bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controllable design of nanostructure in block copolymer reinforced epoxy composites
Authors: Heng Zhengguang , Zhang Haoruo , Chen Yang , Zou Huawei , Liang Mei 
Published: February 2018

ABSTRACTThe modification of epoxy composites through the construction of nanostructures via the self‐organization of block copolymers in epoxy has become a hot topic. In this research, polystyrene‐b‐poly(ɛ‐caprolactone)‐b‐polydimethylsiloxane‐b‐poly(ɛ‐caprolactone)‐b‐polystyrene (PS‐PCL‐PDMS‐PCL‐PS) block copolymers with different lengths of PS subchains were synthesized and incorporated into epoxy thermoset. Due to the difference in the length of PS subchains, two different sizes of core‐shell nanostructures were obtained. When these two block copolymers were incorporated into epoxy, the tensile strength, elongation at break, damping temperature in range (tan δ > 0.2), and storage modulus of the epoxy thermoset below 105 °C were simultaneously improved. Meanwhile, the effects of the lengths of PS subchains on the size of nanostructures and the relationship between microstructure and macroscopic properties of epoxy composites were systematically investigated. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46362.
Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for Anti–Human T Lymphotropic Virus Type I Antibody–Positive Rheumatoid Arthritis
Authors: Suzuki Takahisa , Fukui Shoichi , Umekita Kunihiko , Miyamoto Junya , Umeda Masataka , Nishino Ayako , Okada Akitomo , Koga Tomohiro , Kawashiri Shin‐ya , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Fujikawa Keita , Aramaki Toshiyuki , Mizokami Akinari , Matsuoka Naoki , Ueki Yukitaka , Eguchi Katsumi , Sato Shuntaro , Hidaka Toshihiko , Origuchi Tomoki , Okayama Akihiko , Kawakami Atsushi , Nakamura Hideki 
Published: February 2018

ObjectiveTo evaluate the effectiveness of tumor necrosis factor (TNF) inhibitors for the treatment of human T lymphotropic virus type I (HTLV‐I)–positive patients with rheumatoid arthritis (RA) in an area endemic for HTLV‐I infection.MethodsWe conducted an observational study of 585 RA patients in whom TNF inhibitors were newly introduced as a first biologic disease‐modifying antirheumatic drug in an area in southwestern Japan that is endemic for HTLV‐I infection.ResultsFifty patients (8.5%) were anti–HTLV‐I antibody–positive. The ages of the patients in this group were significantly higher at entry compared with the ages of patients who were anti–HTLV‐I antibody–negative (n = 535). The median Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) was 5.21. Among the total group of patients, 82% were anti–citrullinated protein antibody (ACPA)–positive. The persistence rate of TNF inhibitors at 24 weeks was 89%. The median DAS28‐ESR was significantly decreased at 24 weeks in each group. The European League Against Rheumatism (EULAR) response rate was significantly better in the anti–HTLV‐I antibody–negative patients (P = 0.0277). Multiple regression analysis demonstrated that anti–HTLV‐I antibody status was significantly associated with the EULAR response rate and change in the DAS28‐ESR and was prominent especially in the ACPA‐negative subjects. No patients developed adult T cell leukemia/lymphoma (ATL) or HTLV‐I–associated myelopathy (HAM) during the 24‐week treatment period.ConclusionThe efficacy of TNF inhibitors may be attenuated in anti–HTLV‐I antibody–positive patients with RA. ATL and HAM did not develop when TNF inhibitors were used for 24 weeks, but the long‐term risk is not known.
Differences in nonclinical pharmacokinetics between species and prediction of human pharmacokinetics of TAK‐272 (SCO‐272), a novel orally active renin inhibitor
Authors: Ebihara Takuya , Nishihara Mitsuhiro , Takahashi Junzo , Jinno Fumihiro , Tagawa Yoshihiko 
Published: February 2018

AbstractIn the search for orally available drugs, the prediction of human pharmacokinetics (PK) is essential for successfully selecting compounds that will be clinically useful. This report describes the selection of TAK‐272 (SCO‐272), a novel orally active renin inhibitor, as a clinical candidate via the detailed investigation of nonclinical PK data and human PK prediction. The bioavailability (BA) of TAK‐272 after oral administration to rats and monkeys was low, especially in fasted monkeys, and the systemic exposure of TAK‐272 was highly variable in monkeys. The results of mass balance studies in animals suggested that the absorbed TAK‐272 was largely eliminated by metabolism. In vitro studies revealed that TAK‐272 was mainly metabolized by CYP3A4/5 in humans, and it was a P‐glycoprotein substrate. PK analysis suggested that the factors responsible for the low BA were different in rats and monkeys. First‐pass hepatic extraction was high in rats, while the fraction absorbed from the gastrointestinal tract (Fa * Fg) was low in monkeys. It was predicted that humans would have a higher BA and a longer half‐life in the plasma compared with the animals by a simple calculation using intrinsic hepatic clearance in monkeys, which correlates well with human values for CYP3A4 substrates, and Fa * Fg in rats, which correlates relatively well with human values. TAK‐272 was finally selected as a clinical candidate based on the result of human PK prediction. The actual human PK after oral administration of TAK‐272 was comparable to the predicted profile and was preferable for clinical usage.
Income tax and the motivation to work
Authors: Rick Scott , Paolacci Gabriele , Burson Katherine 
Published: February 2018

AbstractDoes income tax influence the motivation to work? We propose that the degree of effort exertion in the presence of income tax depends on people's attitudes toward two key components of taxation: redistribution and government intervention. For people favorable toward both, working while taxed is aligned with personal identity and may actually enhance motivation. All others, however, may find taxes demotivating. In two incentive‐compatible labor experiments, framing wages as subject to an income tax significantly increased productivity among people chronically favorable toward both redistribution and government intervention. For everyone else, taxes did not reliably influence productivity. An objectively equivalent intervention that did not redistribute a portion of participants' wages (framed as a wage “match” rather than a “tax”) did not motivate anyone to work harder. Our findings suggest that the net effect of income tax on productivity partly depends on the distribution of attitudes toward redistribution and government intervention.
Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk using liquid chromatography–tandem mass spectrometry
Authors: Park Jin‐A , Abd El‐Aty A. M. , Zheng Weijia , Kim Seong‐Kwan , Choi Jeong‐min , Hacımüftüoğlu Ahmet , Shim Jae‐Han , Shin Ho‐Chul 
Published: February 2018

AbstractIn this work, a method was developed for the simultaneous determination of residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples were extracted with 0.1% formic acid in acetonitrile, defatted with n‐hexane, and filtered prior to analysis using liquid chromatography–tandem mass spectrometry. The analytes were separated on a C18 column using 0.1% acetic acid and methanol as the mobile phase. The matrix‐matched calibration curves showed good linearity over a concentration range of 5–50 ng/g with coefficients of determination (R2) ≥0.991. The intra‐ and inter‐day accuracies (expressed as recovery percentage values) calculated using three spiking levels (5, 10, and 20 μg/kg) were 80–108.65 and 74.06–107.15%, respectively, and the precisions (expressed as relative standard deviation) were 2.86–13.67 and 0.05–11.74%, respectively, for the tested drugs determined in various matrices. The limits of quantification (1 and 2 μg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that have no specific maximum residue limit (MRL). The developed method was tested using market samples and none of the target analytes was detected in any of the samples. The validated method proved to be practicable for detection of the tested analytes in pork, milk, and eggs.
The current state and future perspectives of cannabinoids in cancer biology
Authors: Śledziński Paweł , Zeyland Joanna , Słomski Ryszard , Nowak Agnieszka 
Published: February 2018

AbstractTo date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.
Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression
Authors: Huang Meixian , Inukai Takeshi , Miyake Kunio , Tanaka Yoichi , Kagami Keiko , Abe Masako , Goto Hiroaki , Minegishi Masayoshi , Iwamoto Shotaro , Sugihara Eiji , Watanabe Atsushi , Somazu Shinpei , Shinohara Tamao , Oshiro Hiroko , Akahane Koshi , Goi Kumiko , Sugita Kanji 
Published: February 2018

AbstractCytosine arabinoside (Ara‐C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara‐C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara‐CTP) as an active form. In the first step of the metabolic pathway, Ara‐C is phosphorylated to Ara‐CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara‐C sensitivity in ALL appears inconclusive. We analyzed various cell lines for the possible involvement of DCK in the sensitivities of B‐cell precursor ALL (BCP‐ALL) to Ara‐C. Higher DCK expression was associated with higher Ara‐C sensitivity. DCK knockout by genome editing with a CRISPR‐Cas9 system in an Ara‐C‐sensitive‐ALL cell line induced marked resistance to Ara‐C, but not to vincristine and daunorubicin, indicating the involvement of DCK expression in the Ara‐C sensitivity of BCP‐ALL. DCK gene silencing due to the hypermethylation of a CpG island and reduced DCK activity due to a nonsynonymous variant allele were not associated with Ara‐C sensitivity. Clofarabine is a second‐generation deoxyadenosine analog rationally synthesized to improve stability and reduce toxicity. The IC50 of clofarabine in 79 BCP‐ALL cell lines was approximately 20 times lower than that of Ara‐C. In contrast to Ara‐C, although the knockout of DCK induced marked resistance to clofarabine, sensitivity to clofarabine was only marginally associated with DCK gene expression level, suggesting a possible efficacy of clofarabine for BCP‐ALL that shows relative Ara‐C resistance due to low DCK expression.
A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Authors: Wang Mengmeng , Gao Yuzhen , Feng Huijuan , Warner Elisa , An Mingrui , Jia Jian'an , Chen Shipeng , Fang Meng , Ji Jun , Gu Xing , Gao Chunfang 
Published: February 2018

AbstractIntrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need. Nomograms present a simple and efficient way to make a discrimination. A total of 2894 patients who underwent surgery for PLC were collected. Of these, 1614 patients formed the training cohort for nomogram construction, and thereafter, 1280 patients formed the validation cohort to confirm the model's performance. Histopathologically confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two cohorts, respectively. A nomogram integrating six easily obtained variables (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha‐fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19‐9) is proposed in accordance with Akaike's Information Criterion (AIC). A score of 15 was determined as the cut‐off value, and the corresponding discrimination efficacy was sufficient. Additionally, patients who scored higher than 15 suffered poorer prognosis than those with lower scores, regardless of the subtype of PLC. A nomogram for clinical discrimination of ICC and HCC has been established, where a higher score indicates ICC and poor prognosis. Further application of this nomogram in multicenter investigations may confirm the practicality of this tool for future clinical use.
Chromosomal abnormality variation detected by G‐banding is associated with prognosis of diffuse large B‐cell lymphoma treated by R‐CHOP‐based therapy
Authors: Mizuno Yoshimi , Tsukamoto Taku , Kawata Eri , Uoshima Nobuhiko , Uchiyama Hitoji , Yokota Isao , Maegawa Saori , Takimoto Tomoko , Tanba Kazuna , Matsumura‐Kimoto Yayoi , Kuwahara‐Ota Saeko , Fujibayashi Yuto , Yamamoto‐Sugitani Mio , Chinen Yoshiaki , Shimura Yuji , Horiike Shigeo , Taniwaki Masafumi , Kobayashi Tsutomu , Kuroda Junya 
Published: February 2018

AbstractDiffuse large B‐cell lymphoma (DLBCL), which is the most prevalent disease subtype of non‐Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic and molecular features. This study retrospectively investigated the clinical impact of G‐banding‐defined chromosomal abnormality on treatment outcomes of DLBCL in the era of rituximab‐containing immunochemotherapy. Of 181 patients who were diagnosed with DLBCL and treated with R‐CHOP or an R‐CHOP‐like regimen between January 2006 and April 2014, metaphase spreads were evaluable for G‐banding in 120. In these 120 patients, 40 were found to harbor a single chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs), which are defined by the presence of different types of chromosomal abnormalities in G‐banding, including 19 with two CAVs and 44 with ≥3 CAVs; and 17 had normal karyotypes. No specific chromosomal break point or numerical abnormality was associated with overall survival (OS) or progression‐free survival (PFS), but the presence of ≥3 CAVs was significantly associated with inferior OS rates (hazard ratio (HR): 2.222, 95% confidence interval (CI): 1.056–4.677, P = 0.031) and tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965–3.344, P = 0.061). In addition, ≥3 CAVs more frequently accumulated in high‐risk patients, as defined by several conventional prognostic indices, such as the revised International Prognostic Index. In conclusion, our results suggest that the emergence of more CAVs, especially ≥3, based on chromosomal instability underlies the development of high‐risk disease features and a poor prognosis in DLBCL.
Treatment‐related mortality in newly diagnosed pediatric cancer: a population‐based analysis
Authors: Gibson Paul , Pole Jason D. , Lazor Tanya , Johnston Donna , Portwine Carol , Silva Mariana , Alexander Sarah , Sung Lillian ,   the International Pediatric Oncology Mortality Classification (IPOMC) Group
Published: February 2018

AbstractUsing a previously developed reliable and valid treatment‐related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population‐based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event. Among the 5179 children included, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3–4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6–4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5‐year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.
Risk factors and survival outcomes in patients with breast cancer and lung metastasis: a population‐based study
Authors: Xiao Weikai , Zheng Shaoquan , Liu Peng , Zou Yutian , Xie Xinhua , Yu Ping , Tang Hailin , Xie Xiaoming 
Published: February 2018

AbstractThe risk factors for morbidity and mortality in breast cancer lung metastases (BCLM) patients still remain poorly identified. The aim of this study was to assess the incidence and survival of BCLM and associated risk factors. Patients with BCLM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic regression analysis was used to determine the risk factors for BCLM. Predictors of factors associated with death were analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases confined to lungs. The median survival time for patients with BCLM was 21 months, and 15.5% of the patients were alive more than 3 years. The tumor subtype distribution was 45.3% HR−/HER2−, 12.2% HR+/HER2+, 7.8% HR−/HER2+, and 15.0% triple‐negative subtype. Compared with patients without BCLM, those with BCLM were more likely to be aged, female, black, higher tumor grade, HR−/HER2+, HR+/HER2+, and triple‐negative subtypes at diagnosis. Survival analysis showed that the aged, black race, HR−/HER2+, triple‐negative subtype, higher grade were the independent risk factor for BCLM patients’ survival, while HR+/HER2+ subtype, insured status, and married status suggested better prognosis. In conclusion, the incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly patients with HER2‐positive or triple‐negative tumors were more likely to have BCLM.
Employment benefits and job retention: evidence among patients with colorectal cancer
Authors: Veenstra Christine M. , Abrahamse Paul , Wagner Todd H. , Hawley Sarah T. , Banerjee Mousumi , Morris Arden M. 
Published: February 2018

AbstractA “health shock,” that is, a large, unanticipated adverse health event, can have long‐term financial implications for patients and their families. Colorectal cancer is the third most commonly diagnosed cancer among men and women and is an example of a specific health shock. We examined whether specific benefits (employer‐based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer. In 2011–14, we surveyed patients with Stage III colorectal cancer from two representative SEER registries. The final sample was 1301 patients (68% survey response rate). For this study, we excluded 735 respondents who were not employed and 20 with unknown employment status. The final analytic sample included 546 respondents. Job retention in the year following diagnosis was assessed, and multivariable logistic regression was used to evaluate associations between job retention and access to specific employment benefits. Employer‐based health insurance (OR = 2.97; 95% CI = 1.56–6.01; P = 0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23–6.98; P = 0.015) were significantly associated with job retention, after adjusting for sociodemographic, clinical, geographic, and job characteristics.
Optimizing Water Exchange Rates and Rotational Mobility for High‐Relaxivity of a Novel Gd‐DO3A Derivative Complex Conjugated to Inulin as Macromolecular Contrast Agents for MRI
Authors: Granato Luigi , Vander Elst Luce , Henoumont Celine , Muller Robert N. , Laurent Sophie 
Published: February 2018

Thanks to the understanding of the relationships between the residence lifetime τM of the coordinated water molecules to macrocyclic Gd‐complexes and the rotational mobility τR of these structures, and according to the theory for paramagnetic relaxation, it is now possible to design macromolecular contrast agents with enhanced relaxivities by optimizing these two parameters through ligand structural modification. We succeeded in accelerating the water exchange rate by inducing steric compression around the water binding site, and by removing the amide function from the DOTA‐AA ligand [1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid mono(p‐aminoanilide)] (L) previously designed. This new ligand 10[2(1‐oxo‐1‐p‐propylthioureidophenylpropyl]‐1,4,7,10‐tetraazacyclodecane‐1,4,7‐tetraacetic acid (L1) was then covalently conjugated to API [O‐(aminopropyl)inulin] to get the complex API‐(GdL1)x with intent to slow down the rotational correlation time (τR) of the macromolecular complex. The evaluation of the longitudinal relaxivity at different magnetic fields and the study of the 17O‐NMR at variable temperature of the low‐molecular‐weight compound (GdL1) showed a slight decrease of the τM value ( = 331 ns vs. = 450 ns for the GdL complex). Consequently to the increase of the size of the API‐(GdL1)x complex, the rotational correlation time becomes about 360 times longer compared to the monomeric GdL1 complex (τR = 33,700 ps), which results in an enhanced proton relaxivity.