bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity
Authors: Boyle Samantha E. , Fedele Clare G. , Corbin Vincent , Wybacz Elisha , Szeto Pacman , Lewin Jeremy , Young Richard J. , Wong Annie , Fuller Robert , Spillane John , Speakman David , Donahoe Simon , Pohl Miklos , Gyorki David , Henderson Michael A. , Johnstone Ricky W. , Papenfuss Anthony T. , Shackleton Mark 
Published: June 2016

Abstract
The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations. We found that CD271− and CD271+ melanoma cells from each of seven patients were similarly tumorigenic, regardless of assay variations. Surprisingly variable CD271 expression patterns were observed in the analyses of sibling PDX tumors (n = 68) grown in the same experiments from either CD271− or CD271+ cells obtained from patients. This indicates unstable intratumoral lineage relationships between CD271− and CD271+ melanoma cells that are inconsistent with classical, epigenetically based theories of disease progression, such as the cancer stem cell and plasticity models. SNP genotyping of pairs of sibling PDX tumors grown from phenotypically identical CD271− or CD271+ cells showed large pairwise differences in copy number (28%–48%). Differences were also apparent in the copy number profiles of CD271− and CD271+ cells purified directly from each of the four melanomas (1.4%–23%). Thus, CD271 expression in patient melanomas is unstable, not consistently linked to increased tumorigenicity and associated with genetic heterogeneity, undermining its use as a marker in clinical studies. Cancer Res; 76(13); 3965–77. ©2016 AACR.
PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma
Authors: Agnihotri Sameer , Golbourn Brian , Huang Xi , Remke Marc , Younger Susan , Cairns Rob A. , Chalil Alan , Smith Christian A. , Krumholtz Stacey-Lynn , Mackenzie Danielle , Rakopoulos Patricia , Ramaswamy Vijay , Taccone Michael S. , Mischel Paul S. , Fuller Gregory N. , Hawkins Cynthia , Stanford William L. , Taylor Michael D. , Zadeh Gelareh , Rutka James T. 
Published: June 2016

Abstract
Proliferating cancer cells are characterized by high rates of glycolysis, lactate production, and altered mitochondrial metabolism. This metabolic reprogramming provides important metabolites for proliferation of tumor cells, including glioblastoma. These biological processes, however, generate oxidative stress that must be balanced through detoxification of reactive oxygen species (ROS). Using an unbiased retroviral loss-of-function screen in nontransformed human astrocytes, we demonstrate that mitochondrial PTEN-induced kinase 1 (PINK1) is a regulator of the Warburg effect and negative regulator of glioblastoma growth. We report that loss of PINK1 contributes to the Warburg effect through ROS-dependent stabilization of hypoxia-inducible factor-1A and reduced pyruvate kinase muscle isozyme 2 activity, both key regulators of aerobic glycolysis. Mechanistically, PINK1 suppresses ROS and tumor growth through FOXO3a, a master regulator of oxidative stress and superoxide dismutase 2. These findings highlight the importance of PINK1 and ROS balance in normal and tumor cells. PINK1 loss was observed in a significant number of human brain tumors including glioblastoma (n &gt; 900) and correlated with poor patient survival. PINK1 overexpression attenuates in vivo glioblastoma growth in orthotopic mouse xenograft models and a transgenic glioblastoma model in Drosophila. Cancer Res; 76(16); 4708–19. ©2016 AACR.
Thrombosis in Cancer: Research Priorities Identified by a National Cancer Institute/National Heart, Lung, and Blood Institute Strategic Working Group
Authors: Key Nigel S. , Khorana Alok A. , Mackman Nigel , McCarty Owen J.T. , White Gilbert C. , Francis Charles W. , McCrae Keith R. , Palumbo Joseph S. , Raskob Gary E. , Chan Andrew T. , Sood Anil K. 
Published: June 2016

Abstract
The risk for venous thromboembolism (VTE) is increased in cancer and particularly with chemotherapy, and it portends poorer survival among patients with cancer. However, many fundamental questions about cancer-associated VTE, or Trousseau syndrome, remain unanswered. This report summarizes the proceedings of a working group assembled by the NCI and NHLBI in August 2014 to explore the state of the science in cancer-associated VTE, identify clinically important research gaps, and develop consensus on priorities for future research. Representing a convergence of research priorities between the two NIH Institutes, the workshop addressed epidemiologic, basic science, clinical, and translational issues in cancer-associated VTE. Cancer Res; 76(13); 3671–5. ©2016 AACR.
A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer
Authors: LaBonte Melissa J. , Yang Dongyun , Zhang Wu , Wilson Peter M. , Nagarwala Yasir M. , Koch Kevin M. , Briner Colleen , Kaneko Tomomi , Rha Sun-Young , Gladkov Oleg , Urba Susan G. , Sakaeva Dina , Pishvaian Michael J. , Hsieh Ruey-Kuen , Lee Wei-Ping , Lenz Heinz-Josef 
Published: June 2016

Abstract
An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m2 twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther; 15(9); 2251–8. ©2016 AACR.
ЕКОЛОГО-БІОЛОГІЧНІ, ЕПІДЕМІОЛОГІЧНІ ТА КЛІНІЧНІ АСПЕКТИ ЕНДЕМІЧНОГО ОСЕРЕДКУ ОПІСТОРХОЗУ В СУМСЬКІЙ ОБЛАСТІ
Authors: Chemych M. D. , Fotina T. I. , Fotina H. A. , Ilyina N. I. , Nazarenko S. M. , Ilyina V. V. , Frolova L. S. 
Published: June 2016

<p class="1"><em>На території Сумської області зареєстровано 4 види опісторхід: Opisthorchis felineus, Pseudamphisto­mum truncatum, Metorchis bilis і Metorchis xanthosomus. Встановлено, що осередки опісторхідозів в умовах досліджуваної території прив’язані, в першу чергу, до малих річок. Марити опісторхід у природних екосистемах Сумської області зареєстровані у 5 видів м’ясоїдних ссавців. В антропогенних екосистемах Сумської області провідну роль у циркуляції опісторхід відіграють домашні коти. Проведена оцінка зараження коропових риб метацеркаріями опісторхід. Встановлено, що домінантними з точки зору зараження і накопичення метацеркарій опісторхід є 3 види коропових риб: плітка, краснопірка і уклейка. Опісторхоз переважно перебігає латентно. З маніфестних форм хвороби найчастіше виявляється холецистит (78,6 %). Вирішальну роль у діагностиці хронічного опісторхозу має копроовоскопія (100 %). Групу ризику складають рибалки та члени їх сімей (71,9 %). Основним фактором передавання є солена та в’ялена риба.</em></p>
АЛЬТЕРНАТИВНИЙ ЗАСІБ САНАЦІЇ РЕЗИДЕНТНИХ НОСІЇВ ЗОЛОТИСТОГО СТАФІЛОКОКА
Authors: Kotsar O. V. , Kochneva O. V. , Dolhova T. S. , Maluchenko A. Yu. 
Published: June 2016

<p class="1"><em><span>Роль золотистого стафілокока в етіологічній структурі гнійно-запальних інфекцій має особливе значення. Актуальною проблемою залишається вибір способу боротьби з бактеріоносіями. Одним з альтернативних шляхів є використання бактеріофагів. У ході дослідження була визначена чутливість штамів Staphylococcus аureus, вилучених від студентів-медиків Харківського національного медичного університету (ХНМУ), до дії бактеріофагів різних виробників. Чутливість визначали диско-дифузійним методом до таких бактеріофагів: стафілофаг (ФДУП «НВО «Микроген» МОЗ РФ, випуск м. Перм), піофаг (ФДУП «НВО «Микроген» МОЗ РФ, випуск м. Нижній Новгород) і стафілококовий бактеріофаг (фармацевтичний завод «Біофарм», м. Біла Церква, Україна). Результати дослідження показали, що більш ніж половина виділених штамів S. aureus, (68,75±6,69) %, були чутливими до стафілофага українського виробництва, до піофага та стафілофага російського виробника встановлена низька чутливість – (45,83±7,19) та (22,90±6,06) % відповідно.</span></em></p>
Real-Time Flood Forecasting and Information System for the State of Iowa
Authors: Krajewski Witold F. , Ceynar Daniel , Demir Ibrahim , Goska Radoslaw , Kruger Anton , Langel Carmen , Mantilla Ricardo , Niemeier James , Quintero Felipe , Seo Bong-Chul , Small Scott J. , Weber Larry J. , Young Nathan C. 
Published: June 2016

Abstract
The Iowa Flood Center (IFC), established following the 2008 record floods, has developed a real-time flood forecasting and information dissemination system for use by all Iowans. The system complements the operational forecasting issued by the National Weather Service, is based on sound scientific principles of flood genesis and spatial organization, and includes many technological advances. At its core is a continuous rainfall–runoff model based on landscape decomposition into hillslopes and channel links. Rainfall conversion to runoff is modeled through soil moisture accounting at hillslopes. Channel routing is based on a nonlinear representation of water velocity that considers the discharge amount as well as the upstream drainage area. Mathematically, the model represents a large system of ordinary differential equations organized to follow river network topology. The IFC also developed an efficient numerical solver suitable for high-performance computing architecture. The solver allows the IFC to update forecasts every 15 min for over 1,000 Iowa communities. The input to the system comes from a radar-rainfall algorithm, developed in-house, that maps rainfall every 5 min with high spatial resolution. The algorithm uses Level II radar reflectivity and other polarimetric data from the Weather Surveillance Radar-1988 Dual-Polarimetric (WSR-88DP) radar network. A large library of flood inundation maps and real-time river stage data from over 200 IFC “stream-stage sensors” complement the IFC information system. The system communicates all this information to the general public through a comprehensive browser-based and interactive platform. Streamflow forecasts and observations from Iowa can provide support for a similar system being developed at the National Water Center through model intercomparisons, diagnostic analyses, and product evaluations.
Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study
Authors: Seminog Olena O , Ogunlaja Oyindamola I , Yeates David , Goldacre Michael J 
Published: June 2016

Objective Case reports suggest that there may be an increased risk of some cancers associated with sickle cell disease. However, population-based studies are scarce and there is no comprehensive enumeration of the risks across the whole range of site-specific cancers. Our aim was to provide this. Design We used an English national dataset of linked statistical records of hospital admissions and deaths from 1999 to 2011 to undertake a retrospective cohort study. Setting England. Participants Records of all hospital admissions in England with SCD or with conditions included in the control cohort. Main outcome measures Rate ratios were calculated comparing rates of cancer in a sickle cell disease cohort and a control cohort, confining the analyses to people whose ethnicity was recorded as Black. Results Comparing the sickle cell disease cohort with the cohort without sickle cell disease, the rate ratio for all cancers combined was 2.1 (95% confidence interval 1.7–2.5). There were significantly high rate ratios for haematological malignancies, including Hodgkin’s lymphoma (rate ratio 3.7, 1.5–8.4), non-Hodgkin’s lymphoma (2.6, 1.3–4.8), multiple myeloma (5.5, 2.8–10.1), lymphoid leukaemia (3.3, 1.3–8.0) and myeloid leukaemia (10.0, 4.6–21.5). Four solid tumours showed elevated rate ratios: colon cancer (2.8, 1.2–5.5), non-melanoma skin cancer (4.4, 1.3–12.2), kidney cancer (5.4, 2.3–11.5) and thyroid cancer (5.1, 1.3–15.4). Conclusions The risk of some malignancies may be raised in patients with sickle cell disease. However, this study was based on administrative data without the scope to validate these against patients’ full clinical records. Our findings need confirmation or refutation. If confirmed, work to elucidate, at the genetic and molecular level, why people with sickle cell disease have elevated risks of individual cancers might make contributions to the fundamental understanding of carcinogenesis.
Dealing with the Complexity of Causes of Societal Innovativeness: Social Enabling and Disabling Mechanisms and the Case of China
Authors: Redding Gordon , Drew Antony 
Published: June 2016

Societies progress by the influence of two forces: innovativeness and cooperativeness. A capacity for enabling these forces constitutes a society’s transformative capacity. The article proposes a vocabulary for certain universal requirements for use in comparing the various societal trajectories aiming towards shared prosperity. Progress to date has in consequence normally seen the growth of empowerment and of more benevolent forms of domination over time. Economic action fosters the sharing of prosperity when systems encourage competition to cooperate. Studies that stress the heritage of ecological context in shaping relevant responses in the present-day social psychology are considered. The specific field of innovativeness is considered by an analysis of Silicon Valley. From this, and from other studies, seven features are identified for an ideal type of societal system high on innovativeness. These are capacity to scale up, worker creativity, individual autonomy, property rights and incentive, open society, stable institutional order and rationality. China is assessed against these criteria, and found to have certain inadequacies that are currently the subject of policy attention. JEL: Z1, N00, O01, P5
Pain Resolution After Hallux Valgus Surgery
Authors: Chen Jerry Yongqiang , Ang Benjamin Fu Hong , Jiang Lei , Yeo Nicholas Eng Meng , Koo Kevin , Singh Rikhraj Inderjeet 
Published: June 2016

Background: Although more than 1500 publications on hallux valgus can be found in the current literature, none of them have reported on the course of pain resolution after hallux valgus surgery. Thus, this study aimed to investigate pain resolution after hallux valgus surgery and to identify predictive factors associated with residual pain at 6 months after surgery. Methods: We prospectively followed up 308 patients who underwent hallux valgus surgery at a tertiary hospital at 6 months and 2 years after surgery. Multivariate logistic regression analysis was performed to evaluate the risk factors associated with residual pain after surgery. Results: Ninety-four patients (31%) had some degree of residual pain at 6 months after surgery. After excluding 4 patients who developed osteoarthritis of the first metatarsophalangeal joint over the next 18 months, 73 of the remaining 90 (81%) experienced improvement in visual analog scale (VAS) by the 2-years follow-up. Their median VAS improved from 4 (interquartile range [IQR] 3, 5) at 6 months to 0 (IQR 0, 3) at 2 years ( P < .001). A higher preoperative VAS increased the risk of having persistent pain at 6 months after sugery (odds ratio [OR] 1.388, 95% confidence interval [CI] 1.092, 1.764, P = .007), whereas a higher preoperative Mental Component Score of SF-36 (MCS) reduced this risk (OR 0.952, 95% CI 0.919, 0.987, P = .007). Conclusions: As much as 31% of patients will have residual pain at 6 months after surgery. Preoperative VAS and MCS are predictors for residual pain. However, these patients will continue to improve over the next 18 months, with 71% of them being pain free at 2 years after surgery. Level of Evidence: Level II, prospective comparative study.
Retrospective application of Program to Access and Review Trending iNformation and Evaluate coRrelation to Symptoms in patients with Heart Failure criteria for the remote management of patients with cardiac resynchronisation therapy
Authors: Brasca Francesco MA , Franzetti Jessica , Rella Valeria , Malfatto Gabriella , Brambilla Roberto , Facchini Mario , Parati Gianfranco , Perego Giovanni B 
Published: June 2016

Aim The Program to Access and Review Trending iNformation and Evaluate coRrelation to Symptoms in patients with Heart Failure (PARTNERS HF) trial elaborated a multiparametric model for prediction of acute decompensation in advanced heart failure patients, based on periodical in office data download from cardiac resynchronisation devices. In this study, we evaluated the ability of the PARTNERS HF criteria to detect initial decompensation in a population of moderate heart failure patients under remote monitoring. Methods We retrospectively applied the PARTNERS HF criteria to 1860 transmissions from 104 patients (median follow up 21 months; range 1–67 months), who were enrolled in our programme of telemedicine after cardiac resynchronisation therapy. We tested the ability of a score based on these criteria to predict any acute clinical decompensation occurring in the 15 days following a transmission. Results In 441 cases, acute heart failure was diagnosed after the index transmission. The area under the curve (AUC) of the score for the diagnosis of acute decompensation was 0.752 (confidence interval (CI) 95% 0.728–0.777). The best score cut-off was consistent with the results of PARTNERS HF: with a score ≥2, sensitivity was 75% and specificity 68%. The odds ratio for events was 6.24 (CI 95% 4.90–7.95; p < 0.001). Conclusions When retrospectively applied to remote monitoring transmissions and arranged in a score, PARTNERS HF criteria could identify HF patients who subsequently developed acute decompensation. These results warrant prospective studies applying PARTNERS HF criteria to remote monitoring.
Utility and Usability of the Rapid Assessment of Hospital Procurement Barriers in Donation (RAPiD) as a Tool for OPO Hospital Development Staff
Authors: Alolod Gerard P. , Traino Heather M. , Siminoff Laura A. 
Published: June 2016

Context: Few systematic assessment tools are available to organ procurement organizations (OPOs) for evaluating donation climates of hospitals in their donation service areas (DSAs). The Rapid Assessment of hospital Procurement barriers in Donation (RAPiD) was developed for OPO hospital development staff to assess the organ donation climate of hospitals. Objective: To implement a national test of the RAPiD to examine its efficacy and usability by OPO hospital development staff. Design: Two-arm randomized design, comparing implementation of RAPiD protocol between qualitatively trained researchers (n = 7) and OPO hospital development staff (n = 24); all evaluators received the same training assessments of high-yield hospitals. Setting: A total of 77 hospitals in DSAs of 8 OPOs. Participants: A total of 2552 health-care providers (HCPs) in high organ donor potential units. Main Outcome Measures: Twenty-four donation-related attitudes, knowledge, and behaviors. Results: More HCPs interviewed in the autonomous condition were positive toward the concept of organ donation. However, HCPs in the assisted condition were more candid about and critical of the OPO. As for knowledge, fewer HCPs in the autonomous condition reported familiarity with the donation process, need for donors, and generally accepted timely referral criteria. With respect to behaviors, more respondents in the autonomous condition reported frequent or occasional contact with the OPO and routine or occasional referral criteria use. Due to issues of bias, inadequate research experience, conflicts of interest, and ongoing OPO hospital development initiatives, the RAPiD’s usability by OPO-based hospital development staff is questionable and not recommended in its current form. A next generation of the RAPiD is described for future consideration.
Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects
Authors: Castle Jessica R. , Youssef Joseph El , Branigan Deborah , Newswanger Brett , Strange Poul , Cummins Martin , Shi Leon , Prestrelski Steven 
Published: June 2016

Background: There is currently no stable liquid form of glucagon commercially available. The aim of this study is to assess the speed of absorption and onset of action of G-Pump™ glucagon at 3 doses as compared to GlucaGen®, all delivered subcutaneously via an OmniPod®. Methods: Nineteen adult subjects with type 1 diabetes participated in this Phase 2, randomized, double-blind, cross-over, pharmacokinetic/pharmacodynamic study. Subjects were given 0.3, 1.2, and 2.0 µg/kg each of G-Pump glucagon and GlucaGen via an OmniPod. Results: G-Pump glucagon effectively increased blood glucose levels in a dose-dependent fashion with a glucose Cmax of 183, 200, and 210 mg/dL at doses of 0.3, 1.2, and 2.0 µg/kg, respectively ( P = ns vs GlucaGen). Mean increases in blood glucose from baseline were 29.2, 52.9, and 77.7 mg/dL for G-Pump doses of 0.3, 1.2, and 2.0 µg/kg, respectively. There were no statistically significant differences between treatments in the glucose T50%-early or glucagon T50%-early with one exception. The glucagon T50%-early was greater following G-Pump treatment at the 2.0 μg/kg dose (13.9 ± 4.7 min) compared with GlucaGen treatment at the 2.0 μg/kg dose (11.0 ± 3.1 min, P = .018). There was more pain and erythema at the infusion site with G-Pump as compared to GlucaGen. No serious adverse events were reported, and no unexpected safety issues were observed. Conclusions: G-Pump glucagon is a novel, stable glucagon formulation with similar PK/PD properties as GlucaGen, but was associated with more pain and infusion site reactions as the dose increased, as compared to GlucaGen.