bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of afatinib in patients with advanced/metastatic urothelial carcinoma (UC) with genetic alterations in ERBB receptors 1-3 who failed on platinum-based chemotherapy (CT).
Authors: Font Pous Albert , Puente Javier , Castellano Daniel E. , Real Francisco X. , Climent Miguel A. , Gonzalez del Alba Aranzazu Aranzazu , Oudard Stephane , Vazquez Mazon Federico Jose , Morales Barrera Rafael , Virizuela Juan Virizuela , Sala Nuria , Pérez-Valderrama Begoña , Garcia del Muro Xavier , Fernandez Pedro L. , Jares Pedro , Aldecoa Iban , Gibson Neil , Serra Josep , Rodrigo Imedio Esteban , Mellado Begona 
Published: February 2018

TPS540 Background: First-line treatment of patients (pts) with advanced/metastatic UC consists of platinum-based CT, with no well-established subsequent therapy for platinum-refractory disease. Although checkpoint inhibitors have shown promising results recently, targeted agents have generally not demonstrated significant clinical activity in this setting. Around 20% of UC harbor ERBB family genetic alterations, as such it may be a suitable therapeutic target (Knowles, Nat Rev Cancer 2015;15:25–41). The irreversible ERBB family blocker, afatinib, has shown activity in a Phase II trial in a subset of pts with UC who had ERBB2/ERBB3 aberrations (Choudhury, J Clin Oncol 2016;34:2165–71). This Phase II trial will evaluate afatinib in pts with UC molecularly selected for ERBB receptor alterations. Methods: This single-arm trial will assess the efficacy and safety of afatinib in pts with UC harboring ERBB2/ERBB3 mutations or ERBB2 amplification (Cohort A), or EGFR (ERBB1) amplification (Cohort B). Eligible pts are ≥18 years of age with ECOG PS 0–1, histologically confirmed advanced/metastatic UC of the bladder, upper tract or urethra, not amenable to surgery and progressing during or after platinum-based CT, with available archival tissue samples for pre-screening biomarker analysis. Pts will receive oral afatinib 40 mg/day until disease progression or discontinuation. Cohort A is enrolling in two stages, with Stage 2 enrollment based on anti-tumor activity observed. The primary endpoint is progression-free survival (PFS) rate at 6 months; secondary endpoints include objective response rate, PFS, overall survival, disease control rate, duration of response and tumor shrinkage. Trial objectives will be analyzed separately for the two cohorts. Safety and biomarker assessments will also be performed. The trial commenced in June 2016; as of October 4, 2017, 201 samples have been analyzed, with 24.3% and 8% of pts with genetic alterations potentially eligible for inclusion in Cohort A and B, respectively. To date, 12 pts have received study treatment in Cohort A and 6 in Cohort B; recruitment is ongoing. Clinical trial information: NCT02780687.
Phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC).
Authors: Agarwal Neeraj , Vaishampayan Ulka N. , McGregor Bradley Alexander , Green Marjorie C. , Mohamed Nehal , Chang Pei-Yun , Powles Thomas , Pal Sumanta K. ,   For the XL184-021 Study Group
Published: February 2018

TPS541 Background: Cabozantinib (CABO) is an oral receptor tyrosine kinase inhibitor of MET, VEGFR, and TAM family receptors (TYRO3, AXL, and MER). It is approved for patients (pts) with RCC after prior therapy with antiangiogenic therapy, and has demonstrated clinical activity in UC. In clinical studies, CABO exposure increased circulating CD8+ T cells and reduced immune-suppressive monocytes and Tregs. In preclinical tumor models, CABO increased MHC class 1 expression on tumor cells and reduced myeloid-derived suppressor cells. CABO may facilitate an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors. Atezolizumab (ATEZO), an anti-PD-L1 mAb, is approved for: locally advanced/metastatic UC in pts who are cisplatin-ineligible or have disease progression during/following platinum-containing chemo; pts with metastatic NSCLC and disease progression during/following platinum-containing chemo. We present the study design of an ongoing phase 1b study combining CABO with ATEZO in pts with locally advanced/metastatic UC or RCC. Methods: This multicenter, phase 1b, open-label study aims to assess safety, tolerability, preliminary efficacy, and pharmacokinetics of CABO in combination with ATEZO (NCT03170960). The study will enroll pts with advanced UC (bladder, renal pelvis, ureter, urethra) or RCC. It consists of two stages: dose escalation and expansion. In the dose-escalation stage (3+3 design), a recommended CABO dose for the combination will be established. In the expansion stage, four tumor-specific cohorts will be enrolled: 1) pts with UC who have progressed on/after platinum-containing chemo; 2) chemo-naïve pts with UC who are cisplatin ineligible; 3) chemo-naïve pts with UC who are cisplatin eligible; and 4) untreated pts with RCC with clear cell histology; the primary objective is to determine the objective response rate in each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers, and changes in immune cell profiles with clinical outcome. The study has been initiated and enrollment target is 120 pts across the 4 expansion cohorts. Clinical trial information: NCT03170960.
A phase 2 trial of lenvatinib 18 mg versus 14 mg once daily (QD) in combination with everolimus (5 mg QD) in renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment.
Authors: Glen Hilary , Puente Javier , Heng Daniel Yick Chin , Rha Sun Young , Li Di , Stepan Daniel E. , Dutcus Corina E. , Pal Sumanta K. 
Published: February 2018

TPS707 Background: Based on findings from a randomized phase 2 study (Study 205), lenvatinib (LEN) + everolimus (EVE) was approved in the United States and European Union for patients (pts) with advanced RCC following 1 prior anti-angiogenic therapy. In that study, LEN 18 mg QD + EVE 5 mg QD significantly prolonged progression-free survival (PFS) compared with either monotherapy. In the LEN+EVE cohort, grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 71% of pts. We report the design of an ongoing, multicenter, randomized, double-blind, phase 2 study (Study 218) to evaluate if a lower LEN starting dosage regimen provides similar efficacy with a better safety profile than LEN 18 mg + EVE 5 mg (NCT03173560). Methods: Eligible pts are aged ≥ 18 years with advanced clear cell RCC, 1 prior anti-VEGF therapy, ≥ 1 measurable target lesion per RECIST 1.1, a KPS score of ≥ 70, and prior nivolumab is allowed. Pts will receive LEN 18 mg or 14 mg QD + EVE 5 mg QD in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The LEN 14-mg dose will be escalated to 18 mg if no intolerable grade 2, or any grade ≥ 3 TEAEs requiring dose reduction occur in cycle 1. The primary endpoints are objective response rate (ORR) at week 24 (ORR24W) and the proportion of pts with intolerable grade 2 and any grade ≥ 3 TEAEs within 24 wks after randomization. Secondary endpoints include PFS and ORR. An estimated 306 pts will be randomized. Sample size is based on detecting noninferiority (NI) of ORR24W and superiority of the primary safety endpoint. Two interim analyses (IA) will be performed when 150 and 200 pts have completed 24 wks of follow-up or discontinue earlier. Each analysis will test NI and futility of the LEN 14-mg arm ORR24W vs the 18-mg arm ORR24W. An O’Brien-Fleming boundary will be used for NI. If the 1-sided P-value is ≤ 0.005 at the first IA, ≤ 0.014 at the second IA, or ≤ 0.045 at the final analysis, then NI in ORR24W will be claimed. If the futility boundary is crossed (ie, 1-sided P-value is ≥ 0.776 at the first IA or ≥ 0.207 at the second IA), then futility will be claimed. Clinical trial information: NCT03173560.
Preparation and Characterization of a µ-P2O7-µ-HPO4 Dinuclear Fe2(III, III) Complex
Authors: Miyazato Yuji , Imaizumi Kouta , Tanaka Rikako , Wada Tohru , Matsushita Nobuyuki 
Published: February 2018

Abstract
The [{Fe(Me3tacn)}2(µ-P2O7)(µ-HPO4)]·12H2O dinuclear Fe2(III, III) complex was prepared. The HPO42− bridge in the complex arises from hydrolysis of the pyrophosphate bound to the Fe(III) centers in the trinuclear [{Fe(Me3tacn)}3(P2O7)2]+ intermediate. Electrochemical reduction of this complex at pH &lt;3.2 results in dissociation of the H2PO4− bridge.
Mainstreaming as rhetoric or reality? Gender and global health at the World Bank
Authors: Winters Janelle , Fernandes Genevie , McGivern Lauren , Sridhar Devi 
Published: February 2018

Background:Over the past decade gender mainstreaming has gained visibility at global health organisations. The World Bank, one of the largest funders of global health activities, released twoWorld Development Reportsshowcasing its gender policies, and recently announced a $1 billion initiative for women’s entrepreneurship. However, the development of the Bank’s gender policies and its financing for gender programmes have never been systematically analysed by external researchers in the context of global health. We use the Bank as a case study of how global health organisations frame their gender policies and measure their success.Methods:We constructed a timeline of the Bank’s governance of gender, through a review of published articles, grey literature, and Bank documents and reports. Additionally, we performed the first health-focused analysis of two publicly available Bank gender project databases, and tracked the Bank's financing of gender projects in the health sector from 1985-2017.Results:The Bank’s gender policy developed through four major phases from 1972-2017: ‘women in development’ (WID), institutionalisation of WID, gender mainstreaming, and gender equality through ‘smart economics’. In the more inclusive of the two Bank project databases, gender projects comprised between 1.3% (1985-1989) and 6.2% (2010-2016) of all Bank commitments, which is significantly less than the Bank’s claim that 98% of its lending is gender informed. Most funding targeted middle-income countries and particular themes, including communicable diseases and health systems. Major gender-related trust funds were absent from both databases.Conclusion:The Bank focused most of its health sector gender projects on women’s and girls’ issues. It is increasingly embracing private sector financing of its gender activities, which may impact its poverty alleviation agenda. Measuring the success of gender mainstreaming in global health will require the Bank and global health organisations to reconsider their use of gender indicators.
Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTRin Nociception
Authors: Sung Kijung , Ferrari Luiz F. , Yang Wanlin , Chung ChiHye , Zhao Xiaobei , Gu Yingli , Lin Suzhen , Zhang Kai , Cui Bianxiao , Pearn Matthew L. , Maloney Michael T. , Mobley William C. , Levine Jon D. , Wu Chengbiao 
Published: February 2018

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGFβ sequence (NGFR100W) in patients with hereditary sensory and autonomic neuropathy type V (HSAN V) made it possible to distinguish the signaling mechanisms that lead to two functionally different outcomes of NGF: trophic versus nociceptive. We performed extensive biochemical, cellular, and live-imaging experiments to examine the binding and signaling properties of NGFR100W. Our results show that, similar to the wild-type NGF (wtNGF), the naturally occurring NGFR100Wmutant was capable of binding to and activating the TrkA receptor and its downstream signaling pathways to support neuronal survival and differentiation. However, NGFR100Wfailed to bind and stimulate the 75 kDa neurotrophic factor receptor (p75NTR)-mediated signaling cascades (i.e., the RhoA-Cofilin pathway). Intraplantar injection of NGFR100Winto adult rats induced neither TrkA-mediated thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia based on agonism for TrkA signaling. Together, our studies provide evidence that NGFR100Wretains trophic support capability through TrkA and one aspect of its nociceptive signaling, but fails to engage p75NTRsignaling pathways. Our findings suggest that wtNGF acts via TrkA to regulate the delayed priming of nociceptive responses. The integration of both TrkA and p75NTRsignaling thus appears to regulate neuroplastic effects of NGF in peripheral nociception.SIGNIFICANCE STATEMENTIn the present study, we characterized the naturally occurring nerve growth factor NGFR100Wmutant that is associated with hereditary sensory and autonomic neuropathy type V. We have demonstrated for the first time that NGFR100Wretains trophic support capability through TrkA, but fails to engage p75NTRsignaling pathways. Furthermore, after intraplantar injection into adult rats, NGFR100Winduced neither thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia. We have also provided evidence that the integration of both TrkA- and p75NTR-mediated signaling appears to regulate neuroplastic effects of NGF in peripheral nociception. Our study with NGFR100Wsuggests that it is possible to uncouple trophic effect from nociceptive function, both induced by wild-type NGF.
Engineered cartilage tissue from biodegradable Poly(ε-caprolactone) scaffold and human umbilical cord derived mesenchymal stem cells
Authors: Nguyen Phuc Dang-Ngoc , Vu Ngoc Bich , Le Ha Thi-Ngan , Dao Thuy Thi-Thanh , Gia Long Xuan , Pham Phuc Van 
Published: February 2018

Introduction: Cartilage injury is the most common injury among orthopedic diseases. The predominant treatment for this condition is cartilage transplantation. Therefore, production of cartilage for treatment is an important strategy in regenerative medicine of cartilage to provide surgeons with an additional option for treatment of cartilage defects. This study aimed to produce in vitro engineered cartilage tissue by culturing and differentiating umbilical cord derived mesenchymal stem cells on biodegradable Poly(ε-caprolactone) (PCL) scaffold.
Methods: Human umbilical cord derived mesenchymal stem cells (UCMSCs) were isolated and expanded according to previous published protocols. UCMSCs were labeled with CD90 APC‑conjugated monoclonal antibody (CD90-APC) and then seeded onto porous PCL scaffolds. Cell adhesion and proliferation on PCL scaffolds were evaluated based on the strength/signal of APC, MTT assays, and scanning electron microscopy (SEM). The chondrogenic differentiation of UCMSCs on scaffolds was detected by Alcian Blue and Safranin O staining.
Results: The results showed that UCMSCs successfully adhered, proliferated and differentiated into chondroblasts and chondrocytes on PCL scaffolds. The chondrocyte scaffolds were positive for some markers of cartilage, as indicated by Alcian Blue and Safranin O staining.
Conclusion: In conclusion, this study showed successful production of cartilage tissues from UCMSCs on PCL scaffolds.
TILKA Educational Model and Nonviolent Communication
Authors: Mikolič Vesna 
Published: February 2018

The aim of the article is to present the development of the TILKA educational model. This new L1 and L2 teaching model integrates language and literature teaching through research and activity, as well as principles and methods of intercultural education and transactional analysis. Our main research question during the model development was how can nonviolent communication be included into the intercultural language teaching. The analysis of various discourses (science, tourism, politics, literature) with regard to intensity modification has shown that verbal aggressiveness can be related to the expression of intensity modification. Building the competence of nonviolent communication with the use of specific intensity modificators can be included into the language teaching model as one of the most important intercultural goals. Keywords: drama triangle; intensity modification; intercultural education; language and literature teaching; transactional analysis.
Historia del arrabal. Los bajos fondos bogotanos en los cronistas Ximénez y Osorio Lizarazo, 1924-1946
Authors: Reales Rizo María Del Pilar 
Published: February 2018

En el universo del arte pueden existir múltiples puntos de referencia para estimular una producción; muchas veces el elemento sugerente de una obra en el campo escénico, literario, plástico, o cinematográfico, proviene de factores inmersos en la realidad cotidiana, cuyo principio de intencionalidad llega al creador artístico bajo distintas incitaciones...
Pluralidade em tempo de cristianização: a concepção das identidades cristãs no Norte da África (200-450 d.C.)
Authors: Campos Ludimila Caliman 
Published: February 2018

Resenha de: REBILLARD, É. Christians and their many identities in Late Antiquity, North Africa, 200-450 CE. London: Cornell University Press, 2017. 144 p.
Greek student’s politicization: empirical research in schools of central Macedonia in Greece
Authors: Papaoikonomou Anthony D. 
Published: February 2018

This
paper presents a research that was carried out in schools of central Macedonia
in Greece about the degree of students’ politicization. The concept of
politicization was delineated using five different variables that describe
students’ way of thinking about different aspects of their reality. The
findings show that peer group was considered to be the most important
socializing factor which has a determining role in the political socialization
of students. The degree of politicization is equivalent with the attendance in
bars and the frequent watching of political programs on television.&nbsp; &nbsp;
Shallow Horizontal Well Cyclic Steam Stimulation in Clastic Unconsolidated Unconventional Reservoir in Kuwait - A Case Study
Authors: Al-Ballam Shaikha , Pandey Dharmesh Chandra 
Published: February 2018

Abstract
This paper presents the preliminary results of a Cyclic Steam Stimulation (CSS) trial in a horizontal well for the first time in the State of Kuwait.
The horizontal well was completed in a viscous crude oil bearing shallow unconsolidated sandstone reservoir of Middle Miocene age located in north of the State of Kuwait, in an area where currently several pilot projects are undergoing execution using mobile production facilities and permanent production facilities.
The drilling of the horizontal well was a challenge in terms of reservoir shallowness utilizing conventional drilling rig for vertical wells. The well was completed with 5" slotted liner sizes in an open hole section to prevent sand production and maintain hole stability. The artificial lift method deployed was high temperature tolerance All Metal Progressive Cavity Pumps (AMPCP). The well was equipped with unified Rod BOP which allow CSS operation without any intervention. The unified rod BOP reduces the nonproductive time (NPT) and oil deferment during the CSS process. Therefore, no need to change the X-Mass tree as the setup is applicable for injection and production phases.
The horizontal well started production for a short period of cold production phase followed by a Cyclic Steam Stimulation Cycle (CSS) for well productivity evaluation. The well's cold production, injection performance, production performance post CSS, and the AMPCP artificial lift performance shall be presented in this paper. Monitoring and surveillance detailed plans including nearby drilled observation wells were utilized in CSS performance assessment. The overall wells performance is showing encouraging and promising results for further optimization and field development.
Electrical Heating — Doing the Same Thing Over and Over Again …
Authors: Ali S. M. , Bayestehparvin B. 
Published: February 2018

Abstract
… And expecting different results. Electrical heating of oil reservoirs has fascinated petroleum engineers for more than 70 years - longer, if you include the use of heaters in Siberian oilfields. The earliest laboratory study was done in Pennsylvania in 1940's. Since then, many more studies and field tests have been carried out, none of which was a commercial success. This paper takes a look at different forms of electrical heating, the supporting theoretical work, and field tests. Additionally, several examples are given illustrating the limitations of electrical heating processes. Also discussed is the logic behind the resurgence of electrical heating in recent years. Not discussed are over 200 patents on electrical heating. The major electrical heating processes are resistance heating, using direct current or low frequency alternating current, induction heating, microwave heating, and heating by means of electrical heaters. These are described briefly, and compared. In applications to oil sands, the intent is to utilize the connate water as the heating element (resistance heating) or oil sands as the dielectric (microwave heating). Induction heating is much less effective but has been tested in many field projects. Shale that has a permeability of zero to fluid flow, is electrically conductive, and thus channels much of the electric current flow in resistance heating, which also has other limitations. Microwaves suffer from low depth of penetration (of the order of 20 cm in oil sands) and low power delivery (of the order of 1 MW as a maximum). The power requirements for a typical SAGD pair, in contrast, are 15-30 MW. Electric heaters have been used in oilfields for many years for near-wellbore heating. Two large field pilots used powerful electric heaters, and were recently shut down. Although electrical heating has not had commercial success, recently there has been a resurgence in various electrical processes, as a means of reducing GHG emissions, under the flawed logic that oilfield use of electricity would displace emissions caused by steam generation.