bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized Management of Pancreatic Ductal Adenocarcinoma Patients through Computational Modeling
Authors: Yamamoto Kimiyo N. , Yachida Shinichi , Nakamura Akira , Niida Atsushi , Oshima Minoru , De Subhajyoti , Rosati Lauren M. , Herman Joseph M. , Iacobuzio-Donahue Christine A. , Haeno Hiroshi 
Published: April 2017

Abstract
Phenotypic diversity in pancreatic ductal adenocarcinoma (PDAC) results in a variety of treatment responses. Rapid autopsy studies have revealed a subgroup of PDAC patients with a lower propensity to develop metastatic disease, challenging the common perception that all patients die of widely metastatic disease, but questions remain about root causes of this difference and the potential impact on treatment strategies. In this study, we addressed these questions through the development of a mathematical model of PDAC progression that incorporates the major alteration status of specific genes with predictive utility. The model successfully reproduced clinical outcomes regarding metastatic patterns and the genetic alteration status of patients from two independent cohorts from the United States and Japan. Using this model, we defined a candidate predictive signature in patients with low metastatic propensity. If a primary tumor contained a small fraction of cells with KRAS and additional alterations to CDKN2A, TP53, or SMAD4 genes, the patient was likely to exhibit low metastatic propensity. By using this predictive signature, we computationally simulated a set of clinical trials to model whether this subgroup would benefit from locally intensive therapies such as surgery or radiation therapy. The largest overall survival benefit resulted from complete resection, followed by adjuvant chemoradiation therapy and salvage therapies for isolated recurrence. While requiring prospective validation in a clinical trial, our results suggest a new tool to help personalize care in PDAC patients in seeking the most effective therapeutic modality for each individual. Cancer Res; 77(12); 3325–35. ©2017 AACR.
Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
Authors: Ose Jennifer , Poole Elizabeth M. , Schock Helena , Lehtinen Matti , Arslan Alan A. , Zeleniuch-Jacquotte Anne , Visvanathan Kala , Helzlsouer Kathy , Buring Julie E. , Lee I-Min , Tjønneland Anne , Dossus Laure , Trichopoulou Antonia , Masala Giovanna , Onland-Moret N. Charlotte , Weiderpass Elisabete , Duell Eric J. , Idahl Annika , Travis Ruth C. , Rinaldi Sabina , Merritt Melissa A. , Trabert Britton , Wentzensen Nicolas , Tworoger Shelley S. , Kaaks Rudolf , Fortner Renée T. 
Published: April 2017

Abstract
Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case–control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02–1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03–1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60–0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC. Cancer Res; 77(14); 3951–60. ©2017 AACR.
von Willebrand factor deficiency leads to impaired blood flow recovery after ischaemia in mice
Authors: de Vries Margreet R. , Peters Erna A. B. , Quax Paul H. A. , Nossent A. Yaël 
Published: April 2017

SummaryNeovascularisation, i. e. arteriogenesis and angiogenesis, is an inflammatory process. Therefore attraction and extravasation of leukocytes is essential for effective blood flow recovery after ischaemia. Previous studies have shown that von Willebrand factor (VWF) is a negative regulator of angiogenesis. However, it has also been shown that VWF facilitates leukocyte attraction and extravasation. We aimed to investigate the role of VWF in arteriogenesis and angiogenesis during post-ischaemic neovascularisation. Wild-type (WT) and VWF deficient (VWF-/-) C57BL/6 mice were subjected to hindlimb ischaemia via double ligation of the left femoral artery, and blood flow recovery was followed over time, using Laser Doppler Perfusion Imaging. Blood flow recovery was impaired in VWF-/- mice. After 10 days, VWF-/- mice showed a 43 ± 5% recovery versus 68 ± 5% in WT. Immunohistochemistry revealed that both arteriogenesis in the adductor muscles and angiogenesis in the gastrocnemius muscles were reduced in VWF-/- mice. Furthermore, leukocyte infiltration in the affected adductor muscles was reduced in VWF-/- mice. Residual paw perfusion directly after artery ligation was also reduced in VWF-/- mice, indicating a decrease in pre-existing collateral arteriole density. When we quantified collateral arterioles, we observed a 31% decrease in the average number of collateral arterioles in the pia mater compared to WT mice (57 ± 3 in WT vs 40 ± 4 pial collaterals in VWF-/-). We conclude that VWF facilitates blood flow recovery in mice. VWF deficiency hampers both arteriogenesis and angiogenesis in a hindlimb ischaemia model. This is associated with impaired leukocytes recruitment and decreased pre-existing collateral density in the absence of VWF.
Characteristics of dyspnoea and associated clinical outcomes in the CHAMPION PHOENIX study
Authors: Parker William A. , Bhatt Deepak L. , Prats Jayne , Day Jonathan R. S. , Steg Philippe Gabriel , Stone Gregg W. , Hamm Christian W. , Mahaffey Kenneth W. , Price Matthew J. , Michael Gibson C. , White Harvey D. , Storey Robert F. ,   the CHAMPION PHOENIX Investigators
Published: April 2017

SummaryDyspnoea may be induced by some reversibly-binding P2Y12 inhibitors, including cangrelor and ticagrelor. Dyspnoea was not associated with any compromise to the efficacy of ticagrelor in the PLATO study. The CHAMPION PHOENIX study (NCT01156571) compared initial treatment with cangrelor versus initial treatment with clopidogrel in patients undergoing PCI. We investigated the incidence, characteristics, and associated clinical outcomes in patients with dyspnoea in CHAMPION PHOENIX. Adverse events (AEs) of dyspnoea to 48 hours were recorded in patients randomised to cangrelor or clopidogrel in CHAMPION PHOENIX. The composite primary endpoint of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis as well its individual components were assessed in patients who did or did not report dyspnoea. A total of 68 (1.2 %) cangrelor-treated patients and 18 (0.3 %) clopidogrel-treated patients reported dyspnoea (p<0.001). Most dyspnoea events in cangrelor-treated patients were considered mild (71 %) or moderate (28 %) and only one event was considered severe and led to discontinuation of cangrelor. The dyspnoea events in the clopidogrel-treated patients were mild (78 %) or moderate (22 %). Characteristics of dyspnoea were consistent with those seen in the CHAMPION programme as a whole. In the modified intention-to-treat population, rates of the composite primary outcome and its individual components were not affected by the presence of dyspnoea in cangrelor-treated patients. Cangrelor-related dyspnoea is transient, usually mild or moderate, and unlikely to lead to discontinuation of therapy. The occurrence of dyspnoea does not seem to be associated with any reduction in the efficacy of cangrelor compared with clopidogrel as initial therapy in PCI patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
Toward an Integrated Set of Surface Meteorological Observations for Climate Science and Applications
Authors: Thorne P. W. , Allan R. J. , Ashcroft L. , Brohan P. , Dunn R. J. H , Menne M. J. , Pearce P. R. , Picas J. , Willett K. M. , Benoy M. , Bronnimann S. , Canziani P. O. , Coll J. , Crouthamel R. , Compo G. P. , Cuppett D. , Curley M. , Duffy C. , Gillespie I. , Guijarro J. , Jourdain S. , Kent E. C. , Kubota H. , Legg T. P. , Li Q. , Matsumoto J. , Murphy C. , Rayner N. A. , Rennie J. J. , Rustemeier E. , Slivinski L. C. , Slonosky V. , Squintu A. , Tinz B. , Valente M. A. , Walsh S. , Wang X. L. , Westcott N. , Wood K. , Woodruff S. D. , Worley S. J. 
Published: April 2017

AbstractObservations are the foundation for understanding the climate system. Yet, currently available land meteorological data are highly fractured into various global, regional, and national holdings for different variables and time scales, from a variety of sources, and in a mixture of formats. Added to this, many data are still inaccessible for analysis and usage. To meet modern scientific and societal demands as well as emerging needs such as the provision of climate services, it is essential that we improve the management and curation of available land-based meteorological holdings. We need a comprehensive global set of data holdings, of known provenance, that is truly integrated both across essential climate variables (ECVs) and across time scales to meet the broad range of stakeholder needs. These holdings must be easily discoverable, made available in accessible formats, and backed up by multitiered user support. The present paper provides a high-level overview, based upon broad community input, of the steps that are required to bring about this integration. The significant challenge is to find a sustained means to realize this vision. This requires a long-term international program. The database that results will transform our collective ability to provide societally relevant research, analysis, and predictions in many weather- and climate-related application areas across much of the globe.
Twentieth-Century Trends in the Annual Cycle of Temperature across the Northern Hemisphere
Authors: Cornes Richard C. , Jones Philip D. , Qian Cheng 
Published: April 2017

AbstractThe annual cycle of surface air temperature is examined across Northern Hemisphere land areas (north of 25°N) by comparing the results from the Climatic Research Unit Time Series (CRU TS) dataset against four reanalysis datasets: two versions of the NOAA Twentieth Century Reanalysis (20CR and 20CRC) and two versions of the ECMWF Twentieth Century Reanalysis, version 2 (ERA-20C) and version 2c (ERA-20CM). The modulated annual cycle is adaptively derived from an ensemble empirical mode decomposition (EEMD) filter, and is used to define the phase and amplitude of the annual cycle. The EEMD method does not impose a simple sinusoidal shape of the annual cycle. None of the reanalysis simulations assimilates surface temperature or land-use data. However, they differ in the parameters that are included: both ERA-20C and 20CR assimilate surface pressure data; ERA-20C also includes surface wind data over the oceans; and ERA-20CM does not assimilate any of these synoptic data. It is demonstrated that synoptic variability is critical for explaining the trends and variability of the annual cycle of surface temperature across the Northern Hemisphere. The CMIP5 forcings alone are insufficient to explain the observed trends and decadal-scale variability, particularly with respect to the decline in the amplitude of the annual cycle throughout the twentieth century. The variability in the annual cycle during the latter half of the twentieth century was unusual in the context of the twentieth century, and was most likely related to large-scale atmospheric variability, although uncertainty in the results is greatest before about 1930.
Estimation of Kinetic Energy Dissipation from Breaking Waves in the Wave Crest Region
Authors: Lee J. H. , Monty J. P. , Elsnab J. , Toffoli A. , Babanin A. V. , Alberello A. 
Published: April 2017

AbstractWave-induced turbulence due to breaking in the absence of surface shear stresses is investigated experimentally. A high-fidelity particle image velocimetry (PIV) technique is used to measure the turbulence near the water surface, inside the wave crests. The spatial velocity vector fields of the breaking waves acquired from PIV provide accurate vertical velocity profiles near the air–water interface, as well as wavenumber velocity spectra beneath the breaking waves at different depths. These velocity spectra exhibit a Kolmogorov interval at high wavenumbers, indicating the presence of isotropic turbulence and permitting an estimation of energy dissipation rates. The depth dependence of dissipation rates of the breaking waves generated in the laboratory shows a scaling similar to that found in wind-forced breaking waves in the field. A phase dependence in the dissipation rates of turbulence kinetic energy is also observed, which should be considered to improve the accuracy of the estimated and modeled wave energy dissipation.
AMP-activated kinase and the endogenous endocannabinoid system might contribute to antinociceptive effects of prolonged moderate caloric restriction in mice
Authors: King-Himmelreich Tanya S , Möser Christine V , Wolters Miriam C , Schmetzer Julia , Möller Moritz , Schreiber Yannik , Ferreirós Nerea , Geisslinger Gerd , Niederberger Ellen 
Published: April 2017

Background Caloric restriction is associated with broad therapeutic potential in various diseases and an increase in health and life span. In this study, we assessed the impact of caloric restriction on acute and inflammatory nociception in mice, which were either fed ad libitum or subjected to caloric restriction with 80% of the daily average for two weeks. Results The behavioral tests revealed that inflammatory nociception in the formalin test and in zymosan-induced mechanical hypersensitivity were significantly decreased when mice underwent caloric restriction. As potential mediators of the diet-induced antinociception, we assessed genes typically induced by inflammatory stimuli, AMP-activated kinase, and the endocannabinoid system which have all already been associated with nociceptive responses. Zymosan-induced inflammatory markers such as COX-2, TNFα, IL-1β, and c-fos in the spinal cord were not altered by caloric restriction. In contrast, AMPKα2 knock-out mice showed significant differences in comparison to C57BL/6 mice and their respective wild type littermates by missing the antinociceptive effects after caloric restriction. Endocannabinoid levels of anandamide and 2-arachidonyl glyceroldetermined in serum by LC-MS/MS were not affected by either caloric restriction alone or in combination with zymosan treatment. However, cannabinoid receptor type 1 expression in the spinal cord, which was not altered by caloric restriction in control mice, was significantly increased after caloric restriction in zymosan-induced paw inflammation. Since increased cannabinoid receptor type 1 signaling might influence AMP-activated kinase activity, we analyzed effects of anandamide on AMP-activated kinase in cell culture and observed a significant activation of AMP-activated kinase. Thus, endocannabionoid-induced AMP-activated kinase activation might be involved in antinociceptive effects after caloric restriction. Conclusion Our data suggest that caloric restriction has an impact on inflammatory nociception which might involve AMP-activated kinase activation and an increased activity of the endogenous endocannabinoid system by caloric restriction-induced cannabinoid receptor type 1 upregulation.
Severe Hallux Valgus With Coalition of the Hallux Sesamoids Treated With Modified Lapidus Procedure: A Case Report
Authors: Kurashige Toshinori , Suzuki Seiichi 
Published: April 2017

Coalition of the hallux sesamoids is an extremely rare condition. To our knowledge, only 1 case report has been published. We report a case of severe hallux valgus deformities with coalitions of the hallux sesamoids. The coalitions themselves were asymptomatic; however, this severe hallux valgus deformity needed to be surgically treated. The hallux sesamoids in both feet appeared to be fused and heart shaped on anteroposterior radiographs and dumbbell shaped on axial radiographs. It is known that postoperative incomplete reduction of the medial sesamoids can be a risk factor for the recurrence of hallux valgus. The computed tomography scan demonstrated a groove in the bottom of the center of the heart-shaped sesamoid. The flexor hallucis longus tendon was located in the groove. Therefore, a modified Lapidus procedure was performed considering the medial half of the heart-shaped sesamoid as the medial sesamoid. Although delayed union occurred, successful correction of the deformity was achieved. Levels of Evidence: Level IV
Correlation of arterial blood gas markers and lactate levels with outcomes in pediatric traumatic brain injury
Authors: Ng Zhi Min , Hong Wei Jie , Chong Shu-Ling , Allen John C , Loh Lik Eng , Low David Chyi Yeu , Lee Jan Hau 
Published: April 2017

Background: Various physical markers have been used to predict outcome of traumatic brain injury in children. However, the utility of metabolic alterations for prognostication has been poorly described. Thus, we aim to correlate arterial blood gas markers and lactate levels with outcomes in children with moderate to severe traumatic brain injury. Methods: This is a retrospective cohort study that included all patients <16 years old who presented to the Emergency Department with moderate to severe traumatic brain injury (Glasgow Coma Scale ⩽13). Serial arterial blood gas results and lactate levels in the first five days of admission to a pediatric intensive care unit (PICU) were reviewed. Primary outcome was in-hospital mortality. Secondary outcomes were 28-day ventilator-free and PICU-free days. A stepwise logistic regression analysis in conjunction with receiver operating characteristic analysis were used to identify variables that were associated with in-hospital mortality. Secondary outcomes were analyzed using multiple linear regression. Results: Among the 43 patients analyzed, more than half of the patients (60%) had severe traumatic brain injury (Glasgow Coma Scale 8). Twenty-seven of the 43 (65%) patients underwent neurosurgical intervention and overall mortality was 9/43 (20.9%). The worst base excess and lactate levels of Day 2 of PICU stay were found to be most predictive for mortality with maximal area-under-curve (95% confidence interval) of 0.967 (0.906, 1.000). Worst lactate level on day 2 of PICU stay was also found to be associated with ventilator-free days and PICU-free days. Conclusion: In children with moderate to severe traumatic brain injury, base excess and lactate on Day 2 of PICU stay were predictors of mortality, duration of mechanical ventilation and length of PICU stay.
Increasing the Rate of Living Donor Kidney Transplantation in Ontario: Donor- and Recipient-Identified Barriers and Solutions
Authors: Getchell Leah E. , McKenzie Susan Q. , Sontrop Jessica M. , Hayward Jade S. , McCallum Megan K. , Garg Amit X. 
Published: April 2017

Purpose of Review: To hear from living kidney donors and recipients about what they perceive are the barriers to living donor kidney transplantation, and how patients can develop and lead innovative solutions to increase the rate and enhance the experiences of living donor kidney transplantation in Ontario. Sources of Information: A one-day patient-led workshop on March 10th, 2016 in Toronto, Ontario. Methods: Participants who were previously engaged in priority-setting exercises were invited to the meeting by patient lead, Sue McKenzie. This included primarily past kidney donors, kidney transplant recipients, as well as researchers, and representatives from renal and transplant health care organizations across Ontario. Key Findings: Four main barriers were identified: lack of education for patients and families, lack of public awareness about living donor kidney transplantation, financial costs incurred by donors, and health care system-level inefficiencies. Several novel solutions were proposed, including the development of a peer network to support and educate patients and families with kidney failure to pursue living donor kidney transplantation; consistent reimbursement policies to cover donors’ out-of-pocket expenses; and partnering with the paramedical and insurance industry to improve the efficiency of the donor and recipient evaluation process. Limitations: While there was a diversity of experience in the room from both donors and recipients, it does not provide a complete picture of the living kidney donation process for all Ontario donors and recipients. The discussion was provincially focused, and as such, some of the solutions suggested may already be in practice or unfeasible in other provinces. Implications: The creation of a patient-led provincial council was suggested as an important next step to advance the development and implementation of solutions to overcome patient-identified barriers to living donor kidney transplantation.
Sustainability of treatment effect of a 3-year early intervention programme for first-episode psychosis
Authors: Chang Wing Chung , Yan Kwong Vivian Wing , Lau Emily Sin Kei , So Hon Cheong , Wong Corine Sau Man , Chan Gloria Hoi Kei , Jim Olivia Tsz Ting , Hui Christy Lai Ming , Chan Sherry Kit Wa , Lee Edwin Ho Ming , Chen Eric Yu Hai 
Published: April 2017

BackgroundEvidence indicates that the positive effects of 2-year early intervention services for psychosis are not maintained after service withdrawal. Optimal duration of early intervention in sustaining initial improved outcomes remains to be determined.AimsTo examine the sustainability of the positive effects of an extended, 3-year, early intervention programme for patients with first-episode psychosis (FEP) after transition to standard care.MethodA total of 160 patients, who had received a 2-year early intervention programme for FEP, were enrolled to a 12-month randomised-controlled trial (ClinicalTrials.gov: NCT01202357) comparing a 1-year extension of the early intervention (3-year specialised treatment) with step-down care (2-year specialised treatment). Participants were followed up and reassessed 2 and 3 years after inclusion to the trial.ResultsThere were no significant differences between the treatment groups in outcomes on functioning, symptom severity and service use during the post-trial follow-up period.ConclusionsThe therapeutic benefits achieved by the extended, 3-year early intervention were not sustainable after termination of the specialised service.