bluuebunny/crossref_metadata_2025 huggingface dataset:
Pd‐Catalyzed Hydrogen‐Transfer Reactions from Alcohols to C=C, C=O, and C=N Bonds
Authors: Muzart Jacques
Published: June 2015

This review covers Pd‐catalyzed abstracting and borrowing hydrogen transfers from alcohols to C=C, C=O, and C=N bonds. An abstracting hydrogen transfer implies a reaction in which an alcohol serves only as a hydrogen atom source, whereas in a borrowing hydrogen transfer the alcohol is part of the final product. Both transfer types involve a palladium monohydride or palladium dihydride, and are implicated in a variety of useful and safe one‐pot reactions such as the formation, with low quantities of waste material, of C–C, C–O, and C–N bonds. Plausible mechanisms are, as far as possible, provided.
A One‐Pot Synthesis of Triazolodiazepines
Authors: Hooyberghs Geert , Van Hove Sofie , Jacobs Jeroen , Van Meervelt Luc , Van der Eycken Erik V.
Published: June 2015

A one‐pot sequential A3‐coupling‐azidation‐cyclisation approach leading to potentially biologically active diazepine analogues has been developed. The implementation of the A3‐coupling reaction ensures diversity. Attention is given to this so far rarely studied structural motif of fused heterocyclic diazepines.
Prisms for pain. Can visuo‐motor rehabilitation strategies alleviate chronic pain?
Authors: Torta D.M. , Legrain V. , Rossetti Y. , Mouraux A.
Published: June 2015

Background and aims

Prism adaptation (PA) is a non‐invasive procedure in which participants perform a visuo‐motor pointing task while wearing prism goggles inducing a lateral displacement of the visual field and a mismatch between the seen and felt position of the pointing hand. PA is thought to induce a reorganization of sensorimotor coordination, and has been used successfully to rehabilitate neglect following right‐hemisphere lesions. Because studies have shown that complex regional pain syndrome (CRPS) is associated with neglect‐like symptoms, it was proposed that PA could be used to alleviate pain in these patients.

Database

A search for peer‐reviewed articles on neglect‐like symptoms in CRPS and on the use of prisms in CRPS was conducted using the PubMed database.

Results

There is still no agreement as to whether CRPS patients really present neglect symptoms and, if they do, what it is that they neglect. Furthermore, there is insufficient data to determine whether PA exerts an effect on CRPS symptoms. Finally, it remains unknown whether neglect can be observed in other types of lateralized pain, or whether PA could be useful for these patients.

Conclusion

By highlighting open issues, our review provides guidelines for future studies on the use of prisms in pain. The assessment of neglect in patients with CRPS as well as other types of lateralized chronic pain should be characterized using a combination of neuropsychological methods assessing the multiple aspects of neglect in a more refined manner. In addition, further studies should investigate the mechanisms through which PA may modulate pain.
I need you closer to me: Effects of affiliation goals on perceptions of interpersonal distance
Authors: Stel Mariëlle , van Koningsbruggen Guido M.
Published: June 2015

People's perceptions are often distorted in a way that aligns with their desires and goals. We argue that having a goal to affiliate changes the perception of interpersonal distance in a way that may help to fulfil this affiliation goal. As other people are goal‐relevant when having an affiliation goal, we expected that people with affiliation goals would estimate the distance between themselves and another person as smaller than people with no affiliation goals. In two studies, we manipulated affiliation goals by priming participants with affiliation or control words. Our main dependent variable was the estimated interpersonal distance between themselves and the experimenter. Results showed that participants primed with affiliation estimated the interpersonal distance as smaller compared with participants primed with control words. We did not obtain reliable differences between the affiliation and control conditions on other distance and height estimations. Our results suggest that having or not having affiliation goals influences people's perception of the distance between them and other people.
Enhancing detection coverage in untargeted metabolomics analysis by solid‐phase extraction on‐line coupled to LC–MS/MS
Authors: Calderón‐Santiago Mónica , Priego‐Capote Feliciano , de Castro María D. Luque
Published: June 2015

One of the main limitations of untargeted metabolomics analysis is the low detection coverage of analytical techniques such as NMR, LC–MS, or GC–MS. In this research, the detection coverage of an automated approach configured by the on‐line coupling of SPE to LC–MS/MS was evaluated by combination of sorbents based on different retention mechanisms. The approach was applied to the analysis of human serum using three types of sorbents: alkyl bonded silica, polymeric resins, and mixed‐mode ionic resins. The combination of four sorbents (C18, a modified polystyrene–divinylbenzene resin and two mixed‐mode ionic resins) led to the best extraction results and, therefore, the best detection coverage, which is explained by their complementary retention mechanisms. However, some of the sorbents provide a high detection coverage by themselves, as is the case with C18, which can afford to retain almost 83% of all detected entities. Taking into account the complementarity between pairs of these sorbents (C18 and the polystyrene–divinylbenzene resin with the mixed‐mode ionic resins), dual cartridge SPE–LC–MS/MS configurations were designed for serum analysis. These configurations allowed increasing the detection coverage up to 91% of the total number of molecular features detected with all sorbents tested. An additional benefit of the SPE–LC–MS/MS strategy was the improvement of sensitivity as compared to protein precipitation and fractionation with methanol and chloroform. Thus, an average preconcentration factor of 10–75 was obtained in the SPE‐based approach versus the two‐phase protocol for metabolites extraction.
Assessment of accumulation rates in small reservoirs by core analysis, 137Cs measurements and bathymetric mapping in Burkina Faso
Authors: Schmengler Almut C. , Vlek Paul L.G.
Published: June 2015

Reservoir siltation is one of the most important off‐site effects of soil erosion. In Burkina Faso a large number of small dams have been built to store rainfall and runoff water in the rainy season, which is much needed for domestic use, irrigation and stock watering in the dry season. This study quantifies the siltation rates of two small reservoirs in southwestern Burkina Faso by comparing the initial and current reservoir bed morphology and by analyzing variations in accumulated sediment in terms of stratigraphical changes and 137Cs concentrations. Results of a bathymetric survey show that both reservoirs have already lost approximately 10% to 15% of their original storage capacity at normal pool level and more than 60% of their initial inactive storage volume at spillway level in the last 15 to 20 years. During this period, inflow sediment had accumulated on the bottom of the reservoir to a thickness of 0.3 m to 0.5 m. Sediment core measurements confirmed this thickness by showing a clear stratigraphical change in core properties with significant variations in the 137Cs concentrations at these specific depths. The thickness of accumulated sediment on top of the relict soil indicates that the reservoirs have a ‘half‐life’ of about 40 to 45 years before siltation might affect its water supply and flood control. Compared with other reservoir studies in West Africa these siltation rates can be seen as reasonable but not alarmingly high. Nevertheless, many of the small dams built during the 1980s are likely to reach their ‘half‐life’ in about 10 to 20 years causing hydrological and geomorphological changes upstream and downstream of the dams. Therefore, further research studies should focus on prevention measures to reduce the off‐site effects of erosion and thus to slow down the process of siltation. Copyright © 2015 John Wiley & Sons, Ltd.
Influence of in ovo mercury exposure, lake acidity, and other factors on common loon egg and chick quality in Wisconsin
Authors: Kenow Kevin P. , Meyer Michael W. , Rossmann Ronald , Gray Brian R. , Arts Michael T.
Published: June 2015

A field study was conducted in Wisconsin (USA) to characterize in ovo mercury (Hg) exposure in common loons (Gavia immer). Total Hg mass fractions ranged from 0.17 µg/g to 1.23 µg/g wet weight in eggs collected from nests on lakes representing a wide range of pH (5.0–8.1) and were modeled as a function of maternal loon Hg exposure and egg laying order. Blood total Hg mass fractions in a sample of loon chicks ranged from 0.84 µg/g to 3.86 µg/g wet weight at hatch. Factors other than mercury exposure that may have persistent consequences on development of chicks from eggs collected on low-pH lakes (i.e., egg selenium, calcium, and fatty acid mass fractions) do not seem to be contributing to reported differences in loon chick quality as a function of lake pH. However, it was observed that adult male loons holding territories on neutral-pH lakes were larger on average than those occupying territories on low-pH lakes. Differences in adult body size of common loons holding territories on neutral-versus low-pH lakes may have genetic implications for differences in lake-source-related quality (i.e., size) in chicks. The tendency for high in ovo Hg exposure and smaller adult male size to co-occur in low-pH lakes complicates the interpretation of the relative contributions of each to resulting chick quality. Environ Toxicol Chem 2015;34:1870–1880. © 2015 SETAC
Bioaccumulation, subcellular distribution, and acute effects of chromium in Japanese medaka (Oryzias latipes)
Authors: Li Lixia , Chen Hongxing , Bi Ran , Xie Lingtian
Published: June 2015

Chromium (Cr) is an essential element but is toxic to aquatic organisms at elevated concentrations. In the present study, adult Japanese medaka (Oryzias latipes) were exposed to a sublethal hexavalent chromium (Cr(VI)) concentration via dissolved and dietary exposures for 6 d. Various measurements of Cr were made: bioaccumulation in different tissues, subcellular distribution in the liver, effects on antioxidants and acetylcholinesterase (AChE), and Cr-induced lipid peroxidation. The results showed that bioaccumulation increased dramatically in all tested tissues from dissolved exposure but only significantly in the intestine from dietary treatment, implying that dissolved exposure may be predominant for Cr accumulation in medaka. Subcellular distribution revealed that Cr accumulated in the liver was mainly (46%) associated with the heat-stable protein fraction. Among the antioxidants examined, catalase (CAT) responded to dissolved Cr exposure in most tissues whereas superoxide dismutase (SOD) was less responsive. Malondialdehyde concentrations were significantly elevated in most tissues examined in the dissolved Cr-exposed fish, but were only elevated in the liver and intestine in the dietary Cr-exposed fish. The AChE activity in the brain was stimulated by 49% in the dissolved Cr-exposed fish. Reductions in condition factor and gonadosomatic index were also observed. These data help in an understanding of Cr tissue distribution and the acute effects of Cr in Japanese medaka. Environ Toxicol Chem 2015;34:2611–2617. © 2015 SETAC
Social Space and Field as Constructs for Evaluating Social Inclusion
Authors: Lapidot‐Lefler Noam , Friedman Victor J. , Arieli Daniella , Haj Noha , Sykes Israel , Kais Nasreen
Published: June 2015

This paper addresses the role of evaluation in promoting social inclusion, an important component of social justice, with a focus on exclusion resulting from physical disability. We argue that the evaluation of social exclusion and social inclusion requires evaluators not only to reconsider their role and methods, but also to revise the fundamental constructs through which they study how programs and other interventions generate change at the individual, group, community, and societal levels. Drawing on field theory, we suggest that social inclusion processes can be understood and assessed in terms of the expansion of individuals’ life space, which consists of social, political, cultural, and resource dimensions. The paper illustrates these constructs with data from a participative action evaluation of a pilot program for providing services to people with disabilities in Israel. Our aim in developing these constructs is to provide not only tools for assessment, but also ways of thinking that may enable socially excluded people to be more active agents of inclusion.
Social Justice in Action: The Contribution of Evaluation to Employment Integration of a Vulnerable Population—The Case of College Graduates With Learning Disabilities
Authors: Desivilya Syna Helena , Rottman Amit , Raz Michal
Published: June 2015

This article presents and discusses an evaluation model that can contribute to social justice and that increases equal opportunities of employment for a vulnerable population—college graduates with learning disabilities. The framework responds to increasingly competitive job markets’ potential exclusion of vulnerable social groups from meaningful participation in this domain, consequently impeding social justice. Counteracting socioeconomic gaps in societies requires active involvement of community members, social institutions, and government. According to the proposed model, the evaluator assumes such an active stance by building genuine partnership with evaluees. We present the sociopolitical and socioeconomic context—the “brave” new job market foreshadowing the evaluation and social justice interface. The model is illustrated through a case study—evaluation of an innovative program supporting the transition of learning disabled college graduates to the job market.
Evaluation in the Branco Weiss Institute: From Social Vision to Educational Practice
Authors: Lustig Ruthie , Ben Baruch‐Koskas Shira , Makhani‐Belkin Tova , Hirsch Tami
Published: June 2015

This article presents the unique development of the evaluation unit at the Branco Weiss Institute (BWI) in Jerusalem, an educational nongovernmental organization designed to enhance individual and social growth and to reduce educational gaps in Israeli society. The Institute, which operates a network of schools for at‐risk students along with comprehensive high schools, develops and implements educational and social programs in Israel's social and geographic periphery. The article describes the evaluation unit at the Institute as a democratic and culturally responsive mechanism that promotes social justice through the participation of all stakeholders in an ongoing dialogue that generates new knowledge for the organization and its programs. The article includes an illustration of the implementation of the model in a school program for pupils of Ethiopian origin.
Evaluation of a Joint Israeli–Palestinian Project
Authors: Steinberg Shoshana , Zamir Judith
Published: June 2015

This article presents three examples of evaluation intervention demonstrating the ongoing significance of a politically responsive approach. The article's main goal is to shed light on the evaluator's role, through the work of a mixed team of Israeli and Palestinian teachers, within a conflict, in an uncomfortable zone context. Israeli and Palestinian teachers participated in a project aimed at producing a history textbook including the narratives of each group, each of whom had its own legitimate objectives. This article intends to highlight the significant contribution of the evaluator to the entire process through the use of three different evaluation tools.
Problems correlating the late Brigantian–Arnsbergian Western European substages within northern England
Authors: Cózar P. , Somerville I. D.
Published: June 2015

A detailed study of foraminiferal assemblages recorded in limestones from northern England in the Stainmore Trough and Alston Block permits their assignment to different European substages than in previous studies. Comparisons with foraminiferal assemblages, mostly from Russia, allow the biozonations to be correlated with the Viséan, Serpukhovian and Bashkirian international stages, as well as with the Russian (and Ukrainian) substages for the Serpukhovian (Tarussian, Steshevian, Protvian and Zapaltyubian). The Scar Limestone and Five Yard Limestone Members are assigned to the Tarussian and, thus, represent the lowermost part of the formal Serpukhovian Stage. This new correlation coincides closely with the first occurrence of the conodontLochriea zieglerifrom levels equivalent to the Single Post Limestone that could potentially form the revised base for the Serpukhovian. The Three Yard Limestone Member is correlated with the base of the Steshevian substage which also includes the Four Fathom Limestone Member, Great Limestone Member and Little Limestone. The base of the Protvian is considered to lie within the Crag Limestone, whereas the Rookhope Shell Band contains foraminiferal assemblages more typical of the Zapaltyubian in the Ukraine and Chernyshevkian in the Urals. Assemblages of the Upper Fell Top Limestone and Grindstone/Botany Limestones contain foraminiferal species that have been used for the recognition of the Bashkirian elsewhere. There is no other fossil group which allows the calibration of those foraminiferal assemblages, because ammonoids are virtually absent in the shallow‐water cyclothemic successions and conodonts have not been studied in detail in this region. The Mid‐Carboniferous boundary and the Voznessenian substage might be reasonably located below the Upper Fell Top Limestone. Copyright © 2015 John Wiley & Sons, Ltd.
NTU‐DSI‐122: A diffusion spectrum imaging template with high anatomical matching to the ICBM‐152 space
Authors: Hsu Yung‐Chin , Lo Yu‐Chun , Chen Yu‐Jen , Wedeen Van Jay , Isaac Tseng Wen‐Yih
Published: June 2015

A diffusion‐weighted (DW) template in a standard coordinate system is often necessary for the analysis of white matter (WM) structures using DW images. Although several DW templates have been constructed in the ICBM‐152 space, a template for diffusion spectrum imaging (DSI) is still lacking. In this study, we developed a DSI template in the ICBM‐152 space from 122 healthy adults. This high quality template, NTU‐DSI‐122, was built through incorporating the macroscopic anatomical information using high‐resolution T1‐weighted images and the microscopic structural information obtained from DSI datasets. Two evaluations were conducted to examine the quality of NTU‐DSI‐122. The first evaluation examined the anatomical consistency of NTU‐DSI‐122 in matching to the ICBM‐152 coordinate system. The results showed that this template matched to the ICBM‐152 templates very well across the whole brain, not only in the deep white matter regions as other DW templates but also in the superficial white matter regions. In the second evaluation, a large number of independent diffusion tensor imaging (DTI) datasets were registered to the DTI template derived from NTU‐DSI‐122. The examination was performed by quantifying the anatomical consistency among the registered DTI datasets. The results showed that using NTU‐DSI‐122 as the registration template the registered DTI datasets can achieve high anatomical alignment. Both evaluations demonstrate that NTU‐DSI‐122 is a useful high quality DW template. Therefore, NTU‐DSI‐122 can serve as a representative DSI dataset for a healthy adult population, and will be of potential value for brain research and clinical applications. The NTU‐DSI‐122 template is available at http://www.nitrc.org/projects/ntu‐dsi‐122/. Hum Brain Mapp 36:3528–3541, 2015. © 2015 Wiley Periodicals, Inc.
Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample
Authors: Yang Xu , Tang Xiao‐peng , Zhang Yong‐hong , Luo Kai‐zhong , Jiang Yong‐fang , Luo Hong‐yu , Lei Jian‐hua , Wang Wen‐long , Li Ming‐ming , Chen Han‐chun , Deng Shi‐lin , Lai Li‐ying , Liang Jun , Zhang Min , Tian Yi , Xu Yun
Published: June 2015

Hepatic copper determination is an important test for the diagnosis of Wilson's disease (WD). However, the method has not been standardized, the diagnostic accuracy has not been evaluated prospectively, and the optimal cut‐off value remains controversial. Accordingly, we aimed to prospectively evaluate the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Patients for whom a liver biopsy was indicated were consecutively enrolled. Hepatic copper content was determined with atomic absorption spectroscopy. All assays were performed using careful quality control by a single technician. WD diagnosis was based on WD score or its combination with clinical follow‐up results. A total of 3,350 consecutive patients underwent liver biopsy. Six hundred ninety‐one patients, including 178 with WD, underwent two passes of liver biopsy with hepatic copper determination. Mean hepatic content in WD patients was 770.6 ± 393.2 μg/g dry weight (wt). Sensitivity, specificity, and positive and negative predictive values of hepatic copper content for WD diagnosis in the absence of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis at the cut‐off value of 250 μg/g dry wt. were 94.4%, 96.8%, 91.8%, and 97.8%, respectively. The most useful cut‐off value was 209 μg/g dry wt, with a sensitivity and specificity of 99.4% and 96.1%, respectively. A total of 23.3% of patients without WD and PBC had hepatic copper content >75 μg/g dry wt. Conclusion: A liver biopsy sample of more than 1 mg dry wt may reliably reflect hepatic copper content and should be used for hepatic copper determination. Hepatic copper determination is a very valid procedure for the diagnosis of WD, and the most useful cut‐off value is 209 μg/g dry wt.(Hepatology 2015;62:1731–1741)
Hepatitis C virus drug resistance–associated substitutions: State of the art summary
Authors: Lontok Erik , Harrington Patrick , Howe Anita , Kieffer Tara , Lennerstrand Johan , Lenz Oliver , McPhee Fiona , Mo Hongmei , Parkin Neil , Pilot‐Matias Tami , Miller Veronica
Published: June 2015

Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon‐free, all‐oral combinations of direct‐acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct‐acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials. Conclusion: This report provides a comprehensive, systematic review of all resistance information available from sponsors’ trials as a tool to inform the HCV drug development field. (Hepatology 2015;62:1623–1632)
Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid‐like nanoparticles resolves liver fibrosis
Authors: Jiménez Calvente Carolina , Sehgal Alfica , Popov Yury , Kim Yong Ook , Zevallos Victor , Sahin Ugur , Diken Mustafa , Schuppan Detlef
Published: June 2015

Fibrosis accompanies the wound‐healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I. Fibrosis often progresses to cirrhosis. Here we present in vivo evidence of an up to 90% suppression of procollagen α1(I) expression, a reduction of septa formation, and a 40%‐60% decrease of collagen deposition in mice with progressive and advanced liver fibrosis that received cationic lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene. After intravenous injection, up to 90% of lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene were retained in the liver of fibrotic mice and accumulated in nonparenchymal more than parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis. Conclusion: Our lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene specifically reduce total hepatic collagen content without detectable side effects, potentially qualifying as a therapy for fibrotic liver diseases. (Hepatology 2015;62:1285‐1297)
Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis
Authors: Aqel Bashar A. , Pungpapong Surakit , Leise Michael , Werner K. Tuesday , Chervenak Amy E. , Watt Kymberly D. , Murphy Jennifer L. , Ryland Kristen , Keaveny Andrew P. , McLemore Ryan , Vargas Hugo E.
Published: June 2015

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (Hepatology 2015;62:1004‐1012)
Circulating tumor cells are associated with poor overall survival in patients with cholangiocarcinoma
Authors: Yang Ju Dong , Campion Michael B. , Liu Minetta C. , Chaiteerakij Roongruedee , Giama Nasra H. , Ahmed Mohammed Hager , Zhang Xiaodan , Hu Chunling , Campion Victoria L. , Jen Jin , Venkatesh Sudhakar K. , Halling Kevin C. , Kipp Benjamin R. , Roberts Lewis R.
Published: June 2015

Circulating tumor cells (CTCs) in blood are associated with poor survival of patients with breast, prostate, or colon cancer. We hypothesized that CTCs are associated with poor survival of patients with cholangiocarcinoma (CCA). Eighty‐eight patients with CCA were prospectively enrolled at Mayo Clinic Rochester between June 2010 and September 2014. The CellSearch system by Veridex was used for detection of CTCs in peripheral blood. Associations between CTC, patient and tumor characteristics, and survival were examined using the Cox's proportional hazards model. Fifteen patients (17%) were positive for CTC ≥2 and 8 patients (9%) for CTC ≥5. CTCs were associated with tumor extent. CTC ≥2 (hazard ratio [HR]: 2.5; 95% confidence interval [CI]: 1.1‐5.4; P = 0.02) and CTC ≥5 (HR, 4.1; 95% CI: 1.4‐10.8; P = 0.01) were both independent predictors of survival. In subgroup analyses, CTC ≥2 (HR, 8.2; 95% CI: 1.8‐57.5; P < 0.01) and CTC ≥5 (HR, 7.7; 95% CI: 1.4‐42.9; P = 0.02) were both associated with shorter survival among patients with metastasis. There was a trend toward association of CTC ≥5 with shorter survival in patients with nonmetastatic CCA (HR, 4.3; 95% CI: 1.0‐13.8; P = 0.06). CTC ≥2 (HR, 10.5; 95% CI: 2.2‐40.1; P < 0.01) and CTC ≥5 (HR, 10.2; 95% CI: 1.5‐42.3; P = 0.02) were both associated with shorter survival among patients with perihilar/distal CCA. CTC ≥5 was associated with shorter survival of patients with intrahepatic CCA (HR, 4.2; 95% CI: 1.1‐14.1; P = 0.04). Conclusion: CTCs were associated with more‐aggressive tumor characteristics and independently associated with survival in patients with CCA. Assessment of CTCs may be useful for identifying CCA patients at risk of early mortality. (Hepatology 2016;63:148–158)
Effects of Pre‐annealing on Firing Stability of Atomic Layer‐Deposited Al2O3
Authors: Bae Soohyun , Kim Soo Min , Lee Kyung Dong , Kim Young Do , Park Sungeun , Kang Yoonmook , Lee Hae‐Seok , Kim Donghwan
Published: June 2015

Al2O3 layers fabricated with atomic layer deposition (ALD) show high levels of surface passivation on p‐ and n‐type silicon wafers. In order to form front and rear electrodes, Al2O3 layers should undergo a firing process at a high peak temperature. Therefore, the Al2O3 layer must be stable under these conditions to maintain a high level of surface passivation during the firing process. In this study, Al2O3 layers fabricated with ALD were pre‐annealed to enhance their thermal stability during the firing process. From quasi‐steady state photoconductance (QSSPC) measurements, the difference between the implied Voc values of the pre‐annealed and fired samples was found to be smallest (3 mV) when the sample was pre‐annealed at 620 °C. The surface recombination rate calculated from capacitance‐voltage (C‐V) measurements of metal‐Al2O3‐Si (metal‐insulator‐semiconductor) structures was shown to be low when the sample was pre‐annealed at 600–650 °C. Thus, firing stability was achieved with pre‐annealing at 620 °C by reducing the surface recombination rate. We conclude that it is necessary to pre‐anneal the Al2O3 passivation layer at this specific temperature to reduce the degradation of the passivation quality of Al2O3 after the firing process.
Of Rather Than in a Place
Authors: Davis Carol Ann
Published: June 2015

This commentary describes the formation of the Newtown Poetry Project and its relationship to other literacy activities that Davis has performed over the last decade.
Hepatotoxicity mechanisms of isoniazid: A mini‐review
Authors: Hassan Hozeifa M. , Guo Hong‐li , Yousef Bashir A. , Luyong Zhang , Zhenzhou Jiang
Published: June 2015

Isoniazid (INH) is an antituberculosis drug associated with idiosyncratic liver injury in susceptible patients. INH‐induced hepatotoxicity remains a significant clinical problem, but the underlying mechanisms are still unclear, despite the growing evidence that INH and/or its major metabolite, hydrazine, play an important role in hepatotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.
Complement C5a–C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice
Authors: Zhang Jia‐xiang , Zha Wan‐sheng , Ye Liang‐ping , Wang Feng , Wang Hui , Shen Tong , Wu Chang‐hao , Zhu Qi‐xing
Published: June 2015

We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi‐organ damage including the kidneys. In particular, excessive deposition of C5 and C5b‐9‐the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE‐sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up‐regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE‐induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro‐inflammatory cytokines IL‐2, TNF‐α and IFN‐γ in the kidney tissue (P < 0.05); this was accompanied by increased expression of P‐p38, P‐ERK and P‐JNK proteins (P < 0.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P‐p38, P‐ERK and P‐JNK proteins (P < 0.05) and also consistently reduced the TCE sensitization‐induced increase of IL‐2, TNF‐α and IFN‐γ (P < 0.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement‐mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright © 2015 John Wiley & Sons, Ltd.
Titanium and hydroxyapatite coating of polyetheretherketone and carbon fiber‐reinforced polyetheretherketone: A pilot study in sheep
Authors: Stübinger Stefan , Drechsler Anika , Bürki Alexander , Klein Karina , Kronen Peter , von Rechenberg Brigitte
Published: June 2015

Purpose: The purpose of this study was to evaluate the bone formation capability of polyetheretherketone (PEEK) and carbon fiber‐reinforced PEEK (CFR‐PEEK) implants coated with different titanium and hydroxyapatite plasma‐sprayed layers after 2 and 12 weeks. Methods: In six sheep 108 implants were placed in the pelvis. Altogether six different surface modifications were tested. After 2 and 12 weeks, n = 3 implants per group were examined histologically and n = 6 implants per group were tested by a pull‐out test. Results: Biomechanically (p = 0.001) as well as histologically (p > 0.05) surface coating of PEEK/CFR‐PEEK led to an increase of osseointegration from 2 to 12 weeks. After 12 weeks, coated implants demonstrated significant (p < 0.001) higher pull‐out values in comparison to uncoated implants. Overall, the double coating (titanium bond layer and hydroxyapatite top layer) showed the most favorable results after 2 and 12 weeks. Conclusions: Plasma‐sprayed titanium and hydroxyapatite coatings on PEEK or CFR‐PEEK demonstrated a significant improvement of osseointegration. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1182–1191, 2016.
Bone Geometry, Volumetric Density, Microarchitecture, and Estimated Bone Strength Assessed by HR-pQCT in Adult Patients With Type 1 Diabetes Mellitus
Authors: Shanbhogue Vikram V , Hansen Stinus , Frost Morten , Jørgensen Niklas Rye , Hermann Anne Pernille , Henriksen Jan Erik , Brixen Kim
Published: June 2015

The primary goal of this cross-sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD–, respectively) and to compare them with age-, gender-, and height-matched healthy control subjects (CoMVD+ and CoMVD–, respectively). The secondary goal was to assess differences in MVD– and MVD+ patients. Fifty-five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR-pQCT parameters between MVD– and CoMVD– subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD– patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD– groups in comparison to controls, they were similar between the MVD+ and MVD– groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients. © 2015 American Society for Bone and Mineral Research.
Crocin Prevents Patulin‐Induced Acute Toxicity in Cardiac Tissues via the Regulation of Oxidative Damage and Apoptosis
Authors: Boussabbeh Manel , Ben Salem Intidhar , Neffati Fadwa , Najjar Mohamed Fadhel , Bacha Hassen , Abid‐Essefi Salwa
Published: June 2015

Patulin (PAT) is a mycotoxin produced by several species of the genera of Penicillium, Aspergillus, and Byssochlamys principally by Penicillium expansum. This mycotoxin is suspected to affect several organs including kidney and liver. However, its toxic effect on heart remains unknown. The present study investigated for the first time the cardiotoxic effect of PAT in mice. We demonstrated that PAT increased creatinin phosphokinase (CPK) level, induced lipoperoxydation and protein oxidation, and triggered the antioxidant enzymes such as superoxide dismutase and catalase activities. We also demonstrated that acute administration of PAT triggers apoptosis via P53 overexpression and caspase 3 activation. We further investigated the antioxidant efficiency of crocin (CRO), a carotenoid pigment, against PAT‐induced cardiotoxicity. We found that pretreatment with CRO prevents cardiac impairment by reducing CPK levels, restoring the redox statute and suppressing apoptosis. Collectively, our data provide new preventive effect of CRO toward PAT‐induced cardiotoxicity in mice.
Heats of formation of platonic hydrocarbon cages by means of high‐level thermochemical procedures
Authors: Karton Amir , Schreiner Peter R. , Martin Jan M. L.
Published: June 2015

Hydrocarbon cages are key reference materials for the validation and parameterization of computationally cost‐effective procedures such as density functional theory (DFT), semiempirical molecular orbital theory, and molecular mechanics. We obtain accurate total atomization energies (TAEs) and heats of formation (ΔfH°298) for platonic and prismatic hydrocarbon cages by means of the Wn‐F12 explicitly correlated thermochemical protocols. We consider the following kinetically stable (CH)npolycyclic hydrocarbon cages: (i) platonic hydrocarbons (tetrahedrane, cubane, and dodecahedrane), (ii) prismatic hydrocarbons (triprismane, cubane, and pentaprismane), and (iii) one truncated tetrahedrane (octahedrane). Our best theoretical heat of formation for cubane (144.8 kcal mol−1) suggests that the experimental value adopted by the NIST thermochemical database (142.7 ± 1.2 kcal mol−1) should be revised upwards by ∼2 kcal mol−1. Our best heat of formation for dodecahedrane (20.2 kcal mol−1) suggests that the semiexperimental value (22.4 ± 1 kcal mol−1) should be revised downward by ∼2 kcal mol−1. We use our benchmark Wn‐F12 TAEs to evaluate the performance of a variety of computationally less demanding composite thermochemical procedures. These include the Gaussian‐n(Gn) and the complete basis set (CBS) methods. The CBS‐QB3 and CBS‐APNO procedures show relatively poor performance with root‐mean‐squared deviations (RMSDs) of 4.2 and 2.5 kcal mol−1, respectively. The best performers of the Gnprocedures are G4 and G3(MP2)B3 (RMSD = 0.5 and 0.6 kcal mol−1, respectively), while the worst performers are G3 and G4(MP2)‐6X (RMSD = 2.1 and 2.9 kcal mol−1, respectively). Isodesmic and even homodesmotic reactions involving these species are surprisingly challenging targets for DFT computations. © 2015 Wiley Periodicals, Inc.
Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy
Authors: De Arcangelis Valeria , Strimpakos Georgios , Gabanella Francesca , Corbi Nicoletta , Luvisetto Siro , Magrelli Armando , Onori Annalisa , Passananti Claudio , Pisani Cinzia , Rome Sophie , Severini Cinzia , Naro Fabio , Mattei Elisabetta , Di Certo Maria Grazia , Monaco Lucia
Published: June 2015

Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X‐linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray‐based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up‐regulation of PGC‐1α; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z‐disk. J. Cell. Physiol. 230: 224–232, 2016. © 2015 Wiley Periodicals, Inc.
Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells
Authors: He Bin , Zhang Nana , Zhao Ruqian
Published: June 2015

Synthetic glucocorticoids (GCs) such as dexamethasone (Dex) are widely given to pregnant women to induce maturation and improve viability of preterm infants. Despite the beneficial effects, synthetic GCs have adverse effects on placental growth and nutrient transport system. However, the molecular mechanisms involved in these events remain unknown. Here we use a human placental choriocarcinoma cell line (BeWo) as model to explore the pathway linking amino acids transport with cell viability under Dex challenge. BeWo cells treated with Dex (100 nM) for 24 h demonstrated G1/S cell cycle arrest together with enhanced autophagy and apoptosis. Concurrently, the amino acid carrier SLC7A5 was down‐regulated in association with impaired cellular amino acids uptake and inhibition of mammalian target of rapamycin (mTOR) signaling. Similar cellular responses were observed in BeWo cells treated with BCH, a classical System L inhibitor which inactivates SLC7A5. The glucocorticoid receptor (GR) antagonist RU486 was able to diminish Dex‐induced translocation of GR into nucleus and to abolish these effects. Furthermore, Dex treatment significantly promoted the binding of GR to the proximal promoter sequence of SLC7A5 gene. Taken together, our results show that Dex downregulates SLC7A5 expression via GR‐mediated transrepression. The impaired amino acids uptake leads to inhibition of mTOR signaling which in turn causes inhibited proliferation and enhanced autophagy and apoptosis in BeWo cells. These findings indicate that SLC7A5 mediates the effect of Dex on cell viability, thus providing a novel molecular target for the prevention and treatment of Dex‐induced cell cycle arrest and apoptosis in placental cells. J. Cell. Physiol. 230: 233–242, 2016. © 2015 Wiley Periodicals, Inc.
Multicenter comparative study of laparoscopic and open distal pancreatectomy using propensity score‐matching
Authors: Nakamura Masafumi , Wakabayashi Go , Miyasaka Yoshihiro , Tanaka Masao , Morikawa Takanori , Unno Michiaki , Tajima Hiroshi , Kumamoto Yusuke , Satoi Sohei , Kwon Masanori , Toyama Hirochika , Ku Yonson , Yoshitomi Hideyuki , Nara Satoshi , Shimada Kazuaki , Yokoyama Takahide , Miyagawa Shinichi , Toyama Yoichi , Yanaga Katsuhiko , Fujii Tsutomu , Kodera Yasuhiro ,   Study Group of JHBPS,   JSEPS, Tomiyama Yasuyuki , Miyata Hiroaki , Takahara Takeshi , Beppu Toru , Yamaue Hiroki , Miyazaki Masaru , Takada Tadahiro
Published: June 2015

Background

Laparoscopic distal pancreatectomy has been shown to be associated with favorable postoperative outcomes using meta‐analysis. However, there have been no randomized controlled studies yet. This study aimed to compare laparoscopic and open distal pancreatectomy using propensity score‐matching.

Methods

We retrospectively collected perioperative data of 2,266 patients who underwent distal pancreatectomy in 69 institutes from 2006–2013 in Japan. Among them, 2,010 patients were enrolled in this study and divided into two groups, laparoscopic distal pancreatectomy and open distal pancreatectomy. Perioperative outcomes were compared between the groups using unmatched and propensity matched analysis.

Results

After propensity score‐matching, laparoscopic distal pancreatectomy was associated with favorable perioperative outcomes compared with open distal pancreatectomy, including higher rate of preservation of spleen and splenic vessels (P < 0.001); lower rates of intraoperative transfusion (P = 0.020), clinical grade of pancreatic fistula (International Study Group on Pancreatic Fistula grade B and C; P < 0.001), and morbidity (P < 0.001); and shorter hospital stay (P = 0.001), but a longer operative time (P < 0.001).

Conclusions

Laparoscopic distal pancreatectomy was associated with more favorable perioperative outcomes than open distal pancreatectomy.
Synthesis of New 3‐(Furan‐2‐yl)‐Substituted Dibenzo‐Diazepin‐1‐one Derivatives
Authors: Wang Fang‐Ming , Bao Dan , Wang Ming , Yin Qing‐Huan , Chen Li‐Zhuang , Han Guang‐Fan
Published: June 2015

A new series of 3‐(furan‐2‐yl) dibenzo‐diazepin‐1‐one derivatives were synthesized by condensation of 5‐(furan‐2‐yl)‐1,3‐cyclohexanedione, o‐phenylenediamine, and aromatic aldehydes, in which in some of them existed two very close isomer compounds. All the compounds were characterized by IR, MS, 1H NMR, and elemental analysis. Also presented were the crystal structures of 3a, 3b and 3e, which were obtained and determined by X‐ray single‐crystal diffraction.