bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating monocytes and tumor‐associated macrophages express recombined immunoglobulins in glioblastoma patients
Authors: Busch Svenja , Talamini Marina , Brenner Steffen , Abdulazim Amr , Hänggi Daniel , Neumaier Michael , Seiz‐Rosenhagen Marcel , Fuchs Tina 
Published: June 2019

AbstractBackgroundGlioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor‐associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCRαβ in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor‐associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets.ResultsWe routinely find consistent expression of immunoglobulins in tumor‐associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V‐chain usage, CDR3‐length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences.ConclusionsThe investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma‐patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients’ B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor‐specific immune response which could be advantageous for the use as diagnostic or therapeutic target.
Evolutionary biology: an essential basic science for the training of the next generation of psychiatrists
Authors: Abed Riadh , Ayton Agnes , St John-Smith Paul , Swanepoel Annie , Tracy Derek K. 
Published: June 2019

SummaryEvolutionary science can serve as the high-level organising principle for understanding psychiatry. Evolutionary concepts generate new models and ideas for future psychiatric study, research, policy and therapy. The authors accordingly make the case for the inclusion of evolutionary biology in the postgraduate education of psychiatric trainees.
Transition between child and adult services for young people with attention-deficit hyperactivity disorder (ADHD): findings from a British national surveillance study
Authors: Eke Helen , Ford Tamsin , Newlove-Delgado Tamsin , Price Anna , Young Susan , Ani Cornelius , Sayal Kapil , Lynn Richard M. , Paul Moli , Janssens Astrid 
Published: June 2019

BackgroundOptimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.AimsTo estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.MethodSurveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.ResultsQuestionnaire response was 79% at baseline and 82% at follow-up. For those aged 17–19, incident rate (range adjusted for non-response) of transition need was 202–511 per 100 000 people aged 17–19 per year, with successful transition of 38–96 per 100 000 people aged 17–19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.ConclusionsAs inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.
Disturbances in Insulin–Glucose Metabolism in Patients With Advanced Renal Disease With and Without Diabetes
Authors: Rahhal Marie-Noel , Gharaibeh Naser Eddin , Rahimi Leili , Ismail-Beigi Faramarz 
Published: June 2019

AbstractContextUse of insulin in patients with diabetes and advanced chronic kidney disease (CKD; stages 4 to 5) is challenging and shows great variability among individuals. We explored the mechanisms underlying this variability.Evidence AcquisitionPubMed was searched for articles in English from 1960 to 2018 for advanced CKD and diabetes, glucose and insulin metabolism, insulin clearance, secretion and resistance, plasma insulin concentration, glycemic control, hypoglycemia, insulin dosage, and continuous glucose monitoring (CGM) in CKD.Evidence SynthesisThe evidence shows that in most patients the daily dose of insulin needs to be significantly reduced with a high degree of variability; in some the dose remains unchanged, and rarely it is increased. The premise that the marked reduction in insulin requirement is essentially attributable to decreased insulin clearance by kidneys leading to prolongation of its plasma half-life, elevated blood insulin concentration, and hypoglycemia is not entirely correct. Other factors including decreases in food intake, insulin secretion, insulin clearance by peripheral tissues, and renal gluconeogenesis play important roles. There is also heightened resistance to insulin due to metabolic acidosis, uremic toxins, inflammatory state, and vitamin D deficiency. Importantly, the magnitude of changes in each of these factors varies between individuals with the same degree of CKD.ConclusionsIn the presence of diabetes with advanced CKD, the insulin regimen should be individualized based on knowledge of the daily glucose patterns. The use of CGM is promising for safer glycemic control in patients with advanced CKD and diabetes and helps prevent extremes of hypoglycemia and hyperglycemia.
Total Syntheses of the Non-Peptide Bradykinin B1 Receptor Antagonist Velutinol A and Its Analogs,seco-Pregnanes with a Cage-Like Moiety
Authors: Tamiya Minoru , Isaka Nobuhisa , Kitazawa Takaaki , Hasegawa Atsushi , Ishizawa Kazuya , Ikeda Mayu , Kawada Saki , Ishiguro Masaji 
Published: June 2019

AbstractWe describe here the syntheses of velutinol A (1) and the structurally similar compounds 2–4 sharing a highly oxygenated seco-pregnane cage-like structure. The synthesis of velutinol A (1, 15,16-seco-pregnane) features the highly regioselective construction of Δ14 silyl enol ether from 15-keto-21,22-diol, followed by stereoselective introduction of a sterically hindered β-hydroxy group at the C14 position by Rubottom oxidation. Prolonged reaction time and the use of an excess amount of mCPBA at this step allowed double Rubottom oxidation, enabling us to introduce the requisite hydroxy groups at the C14 and C16 positions in one pot. Subsequent oxidative cleavage of the C15–16 bond, deprotection, and intramolecular acetalization allowed the concise total synthesis of velutinol A (1). Utilization of α,α-dihydroxyketone, the double Rubottom oxidation product, for formation of the ether F-ring by 5-exo-cyclization, and subsequent C14–21 oxidative cleavage, effectively achieved the synthesis of pentalinonside-aglycon (2). Construction of the 14,15-seco-structures of two other analogs, argeloside aglycon (3) and illustrol (4), was achieved by Baeyer–Villiger oxidation of 15(21)-keto derivatives. Introduction of the 20-oxo group potentially embedded in argeloside aglycon was accomplished by Wacker oxidation of Δ20, which was constructed by Grieco–Nishizawa syn-β-elimination of the C21-primary alcohol obtained by reduction of the Baeyer–Villiger product. Intramolecular double acetalization of the 15,16-dihydroxy-14,20-oxo derivative to form the cage-like structure of the DEF-rings required a moderately weak acid. This step was the key to accessing argeloside aglycon (3), as otherwise the easily aromatized β,γ-dihydroxyketone moiety was transformed to furan. Sharpless asymmetric dihydroxylation of Δ20 to set the C20 stereocenter, followed by intramolecular double acetalization, achieved the stereoselective synthesis of illustrol With all synthesized compounds, structural requirements of steroidal bradykinine B1 receptor antagonist would be revealed.
African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa
Authors: Dandara Collet , Masimirembwa Collen , Haffani Yosr Z. , Ogutu Bernhards , Mabuka Jenniffer , Aklillu Eleni , Bolaji Oluseye ,   H3Africa
Published: June 2019

The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent. Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition. Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.
The Value of Commitments When Selling to Strategic Consumers: A Supply Chain Perspective
Authors: Kabul Mustafa O. , Parlaktürk Ali K. 
Published: June 2019

We consider a decentralized supply chain consisting of a retailer and a supplier that serves forward-looking consumers in two periods. In each period, the supplier and the retailer dynamically set the wholesale and retail price to maximize their own profits. The consumers are heterogeneous in their evaluations of the product and are strategic in deciding whether and when to buy the product, choosing the option that maximizes their utility, including waiting for a price markdown. We derive the equilibrium and study the value of price and quantity commitments from both the retailer’s and the supplier’s perspectives. We find that, although a centralized system always benefits from making price and quantity commitments, this is not true for a firm in a decentralized supply chain due to how the other firm responds to these commitments. We show that the retailer suffers from making a price or quantity commitment and that, similarly, the supplier does not benefit from making a price commitment. In these cases, commitments can harm not only the firm itself but also profitability of the other firm in the supply chain, thereby disadvantaging the entire supply chain. This happens because such commitments aggravate double-marginalization inefficiency in the supply chain. Furthermore, we show that eliminating this inefficiency through a coordinating contract (e.g., a two-part tariff or quantity discount) makes commitments beneficial. This paper was accepted by Martin Lariviere, operations management.
Hybrid project management for sociotechnical digital transformation context
Authors: Monteiro Cavalieri Barbosa Adriane , Pego Saisse Manoel Carlos 
Published: June 2019

Goal: The path to implement Digital Transformation (DT) in modern industries is far from clear, particularly in Brazil. From the point of view of operations management, authors developed a Conceptual Framework (CF) to support DT implementation in Discrete Manufacturing Industries (DMI). The CF applies knowledge management, hybrid project management (HPM) and Sociotechnical values to implement DT, using New Product Development (NPD) as a ground. The work aims to depict the HPM approach of this CF.
Design / Methodology / Approach: this is a qualitative research based on a systematic literature review carried out over a period of five years. It was performed in the Web of Science database, applying PRISMA flowchart, to evaluate which project management models, addressed in the literature, are more suitable for DT implementation projects in light of sociotechnical and innovation-shared-values approach.
Results: A Hybrid “Stage-Gate – Agile - Design Thinking” project management model to support DT implementation in DMI. This is a preliminary proposal that can be explored in future empirical research.
Limitations of the investigation: Some quality papers may have been left out due to the research methodology.
Practical implications: The CF can be applied by professionals to support Digital Transformation while incorporating sociotechnical values and reducing the excessive technological bias in NPD projects.
Originality/Value: The authors propose a new Digital Transformation (DT) approach, named Sociotechnical Digital Transformation (SDT) and an HPM to support DT in light of a Sociotechnical approach.
Using multicriteria analysis and fuzzy logic for project portfolio management
Authors: Agápito Andrezza De Oliveira , Vianna Marcilene De Fátima Dianin , Moratori Patrick B. , Vianna Dalessandro Soares , Meza Edwin Benito Mitacc , Matias Italo De Oliveira 
Published: June 2019

Goal: to propose a hybrid method, combining AHP and Fuzzy, for project portfolio management.
Originality/value: this paper meets the positive characteristics of both methods, adequately weighing the criteria and contemplating process subjectivity. Limitations that exist in both methods, such as the maximum number of alternatives and the difficulty of inserting new alternatives at the end of the process, are overcome.
Design/methodology/approach: the AHP is applied for determining the criteria weights and fuzzy is used to compare the alternatives for each criterion.
Results: the results show that the proposed hybrid method allows the ranking of many alternatives and provides higher reliability for decision makers. It must be noted that the system is fed by performance indicators, which minimize the subjectivity in decision-making—an important characteristic in the technology management. Moreover, the results provide the possibility of changing the number of projects at any time without influencing the outcome.
Practical implications: the proposed hybrid method can be used in different problems that have many alternatives or subjectivity.
Understanding Industry 4.0: Definitions and insights from a cognitive map analysis
Authors: Benitez Guilherme Brittes , Ferreira Lima Mateus José do Rêgo , Lerman Laura Visintainer , Frank Alejandro Germán 
Published: June 2019

Goal: The purpose of this paper is to present an analysis of Industry 4.0 concepts and technologies through the lens of practitioners and scholars with considerable expertise in this field.
Design / Methodology / Approach: A qualitative research was conducted based on seven semi-structured interviews guided by an open questionnaire, which was developed with the main goal of understanding the concept of Industry 4.0 and the technologies that compose this industrial phenomenon.
Results: Based on this methodology, a cognitive map is presented as the result and final product of this study. This cognitive map is composed of five different clusters, each one represented by different colors, which relate to each of the questions in the questionnaire. Our analysis provides a better understanding of (i) the main concepts of Industry 4.0; (ii) the implementation stages for companies; (iii) the main enabling technologies; (iv) the concept of M2M (machine-to-machine); and (v) the scenario in Brazil. Each one of the clusters enables a discussion by bringing what is in the literature on the topic.
Limitations of the investigation: The main limitations of the article are found in the subjectivity of the results and also in the scarcity in the literature related to some topics covered in the clusters.
Practical implications: This research can be potentially useful for practitioners, since it sheds light on the Industry 4.0 concept and how technologies are used to integrate processes.
Originality / Value: The clusters answers of the cognitive map allowed comparisons with the literature and a discussion about Industry 4.0, making it possible to direct and check gaps in the research.
Innovation capability maturity in non-R&D performers: a reference model
Authors: Baptista Narcizo Ramon , Gabbay Canen Alberto , Tammela Iara , Cardoso Rodolfo , Eleutério Delesposte Jamile 
Published: June 2019

Highlights: The prevalence of Research and Development (R&D) as an inducing factor for innovation has been questioned, and studies show that low-tech companies are able to innovate. Innovation capability is essential to increase productivity and improve competitiveness. However, when formal R&D is considered as the main parameter in its evaluation, it tends to underestimate it. The extent and heterogeneity of studies on innovation in non-R&D practitioners is a relevant problem and, despite theoretical and empirical advances, it is not satisfactorily resolved yet.
Goal: This article presents a reference model for innovation capability maturity in low-technology, non-R&D performing companies, oriented to guide decision makers and the institutions supporting these organizations.
Design / Methodology / Approach: The method used to construct the model is based on the proposition of Ahlemann and Gastl (2007) for the construction of reference models based on empirical evidence.
Results: The model is based on ten organizational dimensions and their effects on the organization's performance. Five maturity levels are defined, synthesizing the fundamental characteristics of innovation capability in non-R&D practitioners or low technology companies.
Limitations of the investigation: Although the model has been tested and validated, more applications and tests may still be required.
Practical implications: The model is an important tool for decision-making, at the management level, in low-tech companies that aspire to broaden their innovation capability.
Originality / Value: The model has significant potential academic repercussions, in terms of the expansion of knowledge, as well as for the industry, since it can contribute to the increase of the competitive performance of companies.
Design principles for research & development performance measurement systems: a systematic literature review
Authors: Oliveira Andre Ribeiro de , Proença Adriano 
Published: June 2019

Goal: This paper aims to set the foundation on which a performance measurement system for the R&D function will be developed, assuming it not only as an organizational division, but also as a comprehensive process in order to better evaluate its efficiency and effectiveness.
Design/Methodology/Approach: This paper adopts a Design Science Research strategy as its methodological basis. It focuses on bringing guidelines from the body of organizational theory of knowledge to design effective management solutions for an R&D performance measurement system.
Results: A set of well-defined Design Principles to guide performance measurement system designs for R&D management.
Limitations of the investigation: Even though the design principles have been systematically obtained from the literature review, there was no adequacy test of these principles in practical cases, which should be conducted in future research.
Practical Implications: Managers and leaders of R&D teams may use theory-grounded guidelines to design their performance systems and to adjust such systems to their specific needs.
Originality/ Value: The main practical contribution of the study findings is to provide a comprehensive set of guidelines to design a R&D Performance Measurement System, rather than proposing another new complete theoretical framework to add to the literature.
A formação de professores-pesquisadores em Educação Especial durante a ditadura no Brasil
Authors: Souza Flávia Faissal de , Pletsch Márcia Denise , Batista Getsename de Freitas 
Published: June 2019

A institucionalização da Educação Especial ocorreu durante o regime da ditadura, com a criação do Centro Nacional de Educação Especial (Cenesp), mediante convênios internacionais para a formação de professores-pesquisadores na Educação Especial. O objetivo deste artigo é analisar a influência das diretrizes internacionais da ONU e dos Acordos MEC/Usaid na estruturação das propostas do Cenesp para formação de professores-pesquisadores da área. Para tal, realizamos uma pesquisa documental e uma entrevista semiestruturada com a primeira diretora-geral do Cenesp. Ao discutir o contexto internacional e nacional da época, nossa análise problematiza o lugar da pesquisa e da formação de professores para a Educação Especial.
Against the parallelism between the NP and the clause: Evidence from idioms
Authors: Cecchetto Carlo , Donati Caterina 
Published: June 2019

Abstract
We argue that the counterpart of Marantz’s generalization does not hold in the nominal domain, because there are idioms in which the determiner and the noun receive an idiomatic meaning while the PP that modifies the noun is not part of the idiom (we call these “PP-less idioms”). We show that PP-less idioms are fully expected if the hypothesis of parallelism between nominal structure and clausal structure is dropped and it is assumed that the first step of the derivation in the nominal domain involves merge of D and N.
As for the mirror image of PP-less idioms, “PP-containing idioms”, namely DPs where N and the PP that follows the noun receive an idiomatic reading while D does not, we suggest that they are not generated by syntax but are rather the output of the morphological component.
A study on numerical integration methods for rendering atmospheric scattering phenomenon
Authors: Gałaj Tomasz , Wojciechowski Adam 
Published: June 2019

Abstract
A qualitative comparison of three, popular and most widely known numerical integration methods in terms of atmospheric single scattering calculations is presented. A comparison of Midpoint, Trapezoidal and Simpson’s Rules taking into account quality of a clear sky generated images is performed. Methods that compute the atmospheric scattering integrals use Trapezoidal Rule. Authors try to determine which numerical integration method is the best for determining the colors of the sky and check if Trapezoidal Rule is in fact the best choice. The research does not only conduct experiments with Bruneton’s framework but also checks which of the selected numerical integration methods is the most appropriate and gives the lowest error in terms of atmospheric scattering phenomenon.