bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATOMIC-Meso: A randomized phase 2/3 trial of ADI-PEG20 or placebo with pemetrexed and cisplatin in patients with argininosuccinate synthetase 1-deficient non-epithelioid mesothelioma.
Authors: Szlosarek Peter Wojciech , Baas Paul , Ceresoli Giovanni Luca , Fennell Dean Anthony , Gilligan David , Johnston Amanda , Lee Phuong , Mansfield Aaron Scott , Nolan Luke , Nowak Anna K. , Steele Jeremy P. C. , Taylor Paul , Tsao Anne S. , Zauderer Marjorie Glass , Bomalaski John S. 
Published: September 2018

TPS8582 Background: Argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM) is sensitive to arginine deprivation therapy with pegylated arginine deiminase (ADI-PEG20), which also enhances the cytotoxicity of pemetrexed. The TRAP Phase 1 trial (NCT02029690) of ADI-PEG 20 combined with 1st-line pemetrexed (PEM) and cisplatin (CDDP) chemotherapy revealed a 94% disease control rate in non-epithelioid (biphasic and sarcomatoid) MPM subtypes characterized by a 75% rate of ASS1 loss. Thus, we plan to assess the efficacy of ADI-PEG20 or placebo combined with PEM and CDDP in patients (pts) with poor prognosis MPM in a randomized, placebo-controlled, double-blind phase 2/3 global trial. Methods: Up to 386 good performance (ECOG 0-1) pts with non-epithelioid malignant pleural mesothelioma will be enrolled in a phase 2/3 adaptive, biomarker-driven study design. Biopsies will be required prior to randomization: ASS1-agnostic pts will be enrolled initially (phase 2 stage) with an option to restrict enrolment to ASS1-deficient MPM (phase 3 stage). Pts will be randomized to receive weekly ADI-PEG20 (36 mg/m2 IM) or placebo with standard doses of PEM and CDDP for a maximum of 18 weeks (6 cycles) of treatment. Pts who develop CDDP toxicity may be switched to carboplatin. Pts will be assessed every 6 weeks using modified RECIST (RECIST 1.1 allowed for pts with significant extrathoracic disease). The primary endpoint for the phase 2 stage will be overall response rate (ORR) with secondary endpoints of overall survival (OS), safety and toxicity. The phase 2 will test ORR proportions with the placebo triplet set at 15% vs. 35% for the ADI-PEG 20 triplet, with a 1:1 randomization, 80% power. After recruitment of 176 pts, the phase 2 will convert to a phase 3 study with the primary endpoint of OS. In summary, ATOMIC-Meso is the first triplet chemotherapy study to assess the role of targeted arginine deprivation in aggressive subtypes of mesothelioma. Pt accrual has commenced across the US and Asia, with enrolment due in Europe and Australia by 2nd quarter of 2017. [Trial sponsored by Polaris Group]. Clinical trial information: NCT02709512.
A phase III study of rovalpituzumab tesirine maintenance therapy following first-line platinum-based chemotherapy in patients with extensive disease small cell lung cancer (ED SCLC).
Authors: Komarnitsky Philip B. , Lee Ho-Jin , Shah Manan , Wong Shekman , Gauthier Sanja , Dziubinski Juliann , Osbaugh Stacy , Zhang Fan 
Published: September 2018

TPS8583 Background: SCLC embodies 15-20% of lung cancers. Patients (pts) are staged with either limited or extensive disease; the standard front-line treatment for the latter is chemotherapy with carbo- or cisplatin combined with etoposide or irinotecan. Response rates are high with limited duration. Recurrence may be attributable to chemo-resistant tumor initiating cells (TICs). Delta-like protein 3 (DLL3) is an inhibitory Notch receptor ligand identified as a novel target in SCLC TICs. DLL3 is highly expressed in SCLC but not normal tissue. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a DNA cross-linking toxin. Rova-T has shown activity in recurrent/relapsed ED SCLC patients (Rudin et al., Lancet Oncol, 2016). Given DLL3 expression in TICs, exploration of Rova-T front-line maintenance strategies in ED SCLC is warranted. The postulated mechanism of action of Rova-T and its clinical activity indicate potential to improve progression-free and overall survival in this setting. Methods: This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no pts enrolled yet as of 7 February 2017). Approximately 740 ED SCLC pts will be enrolled to include ~480 pts with high DLL3 expression. Eligibility: pts ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1st line platinum-based therapy; definitively treated CNS metastases allowed; > 3 but ≤ 9 wks between the administration of the last cycle of platinum-based chemotherapy and randomization; available tumor tissue for DLL3 expression testing; ECOG performance score 0-1. Pts will be randomly assigned 1:1 to receive 0.3 mg/kg Rova-T or placebo on Day 1 of each 6-wk cycle, omitting every 3rd cycle. Primary objectives: determine if Rova-T improves progression-free and overall survival. Secondary objectives: assess Rova-T antitumor activity by determining objective response rate, clinical benefit rate, duration of response, and changes in pt reported outcomes. Clinical trial information: NCT03033511.
IMpower132: A phase III clinical program—1L atezolizumab plus platinum-based chemotherapy in chemo-naive advanced non-squamous NSCLC.
Authors: West Howard Jack , Nishio Makoto , Dols Manuel Cobo , Saito Haruhiro , Howland Michael , Hoang Tien , Asakawa Takashi , Sandler Alan , Socinski Mark A. 
Published: September 2018

TPS9101 Background: Platinum-based chemotherapy (chemo) is the current standard of care for patients (pts) with newly diagnosed advanced non-squamous NSCLC. The combination of platinum-based chemo and pemetrexed (pem) provides comparable benefit to pts as other standard platinum doublets commonly used and has a favorable toxicity profile. However, the survival benefit conferred by this combination leaves considerable room for improvement. The anti–PD-L1 mAb atezolizumab (atezo) inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. In the OAK trial, pts with 2L/3L advanced NSCLC had improved mOS in the atezo arm (13.8 mo) vs the docetaxel arm (9.6 mo), with a survival benefit observed across PD-L1 expression levels. The potential for chemo to further augment responses to atezo, with tolerable safety, has also been demonstrated. A global, Phase III, randomized, open-label trial, IMpower132 (NCT02657434), is being conducted to evaluate 1L atezo + platinum-based chemo + pem in chemo-naive pts with stage IV NSCLC. Methods: Eligibility criteria include stage IV NSCLC, measurable disease (RECIST v1.1), no prior chemo and ECOG PS 0-1. Exclusion criteria include tumors known to harbor EGFR or ALK driver mutations, untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Pts will be enrolled regardless of PD-L1 expression status and randomized to the treatment arms. Pts will be stratified by sex, ECOG PS, type of chemo (carboplatin [carbo] vs cisplatin [cis]) and smoking status. Pts will receive four or six 21-day cycles of either atezo + carbo/cis + pem or carbo/cis + pem. Following the induction phase, pts will receive maintenance atezo + pem or pem alone, depending on their allocated treatment regimen. Pts receiving atezo may continue until loss of clinical benefit.Co-primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include IRF-assessed PFS, investigator-assessed ORR and safety. Predictive biomarkers associated with efficacy will be evaluated. Approximately 568 pts will be enrolled. Clinical trial information: NCT02657434.
Pembrolizumab with or without vismodegib in treating metastatic or unresectable basal cell skin cancer.
Authors: Chang Anne Lynn S. , Tran Duy C , Brotherton Richard , Reddy Sunil , Colevas A. Dimitrios 
Published: September 2018

TPS9593 Background: Basal cell carcinomas (BCCs) are the most common cancer in humans and have increased > 75% in the past two decades, with > 28,000 cases of advanced or metastatic diseases per year. Targeted therapy in the form of Smoothened inhibitors (SIs) are FDA approved for advanced BCC, however, over half of patients do not respond or become resistant to SI monotherapy after initial response. At this time, there are no other FDA approved drugs for advanced BCCs, however, emerging data indicates that a significant proportion of BCCs express programmed cell death ligand (PD-L)-1, suggesting potential response to PD-1 inhibition. In addition, BCCs are keratinocytic tumors, and our case series of PD-1 inhibitors against cutaneous squamous cell carcinomas, another keratinocytic tumor, have shown activity. Here, we present a proof-of-principle, phase 1b, open-label investigator initiated study of pembrolizumab for unresectable or metastatic BCC (NCT02690948). Methods: Following institutional review board approval, patients with locally advanced or metastatic BCCs who met all eligibility criteria were enrolled at a single academic center. Participants were allocated into either Arm 1 (pembrolizumab 200 mg IV every 3 weeks) or Arm 2 (pembrolizumab 200 mg IV every 3 weeks and concurrent vismodegib 150 mg by mouth daily) until disease progression or intolerable toxicity. Major inclusion criteria include individuals aged > or = 18 years with histologically verified unresectable and/or metastatic BCC, and with measurable disease by Response Evaluation Criteria for Solid Tumors version 1.1. Exclusion criteria include immunosuppresion, active infection, history of pneumonitis and autoimmune disease requiring systemic treatment. The primary outcome measures are the overall response rates in Arm 1 and 2. Secondary outcome measures include incidence and severity of adverse events (AEs) as defined by the Common Terminology Criteria for Adverse Events verson 4.0, and progression free survival. This study is currently enrolling, with 10 of 26 patients accrued to date (6 of 13 in Arm 1; 4 of 13 in Arm 2), and the study stopping rule (based on first 10 enrolled patients displaying progressive disease) did not need to be deployed. Clinical trial information: NCT02690948.
Multi-center phase Ib study of intermittent dosing of the MEK inhibitor, selumetinib, in patients with advanced uveal melanoma not previously treated with a MEK inhibitor.
Authors: Komatsubara Kimberly Mayumi , Shoushtari Alexander Noor , Patel Sapna Pradyuman , Momtaz Parisa , Singh-Kandah Shahnaz , Carter Amanda , Cain Suzanne , Taiclet Lauren , DeNoble Sarah , Negri Tiffany , Lacey Danielle , Ambrosini Grazia , Lee Shing Mirn , Schwartz Gary K. , Carvajal Richard D. 
Published: September 2018

TPS9597 Background: Uveal melanoma (UM) is a rare subtype of melanoma with no effective therapy for advanced disease. UM is characterized by mutations in GNAQ and GNA11 leading to constitutive activation of the mitogen activated protein kinase (MAPK) pathway. We have previously shown that targeting the MAPK pathway though MEK inhibition with Selumetinib (AZD6244, ARRY-142886) using a continuous dosing schedule improved progression free survival (PFS) in a randomized Phase II study of Selumetininb versus chemotherapy in patients with metastatic UM; however, no PFS or overall survival (OS) benefit was observed in a subsequent randomized Phase III study of Selumetinib and chemotherapy versus chemotherapy alone. We hypothesize that an intermittent dosing schedule of Selumetinib may be more effective than continuous dosing by achieving higher dose levels, better drug tolerability, and more complete target inhibition. We propose a Phase Ib study of Selumetinib in UM using an intermittent dosing schedule. Methods: A total of 28 subjects will be enrolled using the time to event continual reassessment method (TITE-CRM). Key inclusion criteria include a diagnosis of advanced UM, measurable disease by RECIST v1.1, and no prior MEK inhibitor therapy. Eligible subjects will be treated with Selumetinib starting at a dose level of 125 mg orally twice a day, using a 3-days-on and 4-days-off per week schedule. The primary goal of this study is to estimate the maximum tolerated dose (MTD) of intermittently dosed Selumetinib. Secondary endpoints are response rate, PFS and OS. Responses will be evaluated every 8 weeks by a CT scan of the chest and CT or MRI of the abdomen/ pelvis using RECIST v1.1 criteria. Mandatory tumor biopsies will be obtained at baseline, cycle 1 day 3 (Selumetinib-on day), and between cycle 1 day 11-14 (Selumetinib-off day) in 20 subjects, and optionally at progression. Tumor tissue will be assessed for MAPK pathway inhibition and reactivation at each time point, as well as mechanisms of resistance. Recruitment is currently ongoing. Clinical trial information: NCT02768766.
ОЦЕНКА СОЦИАЛЬНО-ЭКОНОМИЧЕСКОЙ ПЕРСПЕКТИВНОСТИ ПРЕДПРИЯТИЙ СЕВЕРНЫХ РЕГИОНОВ РОССИИ
Authors: Zhukov Maksim Yur’evich , Globa Svetlana Borisovna 
Published: September 2018

Проведен анализ существующей методологии и инструментов мониторинга развития экономических систем. Рассмотрены особенности развития Северных регионов. Обоснована необходимость совершенствования системы мониторинга и управления развитием Северных регионов. Предложено применения критерия социально-экономическая перспективность, разработаны методологические рекомендации и инструменты для его оценки. Проведен анализ отличий социально-экономической перспективности и инвестиционной привлекательности. Произведена оценка социально-экономической перспективности ПАО «НОВАТЭК».Цель – совершенствование методологического аппарата мониторинга и управления развитием социально-экономических систем Северных регионов.Метод или методология проведения работы: в статье использовались экономико-математические, статистические, общенаучные методы анализа.Результаты: разработаны рекомендации по совершенствованию методологического аппарата мониторинга и управления развитием социально-экономических систем Северных регионов. Установлена взаимосвязь экологической безопасности и инновационной деятельности газодобывающих компаний.Область применения результатов: полученные результаты целесообразно применять в управлении предприятиями, инвесторам, органам государственной власти, региональным властям Северных территорий.
Communication with health professionals: The views of pregnant women with a raised BMI
Authors: Cunningham Jenny , Endacott Ruth , Gibbons Dinah 
Published: September 2018

Background There is evidence that midwives may find discussions about weight difficult with pregnant women with a raised body mass index (BMI). In previous studies, pregnant women have reported a lack of information and negative experiences. Aim To explore the experiences of pregnant women with a raised BMI to investigate if their pregnancies were affected by their interactions with midwives and other health professionals. Methods Women (n=11) were interviewed using an standardised framework. The discussions were recorded and then transcribed. Thematic analysis was used. Findings Three themes emerged from the data: ‘feeling judged’, ‘knowledge gap’ and ‘doing your best’. Conclusion Pregnant women with a raised BMI can feel judged in their communications with midwives and other health professionals. They do not have the information necessary to make informed decisions on their care but they do their best to follow guidelines and have a healthy pregnancy.
Optimization of the extraction of natural phenolic antioxidants from the seeds of Tamarindus indica L. - an undervalued by product of food processing - using response surface methodology
Authors: Sarkar Atreyi , Ghosh Uma 
Published: September 2018

The seeds of Tamarindus indica are known to possess a wide range of phenolic compounds with high antioxidant activity as measured by the ferric reducing antioxidant power (FRAP). In the present study, the optimum conditions for the extraction of crude phenolic antioxidants from Tamarind seed were determined using response surface methodology (RSM). A central composite design (CCD) was used to investigate the effects of four independent variables, namely concentration of extractable solids in solvent (g/ml; X1), extraction time (h; X2), extraction temperature (°C; X3) and solvent concentration (%, v/v; X4) on the responses of total polyphenol content (TPC) and FRAP. The CCD consisted of 30 experimental runs. A second-order polynomial model was used for predicting the responses. Canonical analysis of the surface responses revealed that the predicted optimal conditions for the maximal yield of TPC and FRAP were concentration of extractable solids in solvent of 0.049 g/ml, extraction time of 3.24 h, extraction temperature of 45 °C and a solvent concentration of 50%. The experimental values in the optimised condition coincided with the predicted ones within a 95% confidence interval, hence indicating the suitability of the model and the success of RSM in optimizing the extraction parameters.
Die Krux mit Zielkonflikten
Authors: Dusseldorp Marc 
Published: September 2018

Das Integrative Konzept nachhaltiger Entwicklung zählt zu den prominentesten Ansätzen zur Operationalisierung des Nachhaltigkeitsleitbilds im deutschsprachigen Raum. Seit seiner Entwicklung um die Jahrtausendwende ist es in zahlreichen Projekten angewandt worden und hatte somit eine beträchtliche Reichweite. Eine kritische Analyse und Revision des Konzepts steht indes noch aus – was nicht zuletzt mit Blick auf die bestehenden Anwendungsprobleme Not täte. Hierzu möchte der vorliegende Artikel einen Beitrag leisten. Dabei zeigt sich, dass die Analyse des Integrativen Nachhaltigkeitskonzepts auch wichtige Impulse für die Nachhaltigkeitsdebatte im Allgemeinen und für den Umgang mit Zielkonflikten im Besonderen zu geben vermag. Insbesondere wird deutlich, dass das Nachhaltigkeitsleitbild mittels (nicht abwägbarer) Satisfizierungsnormen zu operationalisieren ist: Nur diese sind dazu geeignet, die Entwicklung hinreichend wirksamer Maßnahmen zur Realisierung einer nachhaltigen Entwicklung anzuleiten.
Optimal Auxiliary Functions Method for viscous flow due to a stretching surface with partial slip
Authors: Marinca Vasile , Ene Remus-Daniel , Marinca Valentin Bogdan 
Published: September 2018

AbstractThe viscous flow induced by a stretching surface with partial slip is investigated. The flow is governed by a third-order nonlinear differential equation, corresponding to the planar and axisymmetric stretching. The derived equation of motion is solved analytically by Optimal Auxiliary Functions Method (OAFM). This procedure is highly efficient and it controls the convergence of the approximate solution. A few examples are given, showing the exceptionally good agreement between the analytical and numerical solutions of the nonlinear problem. OAFM is very efficient in practice, ensuring a very rapid convergence after only one iteration.
UV and Solar Light Induced Natural Iron Oxide Activation: Characterization and Photocatalytic Degradation of Organic Compounds
Authors: Belaidi S. , Mammeri L. , Mechakra H. , Remache W. , Benhamouda K. , Larouk S. , Kribeche M. A. , Sehili T. 
Published: September 2018

Abstract
In this study we demonstrate the efficiency of a natural mineral as a photocalyst. This natural mineral was provided from the iron ore deposit from Chaabet-El-Ballout which is located in North-East of Algeria. The characterization analysis of the mineral by the Energy-dispersive X-ray spectroscopy (EDX) revealed that the natural powder has a mixed elemental composition and consist mainly of iron oxide with 50 % of iron. In order to determine the crystal phase composition of the natural iron oxide (NIO), X-ray diffraction (DRX) measurement and infrared absorption spectroscopy (FTIR) were carried out. The results showed that the NIO has a mixed crystal structure composed mainly of hematite and lesser extent of goethite. The specific surface area and the total pore volume of the NIO were 79.015 m2g−1 and 0.0892 cm3g−1 respectively, measured by the Brunauer Emmett–Teller method (BET). The Raman spectrum of the NIO confirmed that the sample has seven characteristic peaks attributable to hematite. The optical properties of soil powder were examined by UV-vis diffuse reflectance spectroscopy (DRS). The pH of point of zero charge (pHpzc) of the adsorbent was determined, a value of 8.3 was found. The photocatalytic activity of the NIO particles was tested by the decomposition of aqueous solution of different class of compounds; phenolic compounds, pesticides and dyes due to their presence in many types of wastewaters. The sorption on the surface of the NIO with photocatalytic oxidation using oxalic acid and hydrogen peroxide would be an effective oxidation process for the removal of contaminants under UV and solar irradiation. High percentages of degradation of 1- Naphtol (1-NP) and Linuron were found about, 94.6 %, 97.2 % respectively, in presence of NIO and H2O2 under UV irradiation. The presence of oxalic acid with NIO enhanced the photodegradation of 2,6-dimethylphenol (2,6-DMP), 2-chlorophenol (2-CP) and Methylene blue (MB) with 72 %, 92 % and 100 % percentages of degradation respectively.
BioModelKit – An Integrative Framework for Multi-Scale Biomodel-Engineering
Authors: Blätke Mary-Ann 
Published: September 2018

Abstract
While high-throughput technology, advanced techniques in biochemistry and molecular biology have become increasingly powerful, the coherent interpretation of experimental results in an integrative context is still a challenge. BioModelKit (BMK) approaches this challenge by offering an integrative and versatile framework for biomodel-engineering based on a modular modelling concept with the purpose: (i) to represent knowledge about molecular mechanisms by consistent executable sub-models (modules) given as Petri nets equipped with defined interfaces facilitating their reuse and recombination; (ii) to compose complex and integrative models from an ad hoc chosen set of modules including different omic and abstraction levels with the option to integrate spatial aspects; (iii) to promote the construction of alternative models by either the exchange of competing module versions or the algorithmic mutation of the composed model; and (iv) to offer concepts for (omic) data integration and integration of existing resources, and thus facilitate their reuse. BMK is accessible through a public web interface (www.biomodelkit.org), where users can interact with the modules stored in a database, and make use of the model composition features. BMK facilitates and encourages multi-scale model-driven predictions and hypotheses supporting experimental research in a multilateral exchange.
A gradient theory based on the Aifantis theory using the Gurtin-Anand strain gradient plasticity approach
Authors: Borokinni Adebowale S. 
Published: September 2018

AbstractThis article investigates the differences between the Aifantis and Gurtin-Anand strain gradient plasticity. The fact that Gurtin-Anand strain gradient plasticity is richer than the Aifantis strain gradient plasticity provides a basis for which we could derive equivalent Aifantis flow rule and extend it to accommodate scalar dissipative hardening. It was found that the major difference between the Gurtin-Anand and Aifantis theories lies on the use of the codirectionality hypothesis and constraint imposed on the gradient of the flow direction.