bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study
Authors: Garon Edward B. , Hellmann Matthew D. , Rizvi Naiyer A. , Carcereny Enric , Leighl Natasha B. , Ahn Myung-Ju , Eder Joseph Paul , Balmanoukian Ani S. , Aggarwal Charu , Horn Leora , Patnaik Amita , Gubens Matthew , Ramalingam Suresh S. , Felip Enriqueta , Goldman Jonathan W. , Scalzo Cathie , Jensen Erin , Kush Debra A. , Hui Rina 
Published: June 2019

PURPOSE Pembrolizumab monotherapy has demonstrated durable antitumor activity in advanced programmed death ligand 1 (PD-L1)–expressing non‒small-cell lung cancer (NSCLC). We report 5-year outcomes from the phase Ib KEYNOTE-001 study. These data provide the longest efficacy and safety follow-up for patients with NSCLC treated with pembrolizumab monotherapy. PATIENTS AND METHODS Eligible patients had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by immunohistochemistry using the 22C3 antibody. Patients received intravenous pembrolizumab 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks. Investigators assessed response per immune-related response criteria. The primary efficacy end point was objective response rate. Overall survival (OS) and duration of response were secondary end points. RESULTS We enrolled 101 treatment-naive and 449 previously treated patients. Median follow-up was 60.6 months (range, 51.8 to 77.9 months). At data cutoff—November 5, 2018—450 patients (82%) had died. Median OS was 22.3 months (95% CI, 17.1 to 32.3 months) in treatment-naive patients and 10.5 months (95% CI, 8.6 to 13.2 months) in previously treated patients. Estimated 5-year OS was 23.2% for treatment-naive patients and 15.5% for previously treated patients. In patients with a PD-L1 tumor proportion score of 50% or greater, 5-year OS was 29.6% and 25.0% in treatment-naive and previously treated patients, respectively. Compared with analysis at 3 years, only three new-onset treatment-related grade 3 adverse events occurred (hypertension, glucose intolerance, and hypersensitivity reaction, all resolved). No late-onset grade 4 or 5 treatment-related adverse events occurred. CONCLUSION Pembrolizumab monotherapy provided durable antitumor activity and high 5-year OS rates in patients with treatment-naive or previously treated advanced NSCLC. Of note, the 5-year OS rate exceeded 25% among patients with a PD-L1 tumor proportion score of 50% or greater. Pembrolizumab had a tolerable long-term safety profile with little evidence of late-onset or new toxicity.
Comprehensive Organizational and Methodical Approaches to Decommissioning of Radwaste Repositories
Authors: Майзик А. , Mayzik A. , Кореньков И. , Korenkov I. , Цовьянов А. , Tsoviyanov A. , Лащенова T. , Laschenova T. , Клочков В. , Klochkov V. 
Published: June 2019

Purpose: Development of comprehensive organizational and methodical approaches to decommissioning of shallow radwaste (RW) repositories.
Material and methods: The following researches were conducted during assessment of radiation and hygiene situation:
- assessing the state of physical barriers of repositories (tanks) of solid and liquid RW;
- assessing radiation situation at the repository site before and after remediation;
- measuring specific activity of 90Sr and 137Cs in ground and subsurface water, core sample, soils, building structures.
Methods: on foot gamma survey; gamma-ray spectrometric measurement of radionuclides in environmental samples using a stationary spectrometer; radiochemical extraction of radionuclides and their radiometry.
Results: The surveys were performed in 2014–2016. They delivered data on gamma dose rate at the RW repository site, specific activity of 90Sr and 137Cs in ground and subsurface water, core sample, soils, building structures.
The surveys showed that content of 90Sr in subsurface water varied from 0.25 to 0.4 Bq/kg, while content of 137Cs was below the detection threshold (0.01 Bq per sample). It was founded that distribution of 90Sr and 137Cs in soil (core sample) forming the top layer of the area is highly uneven. In some cases specific activity of soil exceeded 1000 Bq/kg (C-23 well at the depth of 2.75 m and C-24 well at the depth of 5 m). In all other cases specific activity of the core sample did not exceed 10 Bq/kg, and specific activity of soil was up to 50 Bq/kg which is over background values. The ambient dose equivalent rate at the site varied from 0.1 to 0.3 µSv/h.
After remediation activities content of radionuclides in soil and subsurface water was at the levels of background values.
More than 6700 measurements were performed (more than 2400 measurements of the ambient dose equivalent rate, more than 4100 measurements of beta-contamination of work surfaces and equipment, and more than 200 measurements of specific and volumetric activity of environmental samples).
Conclusions: This work allowed to substantiate technical solutions, procedure of RW accounting and control, using of shelters and mobile systems for radiation safety of the personnel and environmental protection.
It was demonstrated that average external radiation doses for the workers involved in decommissioning activities did not exceed 0.7 mSv (variation from 0.16 to 1.7 mSv), while internal radiation doses varied from 0.35 to 3.3 µSv.
Density of beta-contamination of the site did not exceed 38 beta-particles/(cm2∙min) which corresponds to background values. The ambient dose equivalent rate of the site was within 0.09-0.15 µSv/h after the work has been done.
Calculation of the Depth Dependence of Relative Biological Effectiveness For Clinical Proton Beams
Authors: Белоусов А. , Belousov A. , Бахтиозин Р. , Bahtiosin R. , Колыва­нова М. , Kolyvanova M. , Крусанов Г. , Krusanov G. , Шулепова Л. , Shulepova L. , Морозов В. , Morozov V. 
Published: June 2019

Purpose: Accurate establishing the value of relative biological effectiveness (RBE) for high energy protons is one of the main challenges of modern radiotherapy. The purpose of the study is to calculate the depth dependence of RBE for proton beams forming a spread-out Bragg peak.
Material and methods: Spatial distributions of absorbed dose and dose-average linear energy transfer (LET) for 50-100 MeV (0.5 MeV energy step) monochromatic proton beams were obtained by Monte-Carlo computer simulation using Geant4 software. A linear dependence of RBE on the dose-average LET was used. Absorbed dose distributions were obtained in a water phantom for monochromatic pencil proton beams of 2.5 mm radius. The absorbed dose and the dose-average LET values were calculated in voxels with dimensions of 2×2×0.2 mm.
Results: Calculations of depth dependencies of absorbed dose and dose-average LET for 50–100 MeV monochromatic proton beams were performed. Depth dependencies of RBE for these beams were established. The weighing coefficients values allowing to generate uniformspread-out Bragg peak (SOBP) were determined. Depth distribution of “RBE-weighted” dose and RBE values for SOBP were found.
Conclusion: The impact of the initial beam energy step on the degree of homogeneity of the modified Bragg curve was investigated. It was shown that a step up to 1.5 MeV is acceptable for generate a smooth Bragg curve. The depth dependence of the average RBE value is a complex function, which rapidly changes especially at the far end of the SOBP. RBE may vary up to 10-30 % compared to current clinical value. The linear model of RBE-LET dependence shown in the study can be easily used in dosimetric planning systems, that may will significantly improve the quality of proton radiotherapy.
Prospects of Proton Therapy Combined Technologies in the Treatment of Cancer
Authors: Бушманов Андрей , Bushmanov Andrey , Шейно И. , Sheino I. , Липенгольц А. , Lipengolts A. , Соловьев А. , Solovev A. , Корякин С. , Koryakin S. 
Published: June 2019

Purpose: Evaluating the possibilities to increase proton radiotherapy therapeutic efficacy by means of combined (binary) technologies: simultaneous application of proton radiation and special drugs.
Material and methods: Published studies assessing antitumor efficacy of proton radiation together with simultaneous tumor radiosensitizing chemical compounds administration in treating cancer are being reviewed and analyzed.
Results: Two approaches to increase therapeutic efficacy of proton radiotherapy using drugs, which have abnormally large value of proton interaction cross section comparing to soft tissues, can be outlined recently. They are: 1) utilization of proton induced nuclear reactions producing high LET secondary radiation to increase absorbed dose in tumor; 2) utilization of protons and proton track’s secondary electrons interaction with high-Z nanoparticles (Z>52), that leads to redistribution of released proton energy in soft tissues and its localization in tumor volume.
Limited number of the studies devoted to application of 11B(p,3a) nuclear reaction in proton therapy and contradictoriness of the obtained result do not allow to judge so far about the future prospects of the boron containing drugs utilization in proton therapy to increase its antitumor efficacy. However, this approach looks very attractive because of the already existing boron drugs successfully being applied in boron neutron capture therapy. Analysis of the metal nanoparticle application in radiotherapy showed that despite of the promising results showing impressive tumor suppression increase represented in many scientific papers only three pharmaceuticals based on nanoparticles reached Phase I/II Clinical Trials. Radiosensitizing mechanism of metal nanoparticles in radiotherapy is still unrevealed, unstudied and not formalized thus interfering nanoparticle based pharmaceuticals to be approved for Clinical Trials. Quantitative relationship between nanoparticles’ properties (i.e. chemical composition, shape, surface coating etc.), irradiation parameters and final biological effect (therapeutic efficacy) is still undetermined.
Conclusion: Fundamental and applied studies should be carried out to determine and describe the processes underlying in the basis of combined methods of proton radiotherapy. That would allow to perform both proper treatment planning, similar to conventional radiotherapy, as well as the prognosis of the therapy final outcomes in curing malignant tumors.
Total knee arthroplasty after distal femoral osteotomy long-term survivorship and clinical outcomes
Authors: Chalmers B. P. , Limberg A. K. , Athey A. G. , Perry K. I. , Pagnano M. W. , Abdel M. P. 
Published: June 2019

AimsThere is little literature about total knee arthroplasty (TKA) after distal femoral osteotomy (DFO). Consequently, the purpose of this study was to analyze the outcomes of TKA after DFO, with particular emphasis on: survivorship free from aseptic loosening, revision, or any re-operation; complications; radiological results; and clinical outcome.Patients and MethodsWe retrospectively reviewed 29 patients (17 women, 12 men) from our total joint registry who had undergone 31 cemented TKAs after a DFO between 2000 and 2012. Their mean age at TKA was 51 years (22 to 76) and their mean body mass index 32 kg/m2(20 to 45). The mean time between DFO and TKA was ten years (2 to 20). The mean follow-up from TKA was ten years (2 to 16). The prostheses were posterior-stabilized in 77%, varus-valgus constraint (VVC) in 13%, and cruciate-retaining in 10%. While no patient had metaphyseal fixation (e.g. cones or sleeves), 16% needed a femoral stem.ResultsThe ten-year survivorship was 95% with aseptic loosening as the endpoint, 88% with revision for any reason as the endpoint, and 81% with re-operation for any reason as the endpoint. Three TKAs were revised for instability (n = 2) and aseptic tibial loosening (n = 1). No femoral component was revised for aseptic loosening. Patients under the age of 50 years were at greater risk of revision for any reason (hazard ratio 7; p = 0.03). There were two additional re-operations (6%) and four complications (13%), including three manipulations under anaesthetic (MUA; 10%). The Knee Society scores improved from a mean of 50 preoperatively (32 to 68) to a mean of 93 postoperatively (76 to 100; p < 0.001).ConclusionA cemented posterior-stabilized TKA has an 88% ten-year survivorship with revision for any reason as the endpoint. No femoral component was revised for aseptic loosening. Patients under the age of 50 years have a greater risk of revision. The clinical outcome was significantly improved but balancing the knee was challenging in 13% of TKAs requiring VVC. Overall, 10% of TKAs needed an MUA, and 6% of TKAs were revised for instability. Cite this article: Bone Joint J 2019;101-B:660–666.
The HINTEGRA total ankle arthroplasty
Authors: Yang H-Y , Wang S-H , Lee K-B 
Published: June 2019

Aims The purpose of this study was to determine the functional outcome and implant survivorship of mobile-bearing total ankle arthroplasty (TAA) performed by a single surgeon. Patients and Methods We reviewed 205 consecutive patients (210 ankles) who had undergone mobile-bearing TAA (205 patients) for osteoarthritis of the ankle between January 2005 and December 2015. Their mean follow-up was 6.4 years (2.0 to 13.4). Functional outcome was assessed using the Ankle Osteoarthritis Scale, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, 36-Item Short-Form Health Survey (SF-36) score, visual analogue scale, and range of movement. Implant survivorship and complications were also evaluated. Results There were significant improvements in all functional outcome categories between the preoperative and final follow-up assessments (p < 0.001). Patients showed marked improvement in clinical outcomes in terms of pain, function, and quality of life. The overall implant survivorship was 91.7% at a mean follow-up of 6.4 years. In all, 33 major complications were identified with a 15.7% rate, resulting in 12 prosthesis failures (5.7%). Periprosthetic osteolysis (19 cases; 9.0%) was the most frequent complication. Conclusion Mobile-bearing TAA resulted in improved functional outcomes, a low major complication rate, and excellent implant survivorship at a mean follow-up of 6.4 years. Cite this article: Bone Joint J 2019;101-B:695–701.
Book Reviews
Authors: Visser Renske , O’Connor Kaori , Korstanje Maximiliano E. 
Published: June 2019

Dying to Eat: Cross-Cultural Perspectives on Food, Death, and the Afterlife, Candi K. Cann (ed.) (2017) Lexington: University Press of Kentucky, 208 pp., ISBN 978-0-81317-471-6, h/bk, $65.00
Royal Events: Rituals. Innovations, Meanings Jennifer Laing and Warwick Frost (2018) Abingdon: Routledge, xi + 250 pp., ISBN 978-1-13811-981-9, h/bk, £105
An Anthropological Study of Hospitality: The Innkeeper and the Guest, Amitai Touval (2017) New York, Palgrave Macmillan, 88 pp., ISBN 978-3-31942-049-3, h/bk, £49.00
O papel dos Conselhos de Educação no Brasil / The role of the Education Councils in Brazil
Authors: Costa Esmeralda Maria De Oliveira , Fanego Graciela 
Published: June 2019

O objetivo do presente estudo foi discutir o papel dos conselhos escolares à luz do controle social. A formação dos Conselhos Municipais de Educação, devem implicar em uma maior autonomia, nas decisões referentes a educação municipal. Contudo, muitos desses Conselhos, criados no afã de cumprir a legislação, não parecem terem atentado para a importância de articular os profissionais da educação, alunos, pais e a comunidade, juntamente com o poder executivo, de forma a elaborarem um planejamento estratégico que possa garantir seu efetivo funcionamento (dos Conselhos). Os resultados demonstraram que o processo de conquista da autonomia pelos Conselhos acontece em meio a controvérsias, os Conselhos estão ainda a passos lentos para exercer a gestão democrática nas políticas públicas de educação, porém simbolizam um lugar favorável para a participação da sociedade e o controle social mais legítimo, sendo sem dúvida a direção certa para que se alcance uma educação de qualidade.
Theoretical proposal of steps for the implementation of the Industry 4.0 concept
Authors: Cordeiro Gabrielly Araújo , Ordóñez Robert Eduardo Cooper , Ferro Rodrigo 
Published: June 2019

Goal: The purpose of this paper is to present a proposal of steps for the implementation of Industry 4.0 in the industrial context, considering management and operational aspects. The reason is to discuss that technological change is accompanied by many organizational implications, in which it is perceivable that some companies already experience strategic and operational turbulence due to the lack of understanding of the this structure’s complexity.
Design / Methodology / Approach: This study assumes an exploratory character because the subject of analysis is still in the knowledge-structuring phase. In this sense, data was collected from the literature review.
Results: A theoretical proposal for the Industry 4.0 implementation framework is presented in flow format. It is organized in steps that cover the strategic and operational aspects during the implementation flow.
Limitations of the investigation: The limitations of this study are directly related to its theoretical nature and the difficulty of finding tools that help in the execution of each proposed stage.
Practical implications: However, based on theoretical insights, a trajectory of a transformation model is proposed, thus this research intends to show clearly and direct how companies can introduce the aspects of Industry 4.0 to their own benefit.
Originality / Value: In this study, a conceptual model is structured, and it indicates a potential of application because it contributes to support and encourage the adoption of technologies and concepts indicated in the Industry 4.0 literature in a structured way.
Makerspace for skills development in the industry 4.0 era
Authors: Dos Santos Eduardo Ferro , Benneworth Paul 
Published: June 2019

Goal / Purpose: Universities are increasingly investing in makerspaces. These learning spaces are presented as a place where students can share their projects, can innovate using rapid prototyping equipment, use low and high technology that serves as a starting point for students to launch start-ups, get advice on how to place a product in the market, and relate to potential lenders. This paper aims to discuss whether companies can benefit from these projects and whether skills for engineers can be developed in this environment. The paper provides insightful perceptions of the actions developed by one emergent university to develop innovative methodologies to support industry and students, to provide potential partnerships that fund projects in order to better prepare professionals for the industry 4.0.
Design / Methodology / Approach: A discussion of the subject was carried out based on the existing literature and an exploratory study in an existing makerspace in the Netherlands. It was one qualitative research based on a case study. Field observation and research questions were based on the technical skills of engineering described in theory.
Results: This article presented the idea that the makerspaces can be a great source of innovation if they are appropriately designed. The connection between universities and companies, aligned to active methodologies for teaching and learning meets a global need within a corporate universe to get faster and simpler and make the team see the project in a more holistic and complete manner. However, the goal is to bridge the gap with professors, researchers, makers, start-ups, and companies who want to use business-to-business practices. It can be said that these are beneficial characteristics of a makerspace observed: (i) students' learning is more active, (ii) more interaction between students and professors, through different areas (iii) at an early stage, students get in contact with the professional reality of their field, as the projects are related to real Engineering problems, and (iv) students develop transversal skills.
Practical implications: This paper identifies the potential that Makerspaces offer as a strategic approach to teaching and learning related to the fourth industrial era. This paper implies that universities and academics that wish to tailor their education to industry 4.0 need understand this model better, and where appropriate invest in educational infrastructures such as this in universities, companies or cities. This will ensure that universities are educating professionals with the most suitable skills for industry and society, generating innovation in creative teaching and learning spaces.
Research Limitations: The study is limited to one empirical research, analysis, and observation of a case study that can serve as a basis for future studies in other locations.
Design science in operations management: conceptual foundations and literature analysis
Authors: Dresch Aline , Pacheco Lacerda Daniel , Cauchick-Miguel Paulo Augusto 
Published: June 2019

Goal: The aim of this paper is to show that design science and design science research may contribute as a methodological approach in the context of operations management.
Design/methodology/approach: A systematic literature review was conducted to identify articles that have applied design science and design science research in operations management studies.
Results: The findings show that the concepts of design science and design science research are relevant and can be applied to conduct more relevant research. Moreover, this paper presents appropriate steps for conducting design science research and provides a summary of the main studies conducted in operations management until the present time. Some drivers are also suggested for advancing research in design science and design science research in operations management.
Limitations of the investigation: The main limitation of this paper is the lack of an empirical approach.
Practical implication: This paper can contribute to other researchers in the sense of presenting a methodological approach that can help reducing the gap that exists between the research that is developed by academics and what is necessary to support practitioners in organizations, mainly in operations management problems.
Originality/value: Publications that discuss research in the area of operations management generally consider the aims and practices determined by traditional sciences (natural and social) as a reference. Thus, it is important to explain the core concepts and foundations, as well as presenting the papers, which have already been developed using design science research in operations management, is necessary for advancing the discussion regarding the use of this method in this area.