the impact of variability in geology and topography. In this study, a hierarchical, multi‐scale groundwater modelling approach coupled with a geologic model is used to understand the hydrology of a fen in Michigan. This approach uses high‐resolution data to simulate the multi‐scale topographic and hydrologic framework and lithologic data from more than 8500 boreholes in a statewide water well database to capture the complex geology. A hierarchy of dynamically linked models is developed that simulates groundwater flow at all scales of interest and to delineate the areas that contribute groundwater to the fen. The results show the fen receiving groundwater from multiple sources: an adjacent wetland, local recharge, a nearby lake and a regional groundwater mound. Water from the regional mound flows to an intermediate source before reaching the fen, forming a ‘cascading’ connection, while other sources provide water through ‘direct’ connections. The regional mound is also the source of water to other fens, streams and lakes in this area, thus creating a large, interconnected hydrologic system that sustains the entire ecosystem. In order to sustainably manage such systems, conservation efforts must include both site‐based protection and management, as well as regional protection and management of groundwater source areas. Copyright © 2016 John Wiley & Sons, Ltd.
Eosinophil protein X and childhood asthma: A systematic review and meta‐analysis
Authors: Klonoff‐Cohen Hillary , Polavarapu Mounika
Published: April 2016

Background: There are no reference guidelines for health care providers regarding appropriate use and interpretation of urine eosinophil protein X (u‐EPX) in clinical practice. Currently, there are no clear‐cut clinical or laboratory parameters to diagnose asthma in young children. Objective: In this study, we (1) systematically reviewed and qualitatively appraised the epidemiological evidence to determine diagnostic u‐EPX cut points for pediatric asthma, and (2) performed a meta‐analysis to provide u‐EPX estimates for diagnosing pediatric asthma. Methods: Research articles in literature were identified from PubMed/Medline and Web of Science databases from 1966 to August 2015. Children <18 years of age were included. Both serum and urine EPX were included. Twenty‐seven studies met the inclusion criteria for the systematic review and nine studies for the meta‐analysis. Details regarding EPX analyses, treatment efficacy, and outcomes were assessed. For meta‐analyses, effect estimates were abstracted using standardized means. Results: Over 70% of studies found a significant relationship between u‐EPX and childhood asthma. There was 1.94 times higher standardized means of u‐EPX among acute asthmatics compared to healthy controls (confidence interval [CI]: 1.67–2.22). Similarly, the difference in standardized means between asymptomatic asthmatics and healthy controls was 1.58 times higher (CI: 1.27–1.88). Conclusions and Clinical Relevance: Despite differences in sample sizes, EPX processing and measurement, and ages of children, a consistent trend of higher EPX levels with childhood asthma was revealed.
Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates
Authors: Weeratna Risini D. , Chikh Ghania , Zhang Lu , Fraser James D. , Thorn Jennifer M. , Merson James R. , McCluskie Michael J. , Champion Brian R. , Davis Heather L.
Published: April 2016

The anti‐human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre‐existing IgE levels, and frequent dosing (q2–4 weeks). A vaccine inducing anti‐IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide‐conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non‐human primates, and demonstrate the induction of anti‐peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.
The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status
Authors: Baglia Michelle L. , Zheng Wei , Li Honglan , Yang Gong , Gao Jing , Gao Yu‐Tang , Shu Xiao‐Ou
Published: April 2016

Soy food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy food intake and breast cancer risk, we measured usual soy food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40–70 years, recruited to the Shanghai Women's Health Study (1996–2000). After a median follow‐up of 13.2 years (range: 0.01–15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus first quintile soy protein intake = 0.78; 95% confidence interval (CI):0.63–0.97]. The association was predominantly seen in premenopausal women (HR = 0.46; 95% CI:0.29‐0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in postmenopausal women (HR = 0.72; 95% CI:0.53–0.96) and decreased risk of ER−/PR− breast cancer in premenopausal women (HR = 0.46; 95% CI:0.22–0.97). The soy association did not vary by human epidermal growth factor‐2 (HER2) status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR = 0.53; 95% CI: 0.32–0.88; comparing third vs. first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR = 0.63; 95% CI: 0.43–0.91). Our study suggests that hormonal status, menopausal status and time window of exposure are important factors influencing the soy‐breast cancer association.
h‐Prune is associated with poor prognosis and epithelial–mesenchymal transition in patients with colorectal liver metastases
Authors: Hashimoto Masakazu , Kobayashi Tsuyoshi , Tashiro Hirotaka , Arihiro Koji , Kikuchi Akira , Ohdan Hideki
Published: April 2016

The prognosis of patients with colorectal liver metastases (CRLM) remains low despite advances in chemotherapy and surgery. The expression of h‐prune (human homolog of Drosophila prune protein; HGNC13420), an exopolyphosphatase, is correlated with progression and aggressiveness in several cancers and promotes migration and invasion. We investigated the role of h‐prune in CRLM. To investigate the role of h‐prune, immunohistochemical analysis for h‐prune was performed in 87 surgically resected specimens of CRLM obtained between 2001 and 2009 at the Hiroshima University Hospital. Immunohistochemical analysis revealed positive staining for h‐prune in 24 (28%) cases. The overall survival rate was significantly lower in h‐prune‐positive cases than in h‐prune‐negative cases (p = 0.003). Multivariate analysis showed that h‐prune positivity was the only independent factor related to poor overall survival of patients after curative hepatectomy of CRLM. In vitro and in vivo, h‐prune‐knocked‐down and h‐prune‐overexpressing cells were analyzed. In vitro, h‐prune was associated with increased cell motility and upregulation of epithelial–mesenchymal transition (EMT) markers. In a mouse model, h‐prune was associated with invasion of the tumor and distant metastases. In summary, h‐prune expression is a useful marker to identify high‐risk patients for resectable colorectal liver metastasis. h‐Prune expression is necessary for cancer cell motility and EMT and is associated with liver and lung metastasis in colorectal cancer cells. h‐Prune could be a new prognostic marker and molecular target for CRLM.
A novel approach for targeted elimination of CSPG4‐positive triple‐negative breast cancer cells using a MAP tau‐based fusion protein
Authors: Amoury Manal , Mladenov Radoslav , Nachreiner Thomas , Pham Anh‐Tuan , Hristodorov Dmitrij , Di Fiore Stefano , Helfrich Wijnand , Pardo Alessa , Fey Georg , Schwenkert Michael , Thepen Theophilus , Kiessling Fabian , Hussain Ahmad F. , Fischer Rainer , Kolberg Katharina , Barth Stefan
Published: April 2016

Chondroitin sulfate proteoglycan 4 (CSPG4) has been identified as a highly promising target antigen for immunotherapy of triple‐negative breast cancer (TNBC). TNBC represents a highly aggressive heterogeneous group of tumors lacking expression of estrogen, progesterone and human epidermal growth factor receptor 2. TNBC is particularly prevalent among young premenopausal women. No suitable targeted therapies are currently available and therefore, novel agents for the targeted elimination of TNBC are urgently needed. Here, we present a novel cytolytic fusion protein (CFP), designated αCSPG4(scFv)‐MAP, that consists of a high affinity CSPG4‐specific single‐chain antibody fragment (scFv) genetically fused to a functionally enhanced form of the human microtubule‐associated protein (MAP) tau. Our data indicate that αCSPG4(scFv)‐MAP efficiently targets CSPG4+ TNBC‐derived cell lines MDA‐MB‐231 and Hs 578T and potently inhibits their growth with IC50 values of ∼200 nM. Treatment with αCSPG(scFv)‐MAP resulted in induction of the mitochondrial stress pathway by activation of caspase‐9 as well as endonuclease G translocation to the nucleus, while induction of the caspase‐3 apoptosis pathway was not detectable. Importantly, in vivo studies in mice bearing human breast cancer xenografts revealed efficient targeting to and accumulation of αCSPG4(scFv)‐MAP at tumor sites resulting in prominent tumor regression. Taken together, this preclinical proof of concept study confirms the potential clinical value of αCSPG4(scFv)‐MAP as a novel targeted approach for the elimination of CSPG4‐positive TNBC.
Host genetic influence on papillomavirus‐induced tumors in the horse
Authors: Staiger Elizabeth A. , Tseng Chia T. , Miller Donald , Cassano Jennifer M. , Nasir Lubna , Garrick Dorian , Brooks Samantha A. , Antczak Douglas F.
Published: April 2016

The common equine skin tumors known as sarcoids have been causally associated with infection by bovine papillomavirus (BPV). Additionally, there is evidence for host genetic susceptibility to sarcoids. We investigated the genetic basis of susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270 controls genotyped on a genome‐wide platform and two custom panels. A Genome Wide Association Study (GWAS) identified candidate regions on six chromosomes. Bayesian probability analysis of the same dataset verified only the regions on equine chromosomes (ECA) 20 and 22. Fine mapping using custom‐produced SNP arrays for ECA20 and ECA22 regions identified two marker loci with high levels of significance: SNP BIEC2‐530826 (map position 32,787,619) on ECA20 in an intron of the DQA1 gene in the Major Histocompatibility Complex (MHC) class II region (p = 4.6e‐06), and SNP BIEC2‐589604 (map position 25,951,536) on ECA22 in a 200 kb region containing four candidate genes: PROCR, EDEM2, EIF6 and MMP24 (p = 2.14e‐06). The marker loci yielded odds ratios of 5.05 and 4.02 for ECA20 and ECA22, respectively. Associations between genetic MHC class II variants and papillomavirus‐induced tumors have been reported for human papillomavirus and cottontail rabbit papillomavirus infections. This suggests a common mechanism for susceptibility to tumor progression that may involve subversion of the host immune response. This study also identified a genomic region other than MHC that influenced papillomavirus‐induced tumor development in the studied population.
Induction of antigen‐specific TH9 immunity accompanied by mast cell activation blocks tumor cell engraftment
Authors: Abdul‐Wahid Aws , Cydzik Marzena , Prodeus Aaron , Alwash Mays , Stanojcic Mile , Thompson Megan , Huang Eric H.‐B. , Shively John E. , Gray‐Owen Scott D. , Gariépy Jean
Published: April 2016

The engraftment of circulating cancer cells at distal sites represents a key step in the metastatic cascade, yet remains an unexplored target for therapeutic intervention. In this study, we establish that a vaccination strategy yielding an antigen‐specific TH9 response induces long term host surveillance and prevents the engraftment of circulating cancer cells. Specifically, we show that vaccination with a recombinant CEA IgV‐like N domain, formulated with the TLR3 ligand poly I:C, elicits a CEA‐specific TH9 response, wherein IL‐9 secreting TH cells act in concert with CEA N domain‐specific antibodies as well as activated mast cells in preventing tumor cell engraftment. The development of this immune response was dependent on TLR3, since interference with the TLR3‐dsRNA complex formation led to a reduction in vaccine‐imparted protection and a shift in the resulting immune response toward a TH2 response. These findings point to the existence of an alternate tumor targeting immune mechanism that can be exploited for the purpose of developing vaccine therapies targeting tumor dissemination and engraftment.
Patients' perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy
Authors: Kendel Friederike , Helbig Lukas , Neumann Konrad , Herden Jan , Stephan Carsten , Schrader Mark , Gaissmaier Wolfgang
Published: April 2016

Treatment choice for localized prostate cancer (PCa) is a controversial issue, and mortality risk is probably the most decisive factor in this regard. The study aimed to compare prostate‐cancer‐specific mortality risk estimates for different treatment options assigned by patients managed with active surveillance (AS), radical prostatectomy (RP) and patients who had discontinued AS (DAS). Patients initially managed with AS or RP (N = 370) were matched according to length of therapy. All patients completed mailed questionnaires assessing their mortality risk estimates (in %) and prostate‐cancer‐specific anxiety. Differences in risk estimates among the three treatment groups were analyzed using ANOVA, relationships of clinical and psychosocial variables with risk estimates using standard multiple regression. In all treatment groups, the prostate‐ cancer‐specific mortality risk was overestimated. This applied whether it was the patient's own treatment or the alternative treatment option. RP patients assigned a mortality risk to AS that was almost three times higher than that assigned to RP (50.9 ± 25.0 vs. 17.8 ± 19.7, d = 1.48; p < 0.001). Anxiety was significantly associated with risk estimates for AS (p = 0.008) and RP (p = 0.001). Compared with clinical data that suggest that the prostate‐cancer‐specific mortality risk for AS is low and does not significantly differ from that for RP, patients strongly overestimated the mortality risk. This was most markedly so in RP patients, who drastically overestimated the benefits of RP compared to the risk of AS. This overestimation could increase overtreatment and should therefore be corrected by better patient education.
Early sorafenib‐related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients
Authors: Zhao Yan , Li Hailiang , Bai Wei , Liu Jueshi , Lv Weifu , Sahu Sonia , Guan Sheng , Qin Xiao , Wang Wenhui , Ren Weixin , Mu Wei , Guo Weidong , Gu Shanzhi , Ma Yilong , Yin Zhanxin , Guo Wengang , Wang Wenjun , Wang Yongji , Duran Rafael , Fan Daiming , Zhang Zhuoli , Han Guohong
Published: April 2016

The purpose of our study was to test the hypothesis that sorafenib‐related dermatologic adverse events (AEs) as an early biomarker can predict the long‐term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE‐S). The intermediate‐stage hepatocellular carcinoma patients who received either TACE‐S or TACE‐alone treatment were consecutively included into analysis. In the TACE‐S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE‐S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval‐CI: 1.3–2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0–30.8) among responders treated with TACE‐S vs.18.3 months (95% CI: 14.5–22.1) among those who received TACE‐alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4–21.8) in the TACE‐S group, a duration that was significantly longer than that in the TACE‐alone group [5 months (95% CI: 6.4–13.3), p = 0.014]. This study demonstrated that sorafenib‐related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE‐S therapy. Sorafenib‐related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE‐S in future randomized controlled trials.
First‐line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors
Authors: Vivaldi Caterina , Caparello Chiara , Musettini Gianna , Pasquini Giulia , Catanese Silvia , Fornaro Lorenzo , Lencioni Monica , Falcone Alfredo , Vasile Enrico
Published: April 2016

FOLFIRINOX is a standard first‐line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty‐seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated. After a median follow up of 30 months, median PFS and OS were 8.0 months (95% CI 6.19–9.81) and 12 months (95% CI 9.75–14.25), respectively. Response rate was 38.6%, while disease‐control rate 72.2%. At multivariate analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42–3.59) and neutrophil‐lymphocyte ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38–4.25) were associated with poorer OS. We categorized 119 pts with complete available data as good‐risk (0 factors, 38 pts), intermediate‐risk (1 factor, 49 pts) and poor‐risk (≥2 factors, 32 pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months, respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of aPC pts treated with FOLFOXIRI is influenced by easily available factors: our analysis revealed ECOG PS, liver metastases and NLR as the most important predictors of survival. These factors could be helpful for treatment decision and clinical trial design.
Influence of the large–small split effect on strategy choice in complex subtraction
Authors: Xiang Yan hui , Wu Hao , Shang Rui hong , Chao Xiaomei , Ren Ting ting , Zheng Li ling , Mo Lei
Published: April 2016

Two main theories have been used to explain the arithmetic split effect: decision‐making process theory and strategy choice theory. Using the inequality paradigm, previous studies have confirmed that individuals tend to adopt a plausibility‐checking strategy and a whole‐calculation strategy to solve large and small split problems in complex addition arithmetic, respectively. This supports strategy choice theory, but it is unknown whether this theory also explains performance in solving different split problems in complex subtraction arithmetic. This study used small, intermediate and large split sizes, with each split condition being further divided into problems requiring and not requiring borrowing. The reaction times (RTs) for large and intermediate splits were significantly shorter than those for small splits, while accuracy was significantly higher for large and middle splits than for small splits, reflecting no speed–accuracy trade‐off. Further, RTs and accuracy differed significantly between the borrow and no‐borrow conditions only for small splits. This study indicates that strategy choice theory is suitable to explain the split effect in complex subtraction arithmetic. That is, individuals tend to choose the plausibility‐checking strategy or the whole‐calculation strategy according to the split size.
Testing a model of codependency for college students in Taiwan based on Bowen's concept of differentiation
Authors: Chang Shih‐Hua
Published: April 2016

The purpose of this study was to test a model of codependency based on Bowen's concept of differentiation for college students in Taiwan. The relations between family‐of‐origin dysfunction, differentiation of self, codependency traits and related symptoms including low self‐esteem, relationship distress and psychological adjustment problems were examined. Data were collected from 567 college students from 2 large, urban universities in northern Taiwan. Results indicated a significantly negative relationship between levels of codependency and self‐differentiation and that self‐differentiation partially mediated the relationship between family‐of‐origin dysfunction and codependency. The implications of these findings for counselling Taiwanese college students who experience codependency traits and related symptoms as well as suggestions for future research are discussed.
A comparison of preference‐assessment methods
Authors: Verriden Amanda L. , Roscoe Eileen M.
Published: April 2016

In Study 1, we evaluated preference stability across 4 preference‐assessment methods for 6 individuals, 5 of whom had autism spectrum disorder and 1 of whom had traumatic brain injury. We also measured participants’ problem behavior as a corollary measure during all assessment methods. The highest mean correlation coefficients and Kendall rank coefficients of concordance across administrations were observed for the paired‐stimulus and multiple‐stimulus‐without‐replacement methods. Lower correspondence across administrations was observed for the free‐operant and response‐restriction methods. Although differentially higher levels of problem behavior did not occur with a single method, lower levels were consistently observed with the free‐operant method. During Study 2, we evaluated the implications of lower coefficients on reinforcer efficacy by comparing an initially identified and an immediately identified high‐preference stimulus in a reinforcer assessment. Initially identified and immediately identified high‐preference stimuli were equally effective reinforcers, suggesting that fluctuations in preference do not necessarily affect reinforcer efficacy in practice.
In Search of the Transmission Mechanism of Fiscal Policy in the Euro Area
Authors: Fève Patrick , Sahuc Jean‐Guillaume
Published: April 2016

This paper applies the DSGE‐VAR methodology to assess the size of fiscal multipliers in the data and the relative contributions of two transmission mechanisms of government spending shocks, namely hand‐to‐mouth consumers and Edgeworth complementarity. Econometric experiments show that a DSGE model with Edgeworth complementarity is a better representation of the transmission mechanism of fiscal policy as it yields dynamic responses close to those obtained with the flexible DSGE‐VAR model (i.e. an impact output multiplier larger than one and a crowding‐in of private consumption). The estimated share of hand‐to‐mouth consumers is too small to replicate the positive response of private consumption. Copyright © 2016 John Wiley & Sons, Ltd.
DMSO‐ and Serum‐Free Cryopreservation of Wharton's Jelly Tissue Isolated From Human Umbilical Cord
Authors: Shivakumar Sharath Belame , Bharti Dinesh , Subbarao Raghavendra Baregundi , Jang Si‐Jung , Park Ji‐Sung , Ullah Imran , Park Ji‐Kwon , Byun June‐Ho , Park Bong‐Wook , Rho Gyu‐Jin
Published: April 2016

The facile nature of mesenchymal stem cell (MSC) acquisition in relatively large numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide (DMSO) for future use impedes its clinical utility. In this study, we compared the effect of two different cryoprotectants (DMSO and cocktail solution) on post‐thaw cell behavior upon freezing of WJ tissue following two different freezing protocols (Conventional [−1°C/min] and programmed). The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO. Post‐thaw growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in conjunction with programmed method (Prog‐Cock) were comparable with WJMSCs from fresh WJ tissue. They preserved their expression of surface markers, pluripotent factors, and successfully differentiated in vitro into osteocytes, adipocytes, chondrocytes, and hepatocytes. They also produced lesser annexin‐V‐positive cells compared to cells from WJ tissue stored using cocktail solution in conjunction with the conventional method (Conv‐Cock). Real‐time PCR and Western blot analysis of post‐thaw WJMSCs from Conv‐Cock group showed significantly increased expression of pro‐apoptotic factors (BAX, p53, and p21) and reduced expression of anti‐apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog‐Cock group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail solution in conjunction with programmed freezing method allows for an efficient WJ tissue banking for future MSC‐based regenerative therapies. J. Cell. Biochem. 117: 2397–2412, 2016. © 2016 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.
Molecular Dynamics Simulations of Ligand‐Induced Flap Conformational Changes in Cathepsin‐D—A Comparative Study
Authors: Arodola Olayide A. , Soliman Mahmoud E.S.
Published: April 2016

The flap region in aspartic proteases is a unique structural feature to this class of enzymes, and found to have a profound impact on protein overall structure, function, and dynamics. Understanding the structure and dynamic behavior of the flap regions is crucial in the design of selective inhibitors against aspartic proteases. Cathepsin‐D, an aspartic protease enzyme, has been implicated in a long list of degenerative diseases as well as breast cancer progression. Presented herein, for the first time, is a comprehensive description of the conformational flap dynamics of cathepsin‐D using a comparative 50 ns “multiple” molecular dynamics simulations. Diverse collective metrics were proposed to accurately define flap dynamics. These are distance d1 between the flap tips residues (Gly79 and Met301); dihedral angle ϕ; in addition to TriCα angles Gly79‐Asp33‐Asp223, θ1, and Gly79‐Asp223‐Met301, θ2. The maximum distance attained throughout the simulation was 17.42 and 11.47 Å for apo and bound cathepsin‐D, respectively, while the minimum distance observed was 8.75 and 6.32 Å for apo and bound cathepsin‐D, respectively. The movement of the flap as well as the twist of the active pocket can properly be explained by measuring the angle, θ1, between Gly79‐Asp33‐Met301 and correlating it with the distance Cα of the flap tip residues. The asymmetrical opening of the binding cavity was best described by the large shift of −6.26° to +20.94° in the dihedral angle, ϕ, corresponding to the full opening of the flap at a range of 31–33 ns. A wide‐range of post‐dynamic analyses was also applied in this report to supplement our findings. We believe that this report would augment current efforts in designing potent structure‐based inhibitors against cathepsin‐D in the treatment of breast cancer and other degenerative diseases. J. Cell. Biochem. 117: 2643–2657, 2016. © 2016 Wiley Periodicals, Inc.
Effect of Combined Action of Extracellular ATP and Elevated Calcium on Osteogenic Differentiation of Primary Cultures From Rat Calvaria
Authors: Laiuppa Juan A. , Santillán Graciela E.
Published: April 2016

The in vitro osteogenic differentiation has been intensively studied. However, it is not yet clear precisely how osteogenesis can be optimized. Changes in extracellular Ca2+ concentration ([Ca2+]e), as well as modulation of purinergic receptors play an important role in the regulation of osteoblasts differentiation and bone formation. In this study, we investigated the effects of a combined treatment of ATPγ‐S and high [Ca2+]e (5.35 mM) on osteogenic differentiation and function of primary cell cultures from rat calvaria. Our results indicate that ATPγ‐S stimulates cell transition from the G0 to S phase of cell cycle, involving the PI3K signaling pathway. Treatment with 10 or 100 µM ATPγ‐S and [Ca2+]e (ATP‐[Ca2+]e) for 48 h increases cell number significantly above the control. ATPγ‐S treatment in osteogenic medium containing [Ca2+]e stimulates the gene expression of BMP‐4, BMP‐5, and OPN at 16, 48, and 72 h, respectively, above control. In same conditions, treatment for 6 days with 10 µM UTP or 100 µM UDP significantly increased the ALP activity respect to control. Cells grown in osteogenic medium showed a statistically significant increase in calcium deposits at 15 and 18 days, for 10 µM ATPγ‐S treatment, and at 18 and 22 days, for [Ca2+]e treatment, respect to control but ATP‐[Ca2+]e treatment shown a significant greater mineralization at 15 days respect to ATPγ‐S, and at 18 days respect to both agonists. In conclusion, we demonstrated that an osteogenic medium containing 10 µM ATPγ‐S and 5.35 mM [Ca2+]e enhance osteogenesis and mineralization by rat primary calvarial cells cultures. J. Cell. Biochem. 117: 2658–2668, 2016. © 2016 Wiley Periodicals, Inc.
Impact of Braun anastomosis on reducing delayed gastric emptying following pancreaticoduodenectomy: a prospective, randomized controlled trial
Authors: Hwang Ho Kyoung , Lee Sung Hwan , Han Dai Hoon , Choi Sung Hoon , Kang Chang Moo , Lee Woo Jung
Published: April 2016

Background

The present study investigates the clinical impact of Braun anastomosis on delayed gastric emptying (DGE) after pylorus‐preserving pancreaticoduodenectomy (PPPD).

Methods

From February 2013 to June 2014, 60 patients were recruited for this randomized controlled trial. The incidence of DGE and its risk factors were analyzed according to whether or not Braun anastomosis was used after PPPD.

Results

Thirty patients were respectively enrolled in No‐Braun group and Braun group. A comparative analysis between the two groups showed no differences in sex, diagnosis, operation time, hospital stay, or postoperative complications, including pancreatic fistula. Overall DGE developed in eight patients (26.7%) in the Braun group and in 14 patients (46.7%) in the No‐Braun group (P = 0.108). However, clinically relevant DGE (grades B and C) was marginally more frequent in the No‐Braun group (23.3% vs. 3.3%, P = 0.052). In a multivariable analysis, No‐Braun anastomosis was an independent risk factor for developing clinically relevant DGE (odds ratio = 16.489; 95% confidence interval: 1.287–211.195; P = 0.031).

Conclusion

The overall DGE occurrence was not different between the two groups. However, No‐Braun anastomosis was an independent risk factor for developing clinically relevant DGE.
Influence of body habitus on feasibility and outcome of laparoscopic liver resections: a prospective study
Authors: Ratti Francesca , D'Alessandro Valentina , Cipriani Federica , Giannone Fabio , Catena Marco , Aldrighetti Luca
Published: April 2016

Background

The aim of the present study was to prospectively investigate whether the anthropometric measures of A Body Shape Index (ABSI, taking into account waist circumference adjusted for height and weight) affects feasibility and outcome of laparoscopic liver resections.

Methods

One hundred patients undergoing laparoscopic liver resection were prospectively included in the study (2014–2015). Preoperative clinical parameters, including body mass index (BMI) and ABSI were evaluated for associations with intraoperative outcome and postoperative results (morbidity, mortality and functional recovery).

Results

Twenty‐two and 78 patients underwent major and minor hepatectomies, respectively. Conversion rate was 9%, mean blood loss was 210 ± 115 ml. Postoperative morbidity was 15% and mortality was nil. Mean length of stay was 4 days. When considering the entire series, ABSI was not associated with intra and postoperative outcome. After stratification of patients according to difficulty score, Pearson's correlation demonstrated an association between ABSI and intraoperative blood loss (P = 0.03) and time for functional recovery (P = 0.05) in patients undergoing resections with high score of difficulty.

Conclusion

Body habitus has an influence on outcome of laparoscopic liver resections with high degree of difficulty, while feasibility and outcome of low difficulty resections seem not to be affected by anthropometric measures.
Value of severe liver iron overload for assessing heart iron levels in thalassemia major patients
Authors: Chen Xiaodong , Zhang Hui , Yang Qihua , Luo Zebin , Zhang Zuoquan , Cheng Ziliang , Mao Jiaji , Chan Queenie , Xu Honggui , Liang Biling , Guo Hua
Published: April 2016

Purpose

The relationship between severe liver iron overload (LIO) and heart iron overload (HIO) in transfusion‐dependent patients with thalassemia major (TM) is uncertain. Whether severe LIO can serve as an index for assessing heart iron deposition has vital clinical significance. Therefore, our aim is to determine if a close relationship exists between severe LIO and HIO.

Materials and Methods

We examined 110 TM patients who underwent T2* measurement in the liver and heart on a 1.5 Tesla MRI scanner. Various statistical analysis methods were used to assess the relationship.

Results

Most of these patients suffered from severe LIO (58.18%, liver T2* < 1.4 ms). Both Pearson's and Spearman's tests showed a significant correlation between liver T2* and heart T2* values (with a correlation coefficient of 0.408 and 0.550, respectively, both P < 0.0001). A nonlinear model, with the equation of Heart T2* = 37.974–17.684 / Liver T2*, was found to be the best model to indicate the relationship between liver T2* and heart T2*. Receiver operating characteristic (ROC) analysis showed the area under the ROC curve of liver T2* and serum ferritin for predicting HIO was 0.812 (95% confidence interval [CI]: 0.731–0.892; P < 0.0001) and 0.69 (95% CI: 0.585–0.795; P = 0.001), respectively.

Conclusion

Our preliminary data suggest the existence of a close relationship between severe LIO and HIO. High liver iron levels appear to increase the risk of heart iron deposition. This further supports the concept of critical liver iron concentration, above which elevated heart iron is present. J. MAGN. RESON. IMAGING 2016;44:880–889.