bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention
Authors: Lowery Maeve A. , Ptashkin Ryan , Jordan Emmet , Berger Michael F. , Zehir Ahmet , Capanu Marinela , Kemeny Nancy E. , O'Reilly Eileen M. , El-Dika Imane , Jarnagin William R. , Harding James J. , D'Angelica Michael I. , Cercek Andrea , Hechtman Jaclyn F. , Solit David B. , Schultz Nikolaus , Hyman David M. , Klimstra David S. , Saltz Leonard B. , Abou-Alfa Ghassan K. 
Published: May 2018

Abstract
Purpose: Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response.
Experimental Design: Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.
Results: A total of 195 patients were studied: 78% intrahepatic and 22% extrahepatic cholangiocarcinoma. The most commonly altered genes in intrahepatic cholangiocarcinoma were IDH1 (30%), ARID1A (23%), BAP1 (20%), TP53 (20%), and FGFR2 gene fusions (14%). A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including TP53:IDH1, IDH1:KRAS, TP53:BAP1, and IDH1:FGFR2. Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease. Genetic alterations with potential therapeutic implications were identified in 47% of patients, leading to biomarker-directed therapy or clinical trial enrollment in 16% of patients.
Conclusions: Cholangiocarcinoma is a genetically diverse cancer. Alterations in CDKN2A/B and ERBB2 are associated with negative prognostic implications in patients with advanced disease. Somatic alterations with therapeutic implications were identified in almost half of patients. These prospective data provide a contemporary benchmark for guiding the development of targeted therapies in molecularly profiled cholangiocarcinoma, and support to the use of molecular profiling to guide therapy selection in patients with advanced biliary cancers. Clin Cancer Res; 24(17); 4154–61. ©2018 AACR.
Phase I Trials of Anti-ENPP3 Antibody–Drug Conjugates in Advanced Refractory Renal Cell Carcinomas
Authors: Thompson John A. , Motzer Robert J. , Molina Ana M. , Choueiri Toni K. , Heath Elisabeth I. , Redman Bruce G. , Sangha Randeep S. , Ernst D. Scott , Pili Roberto , Kim Stella K. , Reyno Leonard , Wiseman Aya , Trave Fabio , Anand Banmeet , Morrison Karen , Doñate Fernando , Kollmannsberger Christian K. 
Published: May 2018

Abstract
Purpose: To determine the safety, pharmacokinetics, and recommended phase II dose of an antibody–drug conjugate (ADC) targeting ectonucleotide phosphodiesterases-pyrophosphatase 3 (ENPP3) conjugated to monomethyl auristatin F (MMAF) in subjects with advanced metastatic renal cell carcinoma (mRCC).
Patients and Methods: Two phase I studies were conducted sequentially with 2 ADCs considered equivalent, hybridoma-derived AGS-16M8F and Chinese hamster ovary–derived AGS-16C3F. AGS-16M8F was administered intravenously every 3 weeks at 5 dose levels ranging from 0.6 to 4.8 mg/kg until unacceptable toxicity or progression. The study was terminated before reaching the MTD. A second study with AGS-16C3F started with the AGS-16M8F bridging dose of 4.8 mg/kg given every 3 weeks.
Results: The AGS-16M8F study (n = 26) closed before reaching the MTD. The median duration of treatment was 12 weeks (1.7–83 weeks). One subject had durable partial response (PR; 83 weeks) and 1 subject had prolonged stable disease (48 weeks). In the AGS-16C3F study (n = 34), the protocol-defined MTD was 3.6 mg/kg, but this was not tolerated in multiple doses. Reversible keratopathy was dose limiting and required multiple dose deescalations. The 1.8 mg/kg dose was determined to be safe and was associated with clinically relevant signs of antitumor response. Three of 13 subjects at 1.8 mg/kg had durable PRs (range, 100–143 weeks). Eight subjects at 2.7 mg/kg and 1.8 mg/kg had disease control &gt;37 weeks (37.5–141 weeks).
Conclusions: AGS-16C3F was tolerated and had durable antitumor activity at 1.8 mg/kg every 3 weeks. Clin Cancer Res; 24(18); 4399–406. ©2018 AACR.
Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1–3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma withFGFR3Alterations
Authors: Pal Sumanta K. , Rosenberg Jonathan E. , Hoffman-Censits Jean H. , Berger Raanan , Quinn David I. , Galsky Matthew D. , Wolf Juergen , Dittrich Christian , Keam Bhumsuk , Delord Jean-Pierre , Schellens Jan H.M. , Gravis Gwenaelle , Medioni Jacques , Maroto Pablo , Sriuranpong Virote , Charoentum Chaiyut , Burris Howard A. , Grünwald Viktor , Petrylak Daniel , Vaishampayan Ulka , Gez Eliahu , De Giorgi Ugo , Lee Jae-Lyun , Voortman Jens , Gupta Sumati , Sharma Sunil , Mortazavi Amir , Vaughn David J. , Isaacs Randi , Parker Katie , Chen Xueying , Yu Kun , Porter Dale , Graus Porta Diana , Bajorin Dean F. 
Published: May 2018

AbstractBGJ398, a potent and selective pan-FGFR antagonist, was prospectively evaluated in patients with metastatic urothelial carcinoma bearing a diverse array of FGFR3 alterations. Patients (N = 67) who were unable to receive platinum chemotherapy were enrolled. The majority (70.1%) had received two or more prior antineoplastic therapies. BGJ398 was administered orally at 125 mg/day on a 3 weeks on, 1 week off schedule until unacceptable toxicity or progression. The primary endpoint was the response rate. Among 67 patients treated, an overall response rate of 25.4% was observed and an additional 38.8% of patients had disease stabilization, translating to a disease control rate of 64.2%. The most common treatment-emergent toxicities were hyperphosphatemia, elevated creatinine, fatigue, constipation, and decreased appetite. Further examination of BGJ398 in this disease setting is warranted.Significance: BJG398 is active in patients with alterations in FGFR3, resulting in both reductions in tumor volume and stabilization of disease. Our data highlight putative mechanisms of resistance to the agent, which may be useful in following disease status. Cancer Discov; 8(7); 812–21. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 781
“Sectual” Performance in Rule Texts
Authors: Miller Shem 
Published: May 2018

Abstract
In this article, I examine descriptions of community meetings in Rule Texts to outline the content, authority, and functions of membership’s oral performance in the sectarian movement associated with the Dead Sea Scrolls. In particular, I explore portrayals of oral performance during local chapter meetings (1QS 6:1b–7a), nightly study sessions (1QS 6:7b–8a), general membership meetings (1QS 6:8b–13a; CD 14:3b–12a), covenant renewal ceremonies (1QS 1:24–26; CD 20:27–30), admission procedures (1QS 5:7c–9a, 6:13b–23; CD 15:5b–10a), and a meeting of Israel in the last days (1QSa 1:1–6a). Overall, I argue that oral performance consistently played a vital role in members’ lives, whenever and wherever they lived.
Once Again on Word Order in the War Scroll (1QM)
Authors: Siegismund Kasper 
Published: May 2018

Abstract
This contribution offers a critical evaluation of John Screnock’s hypothesis that the basic word order in 1QM is subject-verb, with inversion triggered by fronting of non-subject elements or by the use of intransitive verbs. After a detailed examination of the evidence, the opposite conclusion is reached. Basic word order is verb-subject, with inversion to subject-verb order with pragmatically marked subjects (focus fronting). There seems to be no causal relationship between transitivity and word order. Furthermore, it is argued that Screnock’s interpretation of 1QM 1:1–3 (which flows from his transitivity-based analysis) is highly unlikely, as it leads to a division of sentences that would produce a structure practically unattested in the rest of the text. In addition, the findings are applied to the general discussion of word order in Hebrew, in particular as an argument against recent attempts at describing Biblical Hebrew as a language with basic subject-verb order.
The ‘Datasphere’, Data Flows beyond Control, and the Challenges for Law and Governance
Authors: Bergé Jean-Sylvestre , Grumbach Stéphane , Zeno-Zencovich Vincenzo 
Published: May 2018

The flows of people, goods and capital, which have considerably increased in recent history, are leading to crises (e.g., migrants, tax evasion, food safety) which reveal the failure to control them. Much less visible, and not yet included in economic measurements, data flows have increased exponentially in the last two decades, with the digitisation of social and economic activities. A new space – Datasphere – is emerging, mostly supported by digital platforms which provide essential services reaching half of the world’s population directly. Their control over data flows raises new challenges to governance, and increasingly conflicts with public administration.
In this paper, we consider the need and the difficulty of regulating this emerging space and the different approaches followed on both sides of the Atlantic. We distinguish between three situations. We first consider data at rest, which is from the point of view of the location where data are physically stored. We then consider data in motion, and the issues related to their combination. Finally, we investigate data in action, that is data as vectors of command of legal or illegal activities over territories, with impacts on economy and society as well as security, and raise governance challenges.
The notion of ‘Datasphere’ proposes a holistic comprehension of all the ‘information’ existing on earth, originating both in natural and socio-economic systems, which can be captured in digital form, flows through networks, and is stored, processed and transformed by machines. It differs from the ‘Cyberspace’, which is mostly concerned with the networks, the technical instruments (from software and protocols to cables and data centers) together with the social activities it allows, and to what extent they could/should be allowed.
The paper suggests one – out of the many possible – approach to this new world. Clearly it would be impossible to delve in depth into all its facets, which are as many as those of the physical world. Rather, it attempts to present how traditional legal notions could be usefully managed to put order in a highly complex environment, avoiding a piecemeal approach that looks only at details.
Don Carlos Infante of Spain
Authors: Schiller Friedrich 
Published: May 2018

Schiller’s Don Carlos, written ten years before his great Wallenstein trilogy, testifies to the young playwright’s growing power. First performed in 1787, it stands at the culmination of Schiller’s formative development as a dramatist and is the first play written in his characteristic iambic pentameter. Don Carlos plunges the audience into the dangerous political and personal struggles that rupture the court of the Spanish King Philip II in 1658. The autocratic king’s son Don Carlos is caught between his political ideals, fostered by his friendship with the charismatic Marquis Posa, and his doomed love for his stepmother Elisabeth of Valois. These twin passions set him against his father, the brooding and tormented Philip, and the terrible power of the Catholic Church, represented in the play by the indelible figure of the Grand Inquisitor.
Schiller described Don Carlos as "a family portrait in a princely house.” It interweaves political machinations with powerful personal relationships to create a complex and resonant tragedy. The conflict between absolutism and liberty appealed not only to audiences but also to other artists and gave rise to several operas, not least to Verdi’s great Don Carlos of 1867. The play, which the playwright never finished to his satisfaction, lives on nonetheless among his best-loved works and is translated here with flair and skill by Flora Kimmich. Like her translations of Schiller’s Wallenstein and his Fiesco’s Conspiracy at Genoa, this is a lively and accessible rendering of a classic text. As with all books in the Open Book Classics series, it is supported by an introduction and notes that will inform and enlighten both the student and the general reader.
Reliability and Climatological Impacts of Convective Wind Estimations
Authors: Edwards Roger , Allen John T. , Carbin Gregory W. 
Published: May 2018

AbstractConvective surface winds in the contiguous United States are classified as severe at 50 kt (58 mi h−1, or 26 m s−1), whether measured or estimated. In 2006, NCDC (now NCEI) Storm Data, from which analyzed data are directly derived, began explicit categorization of such reports as measured gusts (MGs) or estimated gusts (EGs). Because of the documented tendency of human observers to overestimate winds, the quality and reliability of EGs (especially in comparison with MGs) has been challenged, mostly for nonconvective winds and controlled-testing situations, but only speculatively for bulk convective data. For the 10-yr period of 2006–15, 150 423 filtered convective-wind gust magnitudes are compared and analyzed, including 15 183 MGs and 135 240 EGs, both nationally and by state. Nonmeteorological artifacts include marked geographic discontinuities and pronounced “spikes” of an order of magnitude in which EG values (in both miles per hour and knots) end in the digits 0 or 5. Sources such as NWS employees, storm chasers, and the general public overestimate EGs, whereas trained spotters are relatively accurate. Analysis of the ratio of EG to MG and their sources also reveals an apparent warning-verification-influence bias in the climatological distribution of wind gusts imparted by EG reliance in the Southeast. Results from prior wind-tunnel testing of human subjects are applied to 1) illustrate the difference between measured and perceived winds for the database and 2) show the impact on the severe-wind dataset if EGs were bias-corrected for the human overestimation factor.
Use of Ensemble Forecasts to Investigate Synoptic Influences on the Structural Evolution and Predictability of Hurricane Alex (2016) in the Midlatitudes
Authors: González-Alemán Juan Jesús , Evans Jenni L. , Kowaleski Alex M. 
Published: May 2018

Abstract
Hurricane Alex was an extremely rare hurricane event, the first North Atlantic hurricane to form in January since 1938. Alex developed from an extratropical low pressure system that formed over the western North Atlantic basin, and then underwent tropical transition after moving to the eastern basin. It subsequently underwent anomalous extratropical transition (ET) just north of the Azores Islands. We examine the factors affecting Alex’s structural evolution and the predictability of that evolution. Potential scenarios of structural development are identified from a 51-member forecast ensemble from the European Centre for Medium-Range Weather Forecasts Ensemble Prediction System (ECMWF-EPS), initialized at 0000 UTC 10 January 2016. The EPS forecasts are clustered using a regression mixture model based on the storm’s path through the cyclone phase space. Composite maps constructed from these clusters are used to investigate the role of synoptic-scale features on the evolving structure of Hurricane Alex as it interacted with the midlatitude flow. Results suggest that the crucial factor affecting this interplay was the behavior of a large extratropical cyclone and its associated cold front and likely warm conveyor belt upstream of Alex; the intensity of these structures determined whether Alex underwent a typical cold-core ET (as observed) or a warm-seclusion ET. The clustering and compositing methodology proposed not only provides a nuanced analysis of the ensemble forecast variability, helping forecasters to analyze the predictability of future complex tropical–midlatitude interactions, but also presents a method to investigate probable causes of different processes occurring in cyclones.
Evaluation of a Healthy Chinese Take-Out Sodium-Reduction Initiative in Philadelphia Low-Income Communities and Neighborhoods
Authors: Ma Grace X. , Shive Steven E. , Zhang Guo , Aquilante Jennifer , Tan Yin , Pharis Meagan , Bettigole Cheryl , Lawman Hannah , Wagner Amanda , Zhu Lin , Zeng Qiaoling , Wang Min Qi 
Published: May 2018

Objectives: Sodium reduction in restaurant foods is important because 77% of sodium in the United States is consumed by eating prepared and restaurant foods. We evaluated a sodium-reduction intervention, Healthy Chinese Take-Out Initiative, among Chinese take-out restaurants in low-income neighborhoods in Philadelphia, Pennsylvania. Our objectives were to (1) analyze changes in the sodium content of food samples and (2) collect data on changes in chefs’ and owners’ knowledge about the health risks of sodium overconsumption, perceptions of the need for sodium reduction, self-efficacy for lowering sodium use, and perceptions of training needs for sodium-reduction strategies. Methods: The initiative trained chefs from 206 Chinese take-out restaurants on strategies to reduce sodium in prepared dishes. We analyzed changes in the sodium content of the 3 most frequently ordered dishes—shrimp and broccoli, chicken lo mein, and General Tso’s chicken—from baseline (July-September 2012) to 36 months after baseline (July-September 2015) among 40 restaurants. We conducted a survey to examine the changes in chefs’ and owners’ knowledge, perceptions, and self-efficacy of sodium reduction. We used multilevel analysis and repeated-measures analysis of variance to examine effects of the intervention on various outcomes. Results: We found significant reductions in the sodium content of all 3 dishes 36 months after a low-sodium cooking training intervention (coefficients range, –1.06 to –1.69, P < .001 for all). Mean knowledge (range, 9.2-11.1), perceptions (range, 4.6-6.0), and self-efficacy (range, 4.2-5.9) ( P < .001 for all) of sodium reduction improved significantly from baseline (August 2012) to posttraining (also August 2012), but perceptions of the need for sodium reduction and self-efficacy for lowering sodium use returned to baseline levels 36 months later (August 2015). Conclusions: The intervention was a useful population health approach that led to engaging restaurants in sodium-reduction practices. Local public health agencies and professionals could partner with independent restaurants to introduce environmental changes that can affect population health on a broad scale, particularly for vulnerable populations.
Short- and long-term effects of pulmonary rehabilitation for idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Authors: Cheng Li , Tan Botao , Yin Ying , Wang Sanrong , Jia Lang , Warner Gerry , Jia Gongwei , Jiang Wei 
Published: May 2018

Objective:To investigate the short- and long-term effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis (IPF).Data sources:An electronic search of MEDLINE, Embase and Cochrane Central databases along with hand search of relevant papers were performed on 15 March 2018.Review methods:This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the literature for randomized controlled trials of pulmonary rehabilitation in IPF patients. The outcomes were exercise capacity and health-related quality of life. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan and STATA software.Results:We extracted data from four randomized controlled trials (142 participants). At short-term follow-up, pulmonary rehabilitation significantly enhanced 6-minute walk distance (6-MWD; weighted mean difference (WMD) = 38.38, 95% confidence interval (CI) = 4.64–72.12, I2 = 60.7%; P < 0.05), reduced St. George’s Respiratory Questionnaire (SGRQ)/IPF-specific SGRQ (SGRQ-I) total score (WMD = –8.40, 95% CI = –11.44 to −5.36, I2 = 0%; P < 0.00001). At long-term follow-up, pulmonary rehabilitation could not enhance 6-MWD (WMD = 17.02, 95% CI = –26.87 to 60.81, I2 = 36.3%; P = 0.43) or reduce SGRQ/SGRQ-I total score (WMD = –3.45, 95% CI = –8.55 to 1.64, I2 = 38.3%; P = 0.088).Conclusion:In patients with IPF, pulmonary rehabilitation showed short-term effects in enhancing exercise capacity and health-related quality of life, while it had no detectable effects at long-term follow-up.
Early cannulation grafts for haemodialysis: An updated systematic review
Authors: Shakarchi Julien Al , Inston Nicholas 
Published: May 2018

Purpose: Early cannulation grafts are specifically designed for dialysis, whereas standard expanded polytetrafluoroethylene grafts were not. There is developing collective experience and literature available to allow the assessment of outcomes of these early cannulation grafts. The aim of this review was to review the evidence for both short- and long-term outcomes of early cannulation grafts. Methods: Using standardized searches of electronic databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the primary outcomes for this study were primary and secondary patency rates for early cannulation grafts for dialysis at 12 months and beyond. Secondary outcomes were timing of first cannulation, rates of access thrombosis, steal syndrome, pseudo-aneurysm and infection. Results: A total of 19 studies were identified and included. These were divided into different graft types. Flixene™, Avflo™, Acuseal™ and Vectra™ grafts all showed that early cannulation within 72 h is possible. Twelve-month pooled primary and secondary patency rates were 43.3% (95% confidence interval: 31.6–55.4) and 73.4% (95% confidence interval: 63–82.7) for the Flixene graft, 58.2% (95% confidence interval: 48–68.1) and 79.2% (95% confidence interval: 68–88.7) for the Avflo graft, 43.6% (95% confidence interval: 30.7–56.9) and 70.5% (95% confidence interval: 49.7–87.8) for the Acuseal graft and 63.7% (95% confidence interval: 53.4–73.4) and 85.8% (95% confidence interval: 82.9–88.4) for the Vectra graft. Data for outcome beyond 12 months were limited to the more recent studies. Conclusion: This review confirms that early cannulation is not detrimental on the early outcome of early cannulation graft patencies. It has also shown that both Vectra and Avflo grafts have adequate long-term patencies. The data do not allow specific graft recommendations, as comparative trials would be required.
Experience of developing a cataract care pathway
Authors: Kadyan Anju , Green Jennie , Sandramouli Soupramanien 
Published: May 2018

Background An integrated care pathway (ICP) was developed and piloted for cataract surgery in the ophthalmic department of a district general hospital in the UK. Objectives To evaluate the pilot care pathway for feasibility and acceptability. Methods Compliance with documentation, variance analysis and staff experience with the ICP were analysed for the pilot. Results Good compliance and variance assessment with the pilot document was noted. User involvement was deficient in certain user groups, like doctors and patients. Evaluation of the pilot project also identified certain shortcomings in the system development method. Conclusions Implementation of the audit recommendations has simplified the patient journey. Working group consultation including all user groups aims to increase ownership and modify the care pathway document to a universally acceptable format. Incorporation of audit and electronic care pathways are recommended to improve resource management and provide early benefits for users.