bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas.
Authors: Conroy Thierry , Hammel Pascal , Hebbar Mohamed , Ben Abdelghani Meher , Wei Alice Chia-chi , Raoul Jean-Luc , Chone Laurence , Francois Eric , Artru Pascal , Biagi James Joseph , Lecomte Thierry , Assenat Eric , Faroux Roger , Ychou Marc , Volet Julien , Sauvanet Alain , Jouffroy-Zeller Claire , RAT Patrick , Castan Florence , Bachet Jean-Baptiste 
Published: June 2018

LBA4001 Background: FOLFIRINOX is more effective than gem as first-line treatment in metastatic pancreatic cancer for patients (pts) with good performance status. This trial assessed the benefit of mFOLFIRINOX in the adjuvant setting. Methods: PRODIGE 24/CCTG PA.6 is a phase III multicenter, randomized clinical trial. Pts aged 18-79 years with histologically proven pancreatic ductal adenocarcinomas, 21-84 days after R0 or R1 resection, WHO PS ≤1, adequate hematologic and renal function, and no cardiac ischemia, were eligible. Randomization was stratified by center, pN, R margin status, and post-operative CA 19-9 level (≤ 90 U/mL vs 91-180). Arm A pts received 28-day cycles of gem on days 1, 8, and 15 for 6 cycles. Arm B pts received mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) every 14 days for 12 cycles. Primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), metastasis-free survival (MFS), and adverse events (AE). 490 pts were required to observe 342 events to show a gain in 3-year DFS from 17% to 27% (HR = 0.74) with a two-sided α = 0.05 and 80% power. Hazard ratios (HR) and 95% CI were estimated by a stratified Cox proportional hazard model. We observed 91.5% of the events required. The IDMC approved early ITT analysis before March 15, 2018. Surgical procedures, pathology and postoperative CT scans reports were centrally reviewed. Results: From Apr 2012 to Oct 2016, 493 pts were enrolled in 77 centers: Arm A/B: 246/247. With a median follow up of 30.5 months [m] (95% CI, 29.5-33.7), median DFS was 12.8 (95% CI, 11.7-15.2) in Arm A vs 21.6 m (95% CI, 17.5-26.7) in Arm B, HR = 0.59 (95% CI, 0.47-0.74). The median OS (Arm A/B) was 34.8 (95% CI, 28.6-43.8) vs 54.4 m (95% CI, 41.5- --), HR = 0.66 (95% CI, 0.49-0.89). The median MFS (Arm A/B) was 17.7 (95% CI, 14.2-21.7) vs 30.4 m (95% CI, 21.6- --), HR = 0.59 (95% CI, 0.46-0.76). Grade 3-4 AE (Arm A/B) were reported in 51.1% vs 75.5%, including 12% grade 4 in each arm, with a toxic death in Arm A. Conclusion: Adjuvant mFOLFIRINOX is safe and significantly improves DFS, MFS and OS compared to gem. Clinical trial information: NCT01526135.
Abi Race: A prospective, multicenter study of black (B) and white (W) patients (pts) with metastatic castrate resistant prostate cancer (mCRPC) treated with abiraterone acetate and prednisone (AAP).
Authors: George Daniel J. , Heath Elisabeth I. , Sartor A. Oliver , Sonpavde Guru , Berry William R. , Healy Patrick , Winters Carolyn , Riggan Colleen , Anand Monika , Kephart Julie , Milowsky Matthew I. , Fleming Mark T. , Balaji K. C. , Zhang Tian , Bitting Rhonda L. , Harrison Michael Roger , McNamara Megan Ann , Freedman Jennifer A. , Halabi Susan , Armstrong Andrew J. , Bruner Deborah 
Published: June 2018

LBA5009 Background: Pivotal trials of AAP for patients with mCRPC enrolled few B pts, a population with a higher mortality from prostate cancer. Retrospective data suggests B pts may have higher PSA response rates than W pts treated with AAP for mCRPC. Therefore, we prospectively investigated AAP in B vs. W pts with mCRPC. Methods: Abi Race (NCT01940276) is a prospective, multicenter, parallel group study of AP in 100 men (50 B, 50 W) with mCRPC, self-identified by race. All pts received AA 1000 mg/D and P 10 mg/D (AAP) until disease progression or unacceptable adverse events (AE). The primary objective was radiographic progression-free survival (rPFS); key secondary endpoints include PSA kinetics and safety. Exploratory analyses include SNP, metabolomics and hormonal differences by race. Results: Baseline characteristics among pts were similar. The median rPFS for B and W pts was 16.8 months (mo) in each. However, PSA PFS varied by race; median PSA PFS for B and W pts were 16.6 and 11.5 mo [Table]. B pts also had numerically higher rates of ≥30%, ≥50% and ≥90% PSA decline [Table]. AEs were similar in frequency and severity by race including hypertension (42 vs 40%); however, fatigue was higher in W pts (40 vs 26%), and hypokalemia was higher in B pts (36 vs 18%). SNP profiling revealed differences in key genes involved in androgen metabolism and transport. Conclusions: This is the first prospective multicenter study by race of secondary hormonal therapy in mCRPC. B pts may have greater and more durable PSA response to AAP than W pts. SNP patterns vary by race and will be evaluated for prognostic significance. Further prospective studies in B pts are possible and needed to understand the impact of racial determinants on outcome of new hormonal regimens. Clinical trial information: NCT01940276. [Table: see text]
Are women with head and neck cancer undertreated?
Authors: Park Annie , Albaster Amy , Shen Hanjie , Mell Loren K. , Katzel Jed Abraham 
Published: June 2018

LBA6002 Background: Generalized competing event (GCE) models have been used to stratify patients with cancer according to their relative hazard for cancer death versus death from other causes. We evaluated outcomes for head and neck cancer (HNC) patients treated at Kaiser Permanente Northern California (KPNC) based on demographic data and comorbidities using a GCE model. Methods: We identified 884 HNC patients diagnosed 2000-2015 from the KPNC cancer registry, age 18-85 and stage II-IVB by AJCC 7th edition. Using the GCE proportional relative hazards model, controlling for age, sex, tumor site, and Charlson comorbidity index (CCI), we identified associations between these factors and the relative hazard for HNC-specific mortality (ω+ ratio, ‘gcerisk’ package in R). Death, disenrollment, and end of study (12/31/2016) were used as censoring events. Logistic regression models estimated the odds of receiving intensive treatment (platinum based regimen), adjusting for the same covariates plus stage, smoking, and alcohol abuse history. Results: With a median follow-up of 2.9 years, 271 patients died of cancer, and 93 of non-cancer causes. Compared to male, females were less likely to receive intensive chemotherapy (35% vs. 46%, p = 0.006) and radiation (60% vs. 70%, p = 0.008). On GCE analysis, female patients had an increased relative hazard ratio (RHR) for death from HNC vs. other causes (adjusted RHR 1.92; 95% CI 1.07-3.43), indicating they may be relatively undertreated. Conclusions: Female patients in our cohort may be undertreated in clinical practice, potentially missing the opportunity to aggressively treat their HNC. This study supports the use of a GCE methodology to objectively identify patients more likely to benefit from treatment intensification. These findings may help guide future research in health disparities.[Table: see text]
Unsuitable for Children? Adult-erated Age in Underground Graphic Narratives
Authors: Howard Yetta 
Published: June 2018

Abstract
This article explores expressions of eroto-abject desire in two collaborative graphic narratives: Kathy Acker, Diane DiMassa, and Freddie Baer’s Pussycat Fever (1995) and David Wojnarowicz, James Romberger, and Marguerite Van Cook’s 7 Miles a Second (1996). Reflecting the resistance to heteronormative logics of age categorization, “adult-erated age” names the ways that childhoods in the texts are adult oriented but also characterizes how they, in their respective contexts, revise and reflect notions of impurity and being worsened as singularly queer ways of being and representing. This is accomplished by turning to traumatic memory and ill embodiment via graphic textual form.
Continuous positive airway pressure plus low flow oxygen versus usual care of severe acute cardiogenic pulmonary edema in the pre-hospital setting: A randomised controlled trial
Authors: Austin Michael A. , Wills Karen , Kilpatrick David , Walters E. Haydn 
Published: June 2018

Background: Acute cardiogenic pulmonary edema (ACPE) is characterized by acute breathlessness and hypoxia and is associated with poor prognosis. Standard pre-hospital management of ACPE includes high-flow oxygen, nitroglycerin and, in severe cases, assisted ventilation. Patients with ACPE can be supported with newer modalities of non-invasive ventilation, specifically continuous positive airway pressure (CPAP). The aim of this study was to determine whether patients with ACPE treated with CPAP plus low-flow oxygen pre-hospitally have a lower mortality rate than those treated conventionally. Methods: This study was a pre-hospital randomised, non-blinded controlled trial conducted July 2009–July 2010. Included were all participants transported by ambulance and admitted to the Royal Hobart Hospital, Tasmania, Australia. The study population was consecutive persons ≥18 years of age with sudden onset of severe respiratory distress, diagnosed as ACPE. Patients were included if they required ventilatory assistance. Patients required a GCS >12 and blood pressure >90 mmHg systolic to safely receive CPAP. The primary outcome was pre- or in-hospital mortality. Results: In total, 50 patients were enrolled with mean age of 79.8 (±11.9) years. There were two deaths (8.3%) in the CPAP arm and nine (34.6%) in the control arm (RR, −0.24; 95% CI, 0.06–1.00; p=0.051) with a number needed to treat of 4. CPAP plus low-flow oxygen was significantly less likely to result in respiratory acidosis (mean difference in pH, −0.11; 95% CI, −0.04–−0.17; p=0.002), with elevated pCO2 (mean difference, −10.0 mmHg; 95% CI, −19.2–−0.78; p=0.026). The length of hospital stay was significantly shorter in the surviving patients who received CPAP (ratio of means, 0.45; 95% CI, 0.29–0.70; p≤0.001). Discussion: This study, which provides interim results due to early termination of the trial, shows CPAP in the pre-hospital setting for ACPE is practicable and is associated with improved patient outcomes.
Revision total hip arthroplasty using the Kerboull acetabular reinforcement device for Paprosky type III defects involving the inferior margin of the acetabulum
Authors: Gibon E. , Barut N. , Courpied J-P. , Hamadouche M. 
Published: June 2018

Aims The purpose of this retrospective study was to evaluate the minimum five-year outcome of revision total hip arthroplasty (THA) using the Kerboull acetabular reinforcement device (KARD) in patients with Paprosky type III acetabular defects and destruction of the inferior margin of the acetabulum. Patients and Methods We identified 36 patients (37 hips) who underwent revision THA under these circumstances using the KARD, fresh frozen allograft femoral heads, and reconstruction of the inferior margin of the acetabulum. The Merle d’Aubigné system was used for clinical assessment. Serial anteroposterior pelvic radiographs were used to assess migration of the acetabular component. Results At a mean follow-up of 8.2 years (5 to 19.3), the mean Merle d’Aubigné score increased from 12.5 (5 to 18) preoperatively to 16.5 (10 to 18) (p < 0.0001). The survival rate at ten years was 95.3% (sd 4.5; 95% confidence interval (CI) 86.4 to 100) and 76.5% (sd 9.9, 95% CI 57.0 to 95.9) using aseptic loosening and radiological loosening as the endpoints, respectively. Conclusion These results show that the use of the KARD with reconstruction of the inferior margin of the acetabulum in revision THA is associated with acceptable clinical results and survival at mid-term follow-up with, however, a high rate of migration of the acetabular component of 21.6%. Cite this article: Bone Joint J 2018;100-B:725–32.
Alpha-defensin and the Synovasure lateral flow device for the diagnosis of prosthetic joint infection
Authors: Marson B. A. , Deshmukh S. R. , Grindlay D. J. C. , Scammell B. E. 
Published: June 2018

Aims The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI). Materials and Methods Studies using alpha-defensin or Synovasure (Zimmer Biomet, Warsaw, Indiana) to diagnose PJI were identified from systematic searches of electronic databases. The quality of the studies was evaluated using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) tool. Meta-analysis was completed using a bivariate model. Results A total of 11 eligible studies were included. The median QUADAS score was 13 (interquartile range 13 to 13) out of 14. Significant conflicts of interest were identified in five studies. The pooled sensitivity for the laboratory alpha-defensin test was 0.95 (95% confidence interval (CI) 0.91 to 0.98) and the pooled specificity was 0.97 (95% CI 0.95 to 0.98) for four studies with a threshold level of 5.2 mgl-1 The pooled sensitivity for the lateral flow cassette test was 0.85 (95% CI 0.74 to 0.92) and the pooled specificity was 0.90 (95% CI 0.91 to 0.98). There was a statistically significant difference in sensitivity (p = 0.019), but not specificity (p = 0.47). Conclusion Laboratory-based alpha-defensin testing remains a promising tool for diagnosing PJI. The lateral flow cassette has a significantly lower performance and pooled results are comparable to the leucocyte esterase test. Further studies are required before the widespread adoption of the lateral flow cassette alpha-defensin test. Cite this article: Bone Joint J 2018;100-B:703–11.
The forkhead domain hinge-loop plays a pivotal role in DNA binding and transcriptional activity of FOXP2
Authors: Morris Gavin , Stoychev Stoyan , Naicker Previn , Dirr Heini W. , Fanucchi Sylvia 
Published: June 2018

Abstract
Forkhead box (FOX) proteins are a ubiquitously expressed family of transcription factors that regulate the development and differentiation of a wide range of tissues in animals. The FOXP subfamily members are the only known FOX proteins capable of forming domain-swapped forkhead domain (FHD) dimers. This is proposed to be due to an evolutionary mutation (P539A) that lies in the FHD hinge loop, a key region thought to fine-tune DNA sequence specificity in the FOX transcription factors. Considering the importance of the hinge loop in both the dimerisation mechanism of the FOXP FHD and its role in tuning DNA binding, a detailed investigation into the implications of mutations within this region could provide important insight into the evolution of the FOX family. Isothermal titration calorimetry and hydrogen exchange mass spectroscopy were used to study the thermodynamic binding signature and changes in backbone dynamics of FOXP2 FHD DNA binding. Dual luciferase reporter assays were performed to study the effect that the hinge-loop mutation has on FOXP2 transcriptional activity in vivo. We demonstrate that the change in dynamics of the hinge-loop region of FOXP2 alters the energetics and mechanism of DNA binding highlighting the critical role of hinge loop mutations in regulating DNA binding characteristics of the FOX proteins.
Resolving abstract anaphors in Spanish discourse: Underspecification and mereological structures
Authors: Zulaica Hernández Iker 
Published: June 2018

Abstract
Anaphoric underspecification involves multiple potential candidate antecedents for an anaphoric expression. In abstract object anaphora, where linguistic antecedents are clauses, sentences and larger fragments of discourse, the source of referential underspecification is commonly found at the propositional level. Thus, underspecified abstract anaphors have multiple antecedents of a higher-order nature (i.e., propositions and events). Following previous research on anaphoric underspecification with nominal antecedents, I propose a hypothetical three-step process toward the resolution of underspecified abstract object anaphors by hearers in discourse: (i) creation of a complex abstract object with a mereological structure that includes all potential interpretations for an anaphor, (ii) recognition of the thematic connection among propositions intended by the speaker in the form of a specific rhetorical relation, and 3) resolution of the abstract anaphor. Potential antecedents for any underspecified abstract anaphor may include atomic propositions and complex abstract referents that result from a merged interpretation of several propositions that are thematically connected. Provided that it is available, I claim that such a merged interpretation, which is part of the mereological structure, is the preferred interpretation as it is generally interpreted as part of a general purpose by the speaker, in addition to contributing to the thematic coherence of discourse.
Meaning change in Chinese: A numeral phrase construction from adjectives to superlatives to definite descriptions
Authors: Jin Dawei , Chen Jun 
Published: June 2018

AbstractThis paper analyzes a hitherto unnoticed semantic change process in Chinese, in which lexical (adjectival) materials develop into superlative operators, and subsequently turn into definiteness markers. Our analysis focuses on the semantic factors that underlie this meaning change trajectory. Specifically, we argue that frequent association of gradable adjectives with superlative implication leads to pragmatic strengthening in which the superlative implication conventionally enters the literal meaning. Furthermore, we show that a further change in the extension of the nominal part of superlative phrases leads to a maximality reanalysis that is compatible with the semantics of definite NPs. This paper contributes to the burgeoning field of applying truth-conditional semantics to theories of grammaticalization.
Stiffness control of a nonlinear mechanical folded beam for wideband vibration energy harvesters
Authors: Amri Mohamed , Basset Philippe , Galayko Dimitri , Cottone Francesco , Halvorsen Einar , Nguyen S. Duy , Najar Fehmi , Bourouina Tarik 
Published: June 2018

Abstract
This paper presents a novel approach to design and optimize geometric nonlinear springs for wideband vibration energy harvesting. To this end, we designed a spring with several folds to increase its geometric nonlinearities. A numerical analysis is performed using the Finite Element Method to estimate its quadratic and cubic spring stiffness. A nonlinear effective spring constant is then calculated for different values of the main folding angle. We demonstrate that this angle can increase nonlinearities within the structure resulting in higher bandwidths, and that it is possible to control the behavior of the system to have softening-type or hardening-type response depending on the choice of the folding angle. Based on the Lindstedt-Poincaré perturbation technique, a first order approximation is determined to predict the frequency-response of the system. In order to validate the perturbation analysis, numerical solutions based on long-time integration method and mixed VHDL-AMS/Spice simulations are presented. Finally, this method is applied to a previously published device and shows a good agreement with experiments.
A Comparison of the National Football League's Annual National Football League Combine 1999–2000 to 2015–2016
Authors: Fitzgerald Corey F. , Jensen Randall L. 
Published: June 2018

Abstract
Fitzgerald, CF and Jensen, RL. A Comparison of the National Football League's annual National Football League combine 1999–2000 to 2015–2016. J Strength Cond Res 34(3): 771–781, 2020—The purpose of this study was to determine if elite football players are becoming bigger, faster, and stronger over the past decade by analyzing individual performances at the National Football League's (NFL) Combine. This study was conducted with (N = 1,263) subjects from the 1999–2000 (99–00) NFL Combines (n = 635) and the 2015–2016 (15–16) NFL Combines (n = 628) separated by position. Data were collected for height, body mass, 40-yd (36.58 m) dash, NFL 225 lb. (102.06 kg) repetitions test, vertical jump (VJ), broad jump (BJ), pro-agility shuttle, and 3-cone drill. Statistical significance between the years for all subjects participating in the NFL Combine was found for the 40-yd dash (99–00: mean ± SD = 4.85 ± 3.2; 15–16: 4.80 ± 3.5; p = 0.002) and VJ (99–00 = 82.04 ± 10.36 and 83.46 ± 10.59; p = 0.028) at the alpha p < 0.05 level. Statistical significance was also found for BJ (99–00 = 111.37 ± 8.81; 15–16: 115.03 ± 9.22; p < 0.001) and the 3-cone drill (99–00 = 7.41 ± 0.42; 15–16: 7.29 ± 4.1; p < 0.001) at the alpha p < 0.001 level. There were no statistically significant findings (p > 0.05) for mass or height found across all subjects by combine years. Results indicate that elite football players have improved their performance, when comparing results from 1999–2000 to 2015–2016. These finding may be beneficial to NFL franchises in their prospective player assessments.
Künstliche Intelligenz und Wettbewerbsrecht
Authors: Hennemann Moritz 
Published: June 2018

Zusammenfassung
Die disruptiven Technologien Künstlicher Intelligenz und die damit verbundenen Algorithmus-gestützten Anwendungen werden in nicht allzu ferner Zukunft den Wettbewerb sowohl um Märkte als auch auf ganz unterschiedlichen Märkten prägen. Folgerichtig erfährt die wettbewerbsrechtliche Erfassung und Beurteilung des Einsatzes von Algorithmen zunehmende Aufmerksamkeit im Schrifttum sowie in der Spruchpraxis von Behörden und Gerichten. Die darüber hinausreichende grundsätzliche(re) Befassung mit den übergeordneten Fragen von Künstlicher Intelligenz im Wettbewerbsrecht steht dagegen erst am Anfang. Vor diesem Hintergrund bestimmt und analysiert der nachfolgende Beitrag die kartellrechtlichen Rahmungen für Künstliche Intelligenz. Aufgeworfen sind insoweit grundlegende Fragestellungen zu den relevanten Märkten, zu Marktbeherrschung und Marktmachtmissbrauch, Kartellverbot und Fusionskontrolle sowie zu Verantwortlichkeit und Zurechnung im Wettbewerbsrecht de lege lata und de lege ferenda.