bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-controlled hospital admission for patients with severe mental disorders: study protocol for a nationwide prospective multicentre study
Authors: Thomsen Christoffer Torgaard , Benros Michael Eriksen , Hastrup Lene Halling , Andersen Per Kragh , Giacco Domenico , Nordentoft Merete 
Published: September 2016

IntroductionPatient-controlled hospital admission for individuals with severe mental disorders is a novel approach in mental healthcare. Patients can admit themselves to a hospital unit for a short stay without being assessed by a psychiatrist or contacting the emergency department. Previous studies assessing the outcomes of patient-controlled hospital admission found trends towards reduction in the use of coercive measures and length of hospital stay; however, these studies have methodological shortcomings and small sample sizes. Larger studies are needed to estimate the effect of patient-controlled hospital admission on the use of coercion and of healthcare services.Design and methodsWe aim to recruit at least 315 patients who are offered a contract for patient-controlled hospital admissions in eight different hospitals in Denmark. Patients will be followed-up for at least 1 year to compare the use of coercive measures and of healthcare services, the use of medications and suicidal behaviour. Descriptive statistics will be used to investigate hospitalisations, global assessment of functioning (GAF) and patient satisfaction with treatment. To minimise selection bias, we will match individuals using patient-controlled hospital admission and controls with a 1:5 ratio via a propensity score based on the following factors: sex, age group, primary diagnosis, substance abuse as secondary diagnosis, coercion, number of psychiatric bed days, psychiatric history, urbanity and suicidal behaviour. Additionally, a historical control study will be undertaken in which patients serve as their own control group prior to index date.Ethics and disseminationThe study has been approved by The Danish Health and Medicines Authority (j.nr.: 3-3013-934/1/) and by The Danish Data Protection Agency (j.nr.: 2012-58-0004). The study was categorised as a register study by The Danish Health Research Ethics Committee and therefore no further approval was needed (j.nr.: H-2-2014-FSP70). Findings will be disseminated through scientific publications, presentations and in a PhD thesis.
Unsupervised Bug Report Categorization Using Clustering and Labeling Algorithm
Authors: Limsettho Nachai , Hata Hideaki , Monden Akito , Matsumoto Kenichi 
Published: September 2016

Bug reports are one of the most crucial information sources for software engineering offering answers to many questions. Yet, getting these answers is not always easy; the information in bug reports is often implicit and some processes are required to extract the meaning of these reports. Most research in this area employ a supervised learning approach to classify bug reports so that required types of reports could be identified. However, this approach often requires an immense amount of time and effort, the resources that already too scarce in many projects. We aim to develop an automated framework that can categorize bug reports, according to their grammatical structure without the need for labeled data. Our framework categorizes bug reports according to their text similarity using topic modeling and a clustering algorithm. Each group of bug reports are labeled with our new clustering labeling algorithm specifically made for clusters in the topic space. Our framework is highly customizable with a modular approach and options to incorporate available background knowledge to improve its performance, while our cluster labeling approach make use of natural language process (NLP) chunking to create the representative labels. Our experiment results demonstrate that the performance of our unsupervised framework is comparable to a supervised learning one. We also show that our labeling process is capable of labeling each cluster with phrases that are representative for that cluster's characteristics. Our framework can be used to automatically categorize the incoming bug reports without any prior knowledge, as an automated labeling suggestion system or as a tool for obtaining knowledge about the structure of the bug report repository.
Irreducibility Properties of Keller Maps
Authors: de Bondt Michiel , Yan Dan 
Published: September 2016

Jędrzejewicz showed that a polynomial map over a field of characteristic zero is invertible, if and only if the corresponding endomorphism maps irreducible polynomials to irreducible polynomials. Furthermore, he showed that a polynomial map over a field of characteristic zero is a Keller map, if and only if the corresponding endomorphism maps irreducible polynomials to square-free polynomials. We show that the latter endomorphism maps other square-free polynomials to square-free polynomials as well. In connection with the above classification of invertible polynomial maps and the Jacobian Conjecture, we study irreducibility properties of several types of Keller maps, to each of which the Jacobian Conjecture can be reduced. Herewith, we generalize the result of Bakalarski that the components of cubic homogeneous Keller maps with a symmetric Jacobian matrix (over ℂ and hence any field of characteristic zero) are irreducible. Furthermore, we show that the Jacobian Conjecture can even be reduced to any of these types with the extra condition that each affinely linear combination of the components of the polynomial map is irreducible. This is somewhat similar to reducing the planar Jacobian Conjecture to the so-called (planar) weak Jacobian Conjecture by Kaliman.
3D geological models to groundwater flow models: data integration between GSI3D and groundwater flow modelling software GMS and FeFlow®
Authors: Pasanen A. H. , Okkonen J. S. 
Published: September 2016

Abstract
Data integration between different software is routinely needed in order to create suitable data formats or necessary data manipulation prior to importing the data. The procedures and workflows are not usually published. This paper presents the data integration between GSI3D (Geological Surveying and Investigation in 3 Dimensions) and groundwater flow modelling software GMS version 7.0 (Groundwater Modelling Systems) and FeFlow®. Geological models for two sites in Finland, an esker aquifer at Patamäki and a mine site in Luikonlahti, were constructed using dedicated 3D geological modelling software GSI3D.
The data from the GSI3D model in Patamäki was exported as ASCII grid files directly to GMS in order to delineate hydrogeological features prior to groundwater flow modelling. The data from the GSI3D model in Luikonlahti was first manipulated in ArcGIS to make it amenable in FeFlow®.
In both modelling locations, the detailed geological modelling greatly helped to discern different hydraulic conductivity zones that are based on different geological materials. This, in addition, eases the development of conceptual groundwater flow models, the model calibration process and potentially improves the simulation results.
Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis
Authors: Xia Tianli , Konno Hiroyasu , Barber Glen N. 
Published: September 2016

Abstract
The innate immunoregulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells to stimulate antitumor T-cell immunity. Here, we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically, STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase, which generates STING-activating cyclic dinucleotides after binding cytosolic DNA species. Loss of STING function rendered melanoma cells unable to produce type I IFN and other immune cytokines after exposure to cytosolic DNA species. Consequently, such cells were highly susceptible to infection with DNA viruses including HSV1, a variant of which is being developed presently as a therapeutic oncolytic virus [talimogene laherparepvec (T-VEC)]. Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. Cancer Res; 76(22); 6747–59. ©2016 AACR.
Oral Bisphosphonates and Improved Survival of Breast Cancer
Authors: Rennert Gad , Pinchev Mila , Gronich Naomi , Saliba Walid , Flugelman Anath , Lavi Idit , Goldberg Hadassah , Fried Georgeta , Steiner Mariana , Bitterman Arie , Landsman Keren , Rennert Hedy S. 
Published: September 2016

Abstract
Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.
Experimental Design: A nested case–control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.
Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41–0.96, P = 0.03; breast cancer–specific survival: OR = 0.28, 0.09–0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.
Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684–9. ©2016 AACR.
Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma
Authors: Wu Licun , Allo Ghassan , John Thomas , Li Ming , Tagawa Tetsuzo , Opitz Isabelle , Anraku Masaki , Yun Zhihong , Pintilie Melania , Pitcher Bethany , Liu Geoffrey , Feld Ron , Johnston Michael R. , de Perrot Marc , Tsao Ming-Sound 
Published: September 2016

Abstract
Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor–stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.
Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.
Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1–5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.
Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies. Clin Cancer Res; 23(4); 1060–7. ©2016 AACR.
A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer
Authors: McKay Rana R. , Werner Lillian , Mostaghel Elahe A. , Lis Rosina , Voznesensky Olga , Zhang Zhenwei , Marck Brett T. , Matsumoto Alvin M. , Domachevsky Liran , Zukotynski Katherine A. , Bhasin Manoj , Bubley Glenn J. , Montgomery Bruce , Kantoff Philip W. , Balk Steven P. , Taplin Mary-Ellen 
Published: September 2016

Abstract
Purpose: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride.
Experimental Design: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5 mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression.
Results: Forty patients were enrolled. Sixty percent (n = 24) achieved a ≥50% reduction in prostate-specific antigen (PSA). The median time to radiographic progression was 11 months. Nearly all baseline (n = 29 of 31) and posttreatment (n = 16 of 16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n = 10 of 21) of baseline and 42% (n = 5 of 12) of treatment discontinuation specimens. Compared with patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens.
Conclusions: Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The noncomparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches toward AR inhibition. Clin Cancer Res; 23(4); 935–45. ©2016 AACR.
Anti-PD1–Induced Pneumonitis: Capturing the Hidden Enemy
Authors: Castanon Eduardo 
Published: September 2016

Abstract
Anti-PD1 antibodies have led to a therapeutic shift in cancer treatment. Although classically described as "well tolerated," these drugs can lead to severe immune-related adverse events. Using CT scan imaging, Nishino and colleagues describe different radiologic patterns and their possible relation to severity of several cases of anti-PD1–induced pneumonitis. Clin Cancer Res; 22(24); 5956–8. ©2016 AACR.
See related article by Nishino et al., p. 6051
Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy
Authors: Johanns Tanner M. , Miller Christopher A. , Dorward Ian G. , Tsien Christina , Chang Edward , Perry Arie , Uppaluri Ravindra , Ferguson Cole , Schmidt Robert E. , Dahiya Sonika , Ansstas George , Mardis Elaine R. , Dunn Gavin P. 
Published: September 2016

Abstract
We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy.
Significance: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. Cancer Discov; 6(11); 1230–6. ©2016 AACR.
See related commentary by Snyder and Wolchok, p. 1210.
This article is highlighted in the In This Issue feature, p. 1197
Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment
Authors: Massimi Isabella , Lotti Lavinia , Temperilli Flavia , Mancone Massimo , Sardella Gennaro , Calcagno Simone , Turriziani Ombretta , Frati Luigi , Pulcinelli Fabio M. 
Published: September 2016

SummaryPlatelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1–independent mechanism.
Combination therapy for inhibitor reversal in haemophilia A using monoclonal anti-CD20 and rapamycin
Authors: Sherman Alexandra , Byrne Barry J. , Markusic David M. , Jiang Haiyan , Biswas Moanaro , Rogers Geoffrey L. , Herzog Roland W. 
Published: September 2016

SummaryDevelopment of antibodies (inhibitors) against coagulation factor VIII (FVIII) is a major complication of intravenous replacement therapy in haemophilia A (HA). Current immune tolerance induction (ITI) regimens are not universally effective. Rituximab, a B cell-depleting antibody against CD20, has shown mixed results for inhibitor reversal in patients. This study aims to develop a combinatorial therapy for inhibitor reversal in HA, using anti-murine CD20 (anti-mCD20) antibody and rapamycin, which targets both B and T cell responses. Additionally, it extensively characterises the role of the IgG backbone in B cell depletion by anti-CD20 antibodies. For this, inhibitors were generated in BALB/c-HA mice by weekly IV injection of FVIII. Subsequently, anti-mCD20 (18B12) with IgG2a or IgG1 backbone was injected IV in two doses three weeks apart and B cell depletion and recovery was characterised. Rapamycin was administered orally 3x/week (for 1 month) while continuing FVIII injections. Altering the IgG backbone of anti-mCD20 from IgG2a to IgG1 reduced overall depletion of B cells (including memory B cells), and marginal zone, B-10, and B-1b cells were specifically unaffected. While neither antibody was effective alone, in combination with rapamycin, anti-mCD20 IgG2a but not IgG1 was able to reverse inhibitors in HA mice. This regimen was particularly effective for starting titres of ∼10 BU. Although IgG1 anti-mCD20 spared potentially tolerogenic B cell subsets, IgG2a directed sustained hyporesponsiveness when administered in conjunction with rapamycin. This regimen represents a promising treatment for inhibitor reversal in HA, as both of these compounds have been extensively used in human patients.Supplementary Material to this article is available at www.thrombosis-online.com.
A novel platelet-type von Willebrand disease mutation (GP1BA p.Met255Ile) associated with type 2B “Malmö/New York” von Willebrand disease
Authors: Lavenu-Bombled Cécile , Guitton Corinne , Dupuis Arnaud , Baas Marie-Jeanne , Desconclois Céline , Dreyfus Marie , Li Renhao , Caron Claudine , Gachet Christian , Fressinaud Edith , Lanza François 
Published: September 2016

SummaryInteraction between von Willebrand factor (VWF) and platelet GPIbα is required for primary haemostasis. Lack or loss-of-function in the ligand-receptor pair results in bleeding complications. Paradoxically, gain-of-function mutations in VWF or GPIbα also result in bleeding complications as observed in type 2B von Willebrand disease (VWD) and platelet-type- (PT-) VWD, respectively. A similar phenotype is observed with increased ristocetin-induced platelet agglutination and disappearance of the highest molecular weight multimers of VWF. We evaluated a patient with a bleeding disorder and a biological presentation compatible with type 2B VWD. VWF and platelet functional assays, sequencing of the VWF and GP1BA genes, and expression studies in HEK cells were performed. Sequencing of the VWF gene in the propositus revealed a heterozygous p.Pro1266Leu mutation previously found in type 2B VWD Malmö/New York. These variants are characterised by a mild phenotype and a normal VWF multimer composition suggesting the presence of a second mutation in our propositus. Sequencing of the GP1BA gene revealed a heterozygous c.765G>A substitution changing Met at position 255 of GPIbα to Ile. This new mutation is located in the β-switch domain where five other gain-of-function mutations have been reported in PT-VWD. Expression of GPIbα Ile255 in HEK GPIb-IX cells resulted in enhanced VWF binding compared to wild-type, similar to known PT-VWD mutations (p.Val249, p.Ser249 and p.Val255) indicating that it contributes to the propositus defects. This first report associating PT-with type 2B VWD illustrates the importance of combining biological assays with genetic testing to better understand the clinical phenotype.