bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering antitumour response and resistance with intratumour heterogeneity (DARWIN II).
Authors: Hiley Crispin T. , Ahmad Tanya , Jamal-Hanjani Mariam , Abbosh Christopher , Ngai Yenting , Hackshaw Alan , Patterson Paul , Baijal Shobhit , Nicolson Marianne , Lester Jason Francis , Krebs Matthew , Ottensmeier Christian H.H , Fennell Dean Anthony , Schmid Peter , Ezhil Muthuveni , Danson Sarah , Steele Nicola L. , Middleton Gary William , Dive Caroline , Swanton Charles ,   On Behalf of the TRACERx Consortium
Published: September 2018

TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised as a driver of cancer progression and survival outcome. However understanding how tumour clonal heterogeneity impacts upon therapeutic outcome is still an area of unmet clinical and scientific need. The TRACERx trial (NCT01888601), a prospective study of patients with radically resected primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through genetic analysis of multi-region and longitudinal tumour sampling. DARWIN II is an investigator initiated study for patients who are enrolled within the TRACERx trial, or who have multi-region sequencing of their primary disease, but subsequently relapse with metastatic disease. This study will examine the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy. Methods: This multicentre non-randomised phase II molecularly stratified umbrella study will examine how clonal dominance and ITH influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between ITH and cfDNA/CTCs will also be explored in DARWIN II. The study arms: Arm 1: Patients either -1) without an actionable mutation and PDL1 positive or 2) without an actionable mutation and PDL1 negative following first line cytotoxic chemotherapy - Atezolizumab. Arm 2: BRAFV600 - Vemurafenib. Arm 3: ALK/RET gene rearrangement - Alectinib. Arm 4: Her2 Amplification - Trastuzumab Emtansine. Primary Outcome Measures: Progression free survival (PFS), defined as the period between the date of registration to the date of subsequent progression or death will be assessed according to: Neo-antigen burden, mutational burden, ITH as assessed using an ITH ratio index and genomic instability as assessed using a weighted genome instability index (wGII). Trial Sponsor: University College London. Clinical trial information: NCT02314481.
A phase II study of oral azacitidine (CC-486) in combination with pembrolizumab (PEMBRO) in patients with metastatic melanoma (MM).
Authors: Keung Emily , Burton Elizabeth M. , Amaria Rodabe Navroze , Glitza Isabella Claudia , Patel Sapna Pradyuman , Diab Adi , Yee Cassian , Wong Michael K , Hwu Wen-Jen , Hwu Patrick , Woodman Scott Eric , Tetzlaff Michael T. , Milton Denai , Perez Kristen , Davies Michael A. , Rai Kunal , Wargo Jennifer Ann , Tawbi Hussein Abdul-Hassan 
Published: September 2018

TPS9594 Background: Immune checkpoint inhibitors have impressive response rates and improved survival for many pts with MM, offering durable responses in up to 35% of pts while others have short-lived or no response ( > 40%). A potentially targetable mechanism for immune escape is for cancers to subvert the cellular epigenetic machinery, affecting multiple aspects of the immune response from suppression of tumor antigen expression [such as Cancer Testis Antigens (CTA)] to antigen processing and presentation, thus allowing tumor proliferation to continue undetected. In preclinical models, decitabine (DAC), a DNA hypomethylating agent (HMA), has been able to revert heterogeneous CTA expression profiles, increasing cancer cell immunogenicity. HMAs also increased TH1-chemokine expression, T cell tumor infiltration, T cell-mediated tumor killing, and have been shown to be synergistic with checkpoint inhibitors in preclinical models. This suggests that epigenetic therapy with checkpoint inhibition is a rational combination to target MM. Clinical advantages of the HMA CC-486 over DAC include oral bioavailability and potential versatility in dosing and schedule. We hypothesize that CC-486 + PEMBRO will be tolerated at biologically relevant doses; enhance response to PEMBRO in pts with mm who are PD-1 naïve; and reverse resistance to immunotherapy in pts refractory/resistant to PD-1 directed therapy. Methods: This study will evaluate the safety and efficacy of CC-486 + PEMBRO defined by Objective Response Rate (ORR) by RECIST 1.1 in pts with MM. Pts who are PD-1 naïve (Arm A, n = 36) and pts who have progressed on prior PD-1 directed therapy (Arm B, n = 35) will be enrolled. Unlimited prior systemic therapies will be allowed. Pts will receive 300mg PO of CC-486 on days 1-14 and 200mg IV of PEMBRO every 3 weeks. Continuous monitoring for toxicity and futility will be performed and assumes an ORR of > 35% and > 15% for Arms A and B, respectively (95% power). Tumor biopsies at baseline and post treatment are required. Effects of CC-486 + PEMBRO on CTAs, MDSCs and Tregs, and correlation between mutation burden and response will be studied. This study is open for enrollment. Clinical trial information: NCT02816021.
SECOMBIT (sequential combo immuno and target therapy study): A three arms prospective, randomized phase II study to evaluate the best sequential approach with combo immunotherapy [ipilimumab (I) /nivolumab (N)] and combo target therapy [encorafenib (E)/binimetinib (B)] in patients with metastatic melanoma and BRAF mutation.
Authors: Ascierto Paolo Antonio , Dummer Reinhard , Melero Ignacio , Palmieri Giuseppe , Giannarelli Diana , Abrami Elena , Curvietto Marcello , Simeone Ester , Grimaldi Antonio Maria 
Published: September 2018

TPS9598 Background: Treatment of BRAF-mutated metastatic melanoma has dramatically changed with the introduction of targeted therapy (BRAF and MEK inhibitors) and immune-checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). Target therapy has been associated with high response rates, but short-term responses. Conversely, treatment with immune checkpoint inhibitors was found to present with lower response rates, but long-term responses. Synergism has been demonstrated when targeted therapy is combined with immunotherapy. The risk of a high rate of toxicity limits the simultaneous combination of all the four compounds (target agents and immunomodulating monoclonal antibodies). Sequencing of these different combinations seems to be more feasible; finding the right treatment sequence represents an important issue to be addressed. Methods: Approximately, 230 patients with untreated, histologically-confirmed advanced melanoma (measurable disease by RECIST v1.1) and carrying the BRAFV600 mutation will be randomized to Arm A [E+B until disease progression (PD), followed by I+N], or Arm B (I+N until PD, followed by E+B) or Arm C (E+B for 8 weeks, followed by I+N until PD, followed by E+B until PD). Patients will receive the combo treatments with the following schedules: target therapy, E 450mg p.o. od + B 45mg p.o. bid; immunotherapy, I 3mg/kg + N 1mg/kg Q3w x 4 cycles, followed by N 3mg/kg Q2w. The OS (time from the date of randomization until death from any cause) is primary efficacy endpoint of the study. Secondary endpoints include total PFS (time from randomization until the second progression), survival at 2 and 3 years, best overall response rate, duration of response. About 90 patients will take part in the ancillary study for the evaluation of biomarkers on the biological samples available (biopsies + blood samples). 30 Sites in Europe will concur to enroll the patients in the trial. This study is open and currently enrolling patients. Clinical trial information: NCT02631447.
Head-mounted sensors reveal visual attention of free-flying homing pigeons
Authors: Kano Fumihiro , Walker James , Sasaki Takao , Biro Dora 
Published: September 2018

ABSTRACTGaze behavior offers valuable insights into attention and cognition. However, technological limitations have prevented the examination of animals' gaze behavior in natural, information-rich contexts; for example, during navigation through complex environments. Therefore, we developed a lightweight custom-made logger equipped with an inertial measurement unit (IMU) and GPS to simultaneously track the head movements and flight trajectories of free-flying homing pigeons. Pigeons have a limited range of eye movement, and their eye moves in coordination with their head in a saccadic manner (similar to primate eye saccades). This allows head movement to act as a proxy for visual scanning behavior. Our IMU sensor recorded the 3D movement of the birds' heads in high resolution, allowing us to reliably detect distinct saccade signals. The birds moved their head far more than necessary for maneuvering flight, suggesting that they actively scanned the environment. This movement was predominantly horizontal (yaw) and sideways (roll), allowing them to scan the environment with their lateral visual field. They decreased their head movement when they flew solo over prominent landmarks (major roads and a railway line) and also when they flew in pairs (especially when flying side by side, with the partner maintained in their lateral visual field). Thus, a decrease in head movement indicates a change in birds' focus of attention. We conclude that pigeons use their head gaze in a task-related manner and that tracking flying birds' head movement is a promising method for examining their visual attention during natural tasks.
A Theoretical Study on Redox Potential and pKa of [2Fe-2S] Cluster Model from Iron-Sulfur Proteins
Authors: Kurniawan Isman , Kawaguchi Kazutomo , Shoji Mitsuo , Matsui Toru , Shigeta Yasuteru , Nagao Hidemi 
Published: September 2018

Abstract
Iron-sulfur proteins are essential in several biological processes, such as electron transfers in photosystems and respiratory chains. The range of redox potentials of these proteins are so wide that many substrates can interact with them. Thus, the redox potentials of the iron-sulfur proteins are crucial to facilitate the process. This study aims to investigate the redox potential of iron-sulfur proteins with [2Fe-2S] core by using two typical exchange-correlation functionals in density functional theory (DFT), i.e., B3LYP and M06, with and without the diffuse function. Since it involves transition metals, several types of spin approximation were also explored, such as high spin (HS), low spin (LS), approximated spin projection (AP), and J coupling parameter (JC) methods. We found that the diffuse function contributes to improving the accuracy. We also found that M06 functional produced more accurate results than B3LYP. The best result is obtained for AP UM06/6-31++G(d,p) with the absolute error of 0.01 V.
ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI MINAT PEMANFAATAN DAN PENGGUNAAN SISTEM INFORMASI (Studi pada Pemerintah Daerah Kabupaten Bantul)
Authors: Prasetiya Muhammad Erwin , Yuliantoro Rohmad 
Published: September 2018

The main purpose of this research is to examine the inflence of performance expactation of business and social factor, factor the suitability of assigments of interest utilizing information system and test the influence of conditions that facilitate user and system utilization onformation of interest in the use of information system has brought a very fundamental changes for the organization whether private or public organizations. Therefore, information system become very important in determining competitiveness and the ability of the company to improve business performance in the future. Population in this research in Goverment employees Bantul Regency. The technique to gather sample is judgmental technique (purposive). Data collected by using a questionnaire. 146 questionnaire returned from 200 sent and only 115 that can be processed. Data analysis was done using regression technique. The yhpothesis of this research was tested by using a two-equation of regression. The results of this research show thaat performance expectations, expectations of business, social factors, and the suitability of the tasks affect the interest of the utilization of information systems. The conditions that facilitate user do not affect the use of the system of information and interest of the utilization of information systems affect the use of system information.
Supporting failing students: How collaboration is key
Authors: Power Alison , Albaradura Olivia 
Published: September 2018

Nursing and Midwifery Council (NMC) standards state that the balance between clinical practice and theory in pre-registration midwifery programmes must be no less than 50% practice and no less than 40% theory, with students being supported by ‘midwife teachers’ and ‘midwife mentors’ ( NMC, 2009:18 ). Midwife teachers are expected to be involved in learning and assessment in both academic and practice learning environments by engaging in activities such as link tutoring; facilitating mentor development and updates; having a part-time clinical role or being involved with practice development, midwives' continuing professional development (CPD) or practice-based research activities. Clinical practice is supervised and graded by sign-off mentors, ‘gatekeepers to the profession’ who confirm that students are clinically competent, commensurate with their level of training, and are fit for entry to the midwives' part of the register at the end of their 3-year programme of study. This article will consider the importance of a collaborative approach between universities and clinical placement providers, particularly in relation to supporting failing students as, while ‘there has to be the recognition that some students need to fail’, sometimes students just require more focused support and planning to achieve the required skills, competencies and confidence in practice.
Trends in slipped capital femoral epiphysis: Is the rate declining?
Authors: Gutman I. M. , Gilbert S. R. 
Published: September 2018

Purpose Slipped capital femoral epiphysis (SCFE) is an adolescent hip condition with a high risk of complication. The purpose of this study was to evaluate trends in treatment using a prospectively collected paediatric nationally representative database. Methods A total of 9034 patients undergoing treatment for idiopathic SCFE were selected by querying the Healthcare Cost and Utilization Project's Kids’ Inpatient Database for the years 1997, 2000, 2003, 2006, 2009 and 2012. The selected patients were separated based on operative approach and these cohorts were analyzed based on temporal and categorical differences in operative approach, patient demographics and clinical characteristics. Univariate and multivariate analyses were used when appropriate and the Mantel-Haenszel test for trend was used in temporal analysis. Results Overall SCFE procedures have decreased 27.5% (p < 0.001). Closed procedures have decreased 28.5% (p < 0.001), while open procedures have decreased 44.8% (p < 0.001). Bilateral closed procedures have increased 7.2% (p < 0.001). The ratio of open to closed procedures decreased in patients aged nine to 12 years and increased in patients aged 13 to 16 years (p < 0.001). Conclusion Here we report age stratified trends in treatment for idiopathic SCFE using nationally representative data and show an overall decrease in admissions and procedures over time. Level of Evidence Level III, retrospective comparison study
Lack of Influence by CYP3A4 and CYP3A5 Genotypes on Pain Relief by Hydrocodone in Postoperative Cesarean Section Pain Management
Authors: Hosseinnejad Keivan , Yin Tyler , Gaskins Jeremy T , Stauble M Elaine , Wu Yanhong , Jannetto Paul , Langman Loralie L , Jortani Saeed A 
Published: September 2018

Abstract

Background
Genetic polymorphisms of cytochrome P450 are contributors to variability in individual response to drugs. Within the P450 family, CYP2D6 is responsible for metabolizing hydrocodone, a widely prescribed opioid for pain management. Alternatively, CYP3A4 and CYP3A5 can form norhydrocodone and dihydrocodeine. We have previously found that in a postcesarean section cohort, the rate of hydromorphone formation was dependent on the genotype of CYP2D6 and that plasma hydromorphone, not hydrocodone, was predictive of pain relief.

Method
Blood was obtained from a postcesarean cohort that were surveyed for pain response and common side effects. Plasma samples were genotyped for CYP3A4/5, and their hydrocodone concentrations were measured by LC-MS. R statistical software was used to check for differences in the outcomes due to CYP3A4/5 and CYP2D6, and a multivariate regression model was fit to determine factors associated with pain score.

Results
Two-way ANOVA between CYP3A4/A5 and CYP2D6 phenotypes revealed that the former variants did not have a statistical significance on the outcomes, and only CYP2D6 phenotypes had a significant effect on total dosage (P = 0.041). Furthermore, a 3-way ANOVA analysis showed that CYP2D6 (P = 0.036) had a predictive effect on plasma hydromorphone concentrations, and CYP3A4/A5 did not have any effect on the measured outcomes.

Conclusions
With respect to total dosages in a cesarean section population, these results confirm that CYP2D6 phenotypes are predictors for plasma hydromorphone concentration and pain relief, but CYP3A4/A5 phenotypes have no influence on pain relief or on side effects.
Extracting the Contingency Curve of Fuel Cost-Pollution the Issue of Environmental Economic Burden Distribution
Authors: KOSHTEH MH Karim 
Published: September 2018

In recent decades, SO2, CO2 and NOx emissions from fossil fuels have caused significant social costs. Considering the cost of environmental pollution combined with the cost of exploitation in the distribution of loads in many studies shows the important role of social spending in economic estimates. Minimizing the cost of exploitation along with the cost of emissions in order to meet the demand under the applicable constraints of the power systems known as the modeling of the problem of economic- environmental distribution is load EED (Environmental Economic Dispatch). In this research, the EED problem modeling is optimized by Lagrange’s analytical method based on weight coefficients for the six- generation system. The relationship between EER (Emission Reduction Rate) emission reduction index and fuel cost reduction coefficient is determined and, finally, the extraction of the fuel- pollutant- cost indifference curve is described. Sensitivity analysis has been carried out to achieve the final point of operation of the system, the fuel cost reduction coefficient and the cost- dependency curve of fuel- polluting units. The results are based on these principles:

The higher the weight loss factor is the greater the cost of fuel. The cost of operating the system is lower and the cost of emissions is higher. In this case, the problem of the economic distribution of burden or ED (Economic Dispatch) and the minimization of the cost of fuel is the object of the problem.
The lower the weight loss factor for fuel costs. The cost of operating the system is higher and the cost of pollution is reduced. In this case, minimizing the cost of emissions is the goal of the problem.
The combination of modeling results with indifference curves makes the final point of the system operator clear as the optimal answer to the problem. Utilizing the point of the final operation of the system as the answer to the problem, considering the importance of each goal and how cost and pollution changes are compared to each other.
Wireless video transmission into the MRI magnet room: implementation and evaluation at 1.5T, 3T and 7T
Authors: Hensen Bennet , Kägebein Urte , Gutberlet Marcel , Ringe Kristina I. , Vo-Chieu Van Dai , Stucht Daniel , Speck Oliver , Vick Ralf , Wacker Frank , Pannicke Enrico 
Published: September 2018

Abstract

Purpose
To analyze the interference between a wireless high definition multimedia interface (WHDMI) and magnetic resonance imaging (MRI) image quality at 1.5T, 3T and 7T.

Materials and methods
A wireless video transmission system (WVTS) consisting of a WHDMI and a projector was used to transmit and display a video stream into the magnet room. MR image quality was analyzed at 1.5T, 3T and 7T. Signal-to-noise-ratio

$(\overline {{\rm{SNR}}} )$
and radio frequency (RF)-noise spectrum were measured at three transmitter positions (A: inside the cabin, B: in front of the waveguide and C: in the control room). WVTS system functionality tests included measurements of reliability, delay and image quality.

Results
With the WVTS mean

$\overline {{\rm{SNR}}} $
values significantly decreased in comparison to the reference for all positions and fieldstrenghts, while the spectra’s baseline is elevated at 1.5T and 3T. Peaks related to continuous wave interferences are apparent at all field strenghts. For WHDMI alone mean

$\overline {{\rm{SNR}}} $
values were stable without significant differences to the reference. No elevation of the spectra’s baseline could be observed. Functionality measurements confirmed high connection reliability with stable image quality and no delays for all field strengths.

Conclusion
We conclude that wireless transmission of video streams into the MRI magnet room is feasible at all field strengths without hampering image quality.
Tort Law and Mass Transportation Accidents: A French-German View on Legal Challenges in Times of Market Deregulation
Authors: Knetsch Jonas 
Published: September 2018

Abstract
The liberalisation of the coach, air and rail transport market sheds new light on a relatively unexplored field of comparative tort law: the rules governing the liability of transportation companies for accidents involving third parties. Through an assessment of recent developments under French and German Law, this article reflects on the emerging trends of those tort rules, induced or highlighted by the market opening process. The existing strict liability regimes for railway and coach carriers, already subject to a significant tightening process, raise new questions as to the exact circle of persons liable for injuries, since the market liberalisation goes hand in hand with the unbundling of infrastructure and operations.
Das Wort zwischen Mystik und Humanismus – Luthers Gewissheit und sein Machtanspruch
Authors: Albrecht Johannes-Friedrich 
Published: September 2018

Zusammenfassung
Nach Luther soll das Evangelium nicht nur in der persönlichen Meditation des Wortes, sondern auch in der öffentlichen Verkündigung, erfahrbar werden. Dies verlangt von der Verkündigung, kritisch zu rechtlichen und sozialen Verhältnissen Stellung zu nehmen. In Spannung zu diesem Anliegen tritt Luthers Instrumentalisierung des Sprachhumanismus für sein Interesse an der objektivierenden Absicherung seiner Lehre durch die äußere Klarheit der Schrift. Der darin gründende Machtanspruch lässt einen antidialogischen und aggressiven Kommunikationsstil und eine feindselige Haltung insbesondere gegen das Judentum und seine eigenständige Schriftauslegung herrschend werden. Der Humanismus verliert damit seinen wesentlichen Gehalt. Doch eine Deutung der Schrift und der Wirklichkeit im Sinne der Christus-Mystik gewinnt erst durch einen offenen Prozess der Interpretation, durch Kontextualisierung, Selbstkritik und durch Dialog an Plausibilität. Die von Luther in der Christologie geforderten Perspektivenwechsel können nur so gelingen und ihre befreiende und Solidarität stiftende Kraft entfalten. Eine Abwertung des Judentums als Bundesvolk ist damit prinzipiell unvereinbar.