bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of avelumab in combination with cetuximab in pre-treated RAS wild-type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Authors: Troiani Teresa , Martinelli Erika , Ciardiello Davide , Zanaletti Nicoletta , Cardone Claudia , Borrelli Carola , Avallone Antonio , Falcone Alfredo , Maiello Evaristo , Bordonaro Roberto , Santini Daniele , Garufi Carlo , De Braud Filippo G. , Pinto Carmine , Gridelli Cesare , Ciardiello Fortunato 
Published: January 2019

TPS731 Background: The immune system plays a crucial role in modulating response to monoclonal antibodies therapy in cancer. Novel immunecheckpoint inhibitors have demonstrated potent efficacy alone and in combinations with cytotoxic agents in several cancers. In this regard, avelumab in combination with cetuximab might be a relevant rechallenge strategy in RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients treated in first-line with chemotherapy (CT) in combination with anti-EGFR drugs and who achieved a complete or partial response. Methods: CAVE Colon is a single arm, multi-center phase II study designed to evaluate the efficacy of avelumab and cetuximab in pre-treated RAS WT mCRC patients. Eligible patients: pathologically confirmed RAS WT mCRC treated with a first-line CT in combination with an anti-EGFR agent with a major response achieved (complete or partial), who have progressed to a second line therapy, and received no prior immunotherapy. Primary endpoint is overall survival, secondary endpoint are overall response rate according to RECIST 1.1, progression free survival and safety profile. The current study seeks to demonstrate a median OS of 11 months (alternative hypothesis) by the experimental combination for comparison with historical median OS 8.0 (null hypothesis) with standard third line treatments, which correspond to an improvement of OS at six months from 40% to 57%. It was estimated that it would be needed to enroll 66 patients to achieve a 80% power with a one-sided 5% level test. The accrual period will be 18 months and the total duration of the study will be 36 months. Considering a potential drop-out of approximately 15% of patients, a total of 75 patients will be recruited. Seven patients have been enrolled and started treatment to date (September 15, 2018) with avelumab 10 mg/kg q14 as a one-hour i.v. infusion and cetuximab at 400 mg/m2 over two-hour and subsequently 250 mg/m2 q 14 as one-hour i.v. infusion until disease progression or unacceptable toxicity. EudraCT number: 2017-004392-32. This study is partially supported by Merck KgA, Darmstadt, Germany. Results: N/A. Conclusions: N/A. Clinical trial information: EudraCT number: 2017-004392-32.
High Preponderance of BRAF V600E Mutation in Papillary Thyroid Carcinoma Among Filipinos: A Clinicopathologic Study
Authors: Espiritu Gerard Anthony M. , Malana Joemari T. , Dumasis Arlie Jean Grace V. , Ang Daphne C. 
Published: January 2019

Purpose BRAF mutation in papillary thyroid carcinoma (PTC) is associated with an aggressive phenotype, with varying incidence. We evaluated the prevalence of BRAF mutations in PTC among Filipino patients and their correlation with clinicopathologic characteristics. Patients and Methods Clinicopathologic data were retrieved from 64 sequential patients who underwent thyroidectomy from June 2016 to December 2016. BRAF mutation testing was performed using Sanger sequencing. Results Eighteen (28%) of 64 patients were diagnosed with PTC; 12 (70.59%) of 17 harbored a BRAF V600E mutation (no amplification in one patient). Demographics of patients with PTC were as follows: 13 women and five men, with median age of 46 years (range, 25 to 74 years). Fourteen patients had conventional subtype PTC; two, follicular variant; one, oncocytic variant; and one, tall-cell features. Tumor size ranged from 0.8 to 7.0 cm (median, 2.4 cm); extrathyroidal extension was present in seven (38.9%) of 18 patients, multifocality in six (33.33%) of eight, and lymph node involvement in eight (44.4%) of 18. Significant association between presence of a BRAF mutation and presence of extrathyroidal extension or lymph node involvement was not determined due to the limited sample size. Conclusion The high preponderance of BRAF mutation (70.59%) suggests some correlation with the previously reported lower 5-year survival among Filipinos. This warrants further investigation in a larger-cohort prospective study.
Cervical Cancer Treatment Delays and Associated Factors in a Cohort of Women From a Developing Country
Authors: Ferreira da Silva Ileia , Ferreira da Silva Ilce , Koifman Rosalina Jorge 
Published: January 2019

PURPOSETo estimate treatment delays and associated factors among women diagnosed with cervical cancer who were treated at the main cancer center in Rio de Janeiro, Brazil.MATERIALS AND METHODSA retrospective cohort study was performed comprising 865 women newly diagnosed with cervical cancer between 2012 and 2014. Times from diagnosis to treatment initiation (less than or equal to 60 days) and from diagnosis to treatment ending (less than or equal to 120 days) were analyzed according to the Brazilian law for the treatment of patients with cancer. Associations between treatment delays and sociodemographic, economic, lifestyle, clinical, and treatment variables were estimated using logistic regression models, with 95% CIs.RESULTSThe average age was 48 (± 13.7) years, and the median age was 47 years; 36.2% of patients had stage IIIB to IVA disease. The median time from diagnosis to treatment initiation was 114 days, which was statistically higher among women with stage IIB to IVA (105.5 days) compared with those with earlier stages (119 days). The delay in treatment initiation occurred in 92.8% of participants; the median time from diagnosis to treatment ending was 274 days, with a delay (more than 120 days) for 92.6% of patients. The median time interval from diagnosis to the first visit to the cancer center was 28 days, with a delay of more than 30 days for 46.6% of patients. Age (odds ratio [OR], 1.05; 95% CI,1.02 to 1.08), stage IIIB to IVA (OR, 0.38; 95% CI, 0.16 to 0.90), time to first visit to the cancer center (OR, 11.52; 95% CI, 4.32 to 30.66), chemoradiation treatment (OR, 4.56; 95% CI, 1.81 to 11.47), and adequate treatment (OR, 2.57; 95% CI, 1.26 to -5.40) were independently associated with delay of treatment initiation.CONCLUSIONSignificant delays in treatment initiation and ending were observed in this studied population. The treatment initiation delay was positively associated with age, time interval more than 30 days from diagnosis to first specialist assessment at the cancer center, treatment with chemoradiation, and adequate treatment.
Rab23/Kif17 regulate meiotic progression in oocytes by modulating tubulin acetylation and actin dynamics
Authors: Wang Hong-Hui , Zhang Yu , Tang Feng , Pan Meng-Hao , Wan Xiang , Li Xiao-Han , Sun Shao-Chen 
Published: January 2019

ABSTRACT
Cytoskeletal dynamics are involved in multiple cellular processes during oocyte meiosis, including spindle organization, actin-based spindle migration and polar body extrusion. Here, we report that the vesicle trafficking protein Rab23, a GTPase, drives the motor protein Kif17, and that this is important for spindle organization and actin dynamics during mouse oocyte meiosis. GTP-bound Rab23 accumulated at the spindle and promoted migration of Kif17 to the spindle poles. Depletion of Rab23 or Kif17 caused polar body extrusion failure. Further analysis showed that depletion of Rab23/Kif17 perturbed spindle formation and chromosome alignment, possibly by affecting tubulin acetylation. Kif17 regulated tubulin acetylation by associating with αTAT and Sirt2, and depletion of Kif17 altered expression of these proteins. Moreover, depletion of Kif17 decreased the level of cytoplasmic actin, which abrogated spindle migration to the cortex. The tail domain of Kif17 associated with constituents of the RhoA-ROCK-LIMK-cofilin pathway to modulate assembly of actin filaments. Taken together, our results demonstrate that the Rab23-Kif17-cargo complex regulates tubulin acetylation for spindle organization and drives actin-mediated spindle migration during meiosis.
An in vitro model for studying CNS white matter: functional properties and experimental approaches
Authors: Bijland Silvia , Thomson Gemma , Euston Matthew , Michail Kyriakos , Thümmler Katja , Mücklisch Steve , Crawford Colin L. , Barnett Susan C. , McLaughlin Mark , Anderson T. James , Linington Christopher , Brown Euan R. , Kalkman Eric R. , Edgar Julia M. 
Published: January 2019

The normal development and maintenance of CNS white matter, and its responses to disease and injury, are defined by synergies between axons, oligodendrocytes, astrocytes and microglia, and further influenced by peripheral components such as the gut microbiome and the endocrine and immune systems. Consequently, mechanistic insights, therapeutic approaches and safety tests rely ultimately on in vivo models and clinical trials. However, in vitro models that replicate the cellular complexity of the CNS can inform these approaches, reducing costs and minimising the use of human material or experimental animals; in line with the principles of the 3Rs. Using electrophysiology, pharmacology, time-lapse imaging, and immunological assays, we demonstrate that murine spinal cord-derived myelinating cell cultures recapitulate spinal-like electrical activity and innate CNS immune functions, including responses to disease-relevant myelin debris and pathogen associated molecular patterns (PAMPs). Further, we show they are (i) amenable to siRNA making them suitable for testing gene-silencing strategies; (ii) can be established on microelectrode arrays (MEAs) for electrophysiological studies; and (iii) are compatible with multi-well microplate formats for semi-high throughput screens, maximising information output whilst further reducing animal use. We provide protocols for each of these. Together, these advances increase the utility of this in vitro tool for studying normal and pathological development and function of white matter, and for screening therapeutic molecules or gene targets for diseases such as multiple sclerosis, motor neuron disease or spinal cord injury, whilst avoiding in vivo approaches on experimental animals.
Uso problemático de internet en adolescentes españoles y su relación con autoestima e impulsividad
Authors: Moral Jiménez María de la Villa , Fernández Domínguez Sara 
Published: January 2019

Dado el gran auge del uso de las nuevas tecnologías de la información y la comunicación (TIC) por parte del colectivo juvenil resulta de interés el análisis de los patrones disfuncionales y de su potencialidad adictiva. El objetivo de este trabajo consiste en explorar las relaciones entre el uso problemático de internet y factores de riesgo como la impulsividad, así como analizar las diferencias en conflictos intra e interpersonales asociados en función del género y la edad. Han participado 240 adolescentes y jóvenes (124 mujeres y 116 hombres) con edades comprendidas entre los 15 y 22 años (X= 18.075; DT= 2.36), estudiantes del Principado de Asturias (España). En relación con la posible existencia de usos problemáticos de internet resulta atribuible al 11.25% de los adolescentes frente a un 88.75% que muestran un uso controlado. Respecto a las diferencias en función del género y de la edad no han resultado significativas. Se ha hallado que la baja autoestima y la impulsividad cognitiva y no planeada predicen con mayor probabilidad el uso desadaptativo de internet. Presentar mayor propensión a tomar decisiones rápidas, así como mostrar más interés en las tomas de decisiones presentes que futuras, aumentan las probabilidades de puntuar más alto en conflictos interpersonales asociados al uso problemático de internet. Se discuten las implicaciones de tales hallazgos.Palabras clave: uso problemático, Internet, autoestima, impulsividad, adolescentes.
Mudanças na psicoterapia psicodinâmica de crianças na visão de pais e mães
Authors: Ramires Vera Regina Rohnelt , Carvalho Cibele , Gastaud Marina Bento , Oliveira Luiz Ronaldo Freitas de , Godinho Lucia Belina Rech 
Published: January 2019

No campo da pesquisa em psicoterapia psicodinâmica das crianças, uma questão aberta é como avaliar sistematicamente as mudanças e quais se consideram fundamentais. Não se têm levado a cabo análises qualitativas acerca da visão de país e mães. O objetivo deste estudo foi investigar a percepção de pais e mãessobre as possíveis mudanças em suas crianças durante suas psicoterapias. O estudo teve enfoque qualitativo, descritivo, longitudinal. Os participantes foram país e mães de quatro crianças, assistidos na clínica privada por três psicoterapeutas treinados em psicoterapia clínica.Eles responderam regularmente ao questionário de pergunta aberta que se centrou nas mudanças percebidasno curso do processo terapêutico. Os resultados mostraram que os pais têm identificado mudanças no curso da psicoterapia de seus filhos, que eles não eram lineais e não se limitaram à melhoria sintomática. Também se identificaram mudanças no funcionamento mental das crianças e sua adaptação à realidade, e nas relações interpessoais.Se discutiu a importância da participação dos pais na psicoterapia das crianças e o seguimento de sua visão acerca do processo terapêutico. Eles podem proporcionar feedbacks importantes que contribuem para o progresso do tratamento.Palabras-chave: psicoterapia psicanalítica, mudanças, crianças.
The Effect of Solution-Focused Brief Counseling on Reducing Test Anxiety
Authors: Altundağ Yunus , Bulut Sefa 
Published: January 2019

Test anxiety is a very common phenomena observed in K-12 level of education all over the world. This can take a more complex and stressful form in countires uses national exam in university entrance. Turkey is one of those countries. Since higher education is free for all of the citizen, students have found themselves confronting a very competitive testing-culture. Therefore, the purpose of this study was to test the effectiveness of solution-focused brief counseling approch on test anxiety of senior year high school students. An experimental study was conducted in an Anatolian High School in Bolu, Turkey in the academic year of 2015-2016. Sixteen students were participated in the study, eight of them were in the experimental group, other eight were in the control group. The ages of the students varied between 16 and 18 years; the average age of the experimental group was 17, while it was 16.87 in the control group. Six of the participants were male whereas ten were female. Because the data set was not normally distributed and number of participatns was less than 30, nonparametic tests were prefered for data analysis. Mann Whitney-U and Wilcoxon Signed Rank tests, which are nonparametric techniques, were utilized in data processing. The resuls revaled that the four-session individual psychological counseling based on solution-focused brief approach was effective in mitigating students' test anxiety. These findings were found to be consistent with the related literature.Keywords: Solution-Focused Brief approach, psychological counseling, test anxiety, adolescent, high school student, university entrance exam.
Estimates of Within-Subject Biological Variation Derived from Pathology Databases: An Approach to Allow Assessment of the Effects of Age, Sex, Time between Sample Collections, and Analyte Concentration on Reference Change Values
Authors: Jones Graham Ross Dallas 
Published: January 2019

AbstractBACKGROUNDWithin-subject biological variation data (CVI) are used to establish quality requirements for assays and allow calculation of the reference change value (RCV) for quantitative clinical laboratory tests. The CVI is generally determined using a large number of samples from a small number of individuals under controlled conditions. The approach presented here is to use a small number of samples (n = 2) that have been collected for routine clinical purposes from a large number of individuals.METHODSPairs of sequential results from adult patients were extracted from a routine pathology database for 29 common chemical and hematological tests. Using a statistical process to identify a central gaussian distribution in the ratios of the result pairs, the total result variation for individual results was determined for 26 tests. The CVI was then calculated by removing the effect of analytical variation.RESULTSThis approach produced estimates of CVI that, for most of the analytes in this study, show good agreement with published values. The data demonstrated minimal effect of sex, age, or time between samples. Analyte concentration was shown to affect the distributions with first results more distant from the population mean more likely to be followed by a result closer to the mean.DISCUSSIONThe process described here has allowed rapid and simple production of CVI data. The technique requires no patient intervention and replicates the clinical environment, although it may not be universally applicable. Additionally, the effect of regression to the mean described here may allow better interpretation of sequential patient results.
Pengaruh Aplikasi Streptomyces spp. Terhadap Penyakit Kuning, Pertumbuhan, dan Produksi Tanaman Cabai Besar
Authors: Putri Riska Awalia 
Published: January 2019

Penyakit keriting kuning cabai yang disebabkan oleh Begomovirus merupakan salah satu kendala produksi cabai di Indonesia. Salah satu alternatif pengendalian penyakit ini menggunakan Plant Growth Promoting Rhizobacter (PGPR) yang diharapkan dapat mengurangi penggunaan pestisida yang berdampak buruk bagi lingkungan dan kesehatan. Penelitian ini bertujuan untuk mengetahui efektifitas Streptomyces spp. dalam menekan penyakit keriting kuning, pertumbuhan tanaman dan hasil panen cabai besar. Penelitian dilakukan di lahan petani di Desa Harjobinangun, daerah Pakem, Kabupaten Sleman, Yogyakarta. Menggunakan varietas cabai Twist dan Isolat Streptomyces spp. koleksi Laboratorium Bakteriologi Tumbuhan dengan konsentrasi 108 CFU/ml. Hasil penelitian menunjukkan bahwa Streptomyces spp. mampu menurunkan insidensi dan intensitas penyakit pada fase vegetatif 54,17% dan 59,06%. Sedangkan pada fase generatif 50% dan 65,92%. Streptomyces spp. dapat meningkatkan tinggi dan diameter tanaman pada fase vegetatif 4,61% dan 6,05%. dan pada fase generatif 27,28% dan 1,11%. Streptomyces spp. dapat meningkatkan panjang akar, volume akar dan jumlah cabang produktif 4,40%, 20,70%, dan 24,81%. Streptomyces spp. dapat meningkatkan jumlah dan bobot total panen 15,5% dan 16,72%. Streptomyces spp. dapat meningkatkan kualitas buah ditunjukan dengan peningkatan panjang, diameter, dan bobot buah layak jual 6.26%, 12,80%, dan 11,39%.
Why Mathematical Probability Failed to Emerge from Ancient Gambling
Authors: Kidd Stephen 
Published: January 2019

AbstractThe emergence of mathematical probability has something to do with dice games: all the early discussions (Cardano, Galileo, Pascal) suggest as much. Although this has long been recognized, the problem is that gambling at dice has been a popular pastime since antiquity. Why, then, did gamblers wait until the sixteenth centuryceto calculate the math of dicing? Many theories have been offerred, but there may be a simple solution: early-modern gamblers played different sorts of dice games than in antiquity. While ancients diced at communal risk, early-moderns diced at individualized risk. These individual wager-games, for example, the game “hazard”, incentivized solving questions like “how likely is it to roll a triple-six?”. Before the early modern period there was no gambling game to which working out mathematical probability would have brought an advantage.
Equity Incentives and Crash Risk in China’s A-Share Market
Authors: Xu Jiahua 
Published: January 2019

Abstract
This paper examines the relationship between equity incentives and stock price crash risk in China’s A-Share Market, and finds a significantly positive relationship between equity incentives and crash risk. This result holds true when only executives’ incentives are involved, while the significance fades once non-managerial personnel’s incentives are considered, indicating a tendency for managers to manipulate the stock price when their interests are tied to the market value of the stock. This manipulation, however, can cause the stock price to suffer in subsequent years.
“The goal is to enable students to communicate”: Communicative competence and target varieties in TEFL practices in Sweden and Germany
Authors: Forsberg Julia , Mohr Susanne , Jansen Sandra 
Published: January 2019

AbstractThis paper compares teaching practices of English as a foreign language in Sweden and Germany based on a questionnaire targeted at investigating teachers’ experiences and views on language use, giving a snapshot of teaching practices in classrooms in the two countries. In this regard, the focus is on the following questions: Which target varieties are used in TEFL, and to what extent? What is the status of different target varieties among teachers of English in the two countries? The results show that the use of target varieties is still in play in the TEFL classroom, despite the recent move towards communicative competence as the goal. The main target varieties used are AmE, BrE, a mixture of the two, and some neutral variety; with a slight preference among German teachers for BrE and among Swedish for the neutral variety alongside AmE or BrE. Further, teachers are in conflict between two ideals: learned (where they teach an English belonging to the native speakers) and didactic (where the goal is communicative fluency). In application, this conflict should be addressed by teacher training programmes in order to make (future) teachers aware of it and provide possible ways to cope with it.
Evaluation of (power) side-channels in cryptographic implementations
Authors: Bache Florian , Plump Christina , Wloka Jonas , Güneysu Tim , Drechsler Rolf 
Published: January 2019

Abstract
Side-channel attacks enable powerful adversarial strategies against cryptographic devices and encounter an ever-growing attack surface in today’s world of digitalization and the internet of things. While the employment of provably secure side-channel countermeasures like masking have become increasingly popular in recent years, great care must be taken when implementing these in actual devices. The reasons for this are two-fold: The models on which these countermeasures rely do not fully capture the physical reality and compliance with the requirements of the countermeasures is non-trivial in complex implementations. Therefore, it is imperative to validate the SCA-security of concrete instantiations of cryptographic devices using measurements on the actual device. In this article we propose a side-channel evaluation framework that combines an efficient data acquisition process with state-of-the-art confidence interval based leakage assessment. Our approach allows a sound assessment of the potential susceptibility of cryptographic implementations to side-channel attacks and is robust against noise in the evaluation system. We illustrate the steps in the evaluation process by applying them to a protected implementation of AES.
Bioceramics: from bone substitutes to nanoparticles for drug delivery
Authors: Vallet-Regí María 
Published: January 2019

AbstractSince the second half of the 20thcentury, bioceramics are used for bone repair and regeneration. Inspired by bones and teeth, and aimed at mimicking their structure and composition, several artificial bioceramics were developed for biomedical applications. And nowadays, in the 21stcentury, with the increasing prominence of nanoscience and nanotechnology, certain bioceramics are being used to build smart drug delivery systems, among other applications. This minireview will mainly describe both tendencies through the research work carried out by the research team of María Vallet-Regí.