bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib
Authors: Stein Eytan M. , DiNardo Courtney D. , Fathi Amir T. , Pollyea Daniel A. , Stone Richard M. , Altman Jessica K. , Roboz Gail J. , Patel Manish R. , Collins Robert , Flinn Ian W. , Sekeres Mikkael A. , Stein Anthony S. , Kantarjian Hagop M. , Levine Ross L. , Vyas Paresh , MacBeth Kyle J. , Tosolini Alessandra , VanOostendorp Jason , Xu Qiang , Gupta Ira , Lila Thomas , Risueno Alberto , Yen Katharine E. , Wu Bin , Attar Eyal C. , Tallman Martin S. , de Botton Stéphane 
Published: December 2018

Abstract
Approximately 8% to 19% of patients with acute myeloid leukemia (AML) have isocitrate dehydrogenase-2 (IDH2) mutations, which occur at active site arginine residues R140 and R172. IDH2 mutations produce an oncometabolite, 2-hydroxyglutarate (2-HG), which leads to DNA and histone hypermethylation and impaired hematopoietic differentiation. Enasidenib is an oral inhibitor of mutant-IDH2 proteins. This first-in-human phase 1/2 study evaluated enasidenib doses of 50 to 650 mg/d, administered in continuous 28-day cycles, in patients with mutant-IDH2 hematologic malignancies. Overall, 214 of 345 patients (62%) with relapsed or refractory (R/R) AML received enasidenib, 100 mg/d. Median age was 68 years. Forty-two patients (19.6%) attained complete remission (CR), 19 patients (10.3%) proceeded to an allogeneic bone marrow transplant, and the overall response rate was 38.8% (95% confidence interval [CI], 32.2-45.7). Median overall survival was 8.8 months (95% CI, 7.7-9.6). Response and survival were comparable among patients with IDH2-R140 or IDH2-R172 mutations. Response rates were similar among patients who, at study entry, were in relapse (37.7%) or were refractory to intensive (37.5%) or nonintensive (43.2%) therapies. Sixty-six (43.1%) red blood cell transfusion–dependent and 53 (40.2%) platelet transfusion–dependent patients achieved transfusion independence. The magnitude of 2-HG reduction on study was associated with CR in IDH2-R172 patients. Clearance of mutant-IDH2 clones was also associated with achievement of CR. Among all 345 patients, the most common grade 3 or 4 treatment-related adverse events were hyperbilirubinemia (10%), thrombocytopenia (7%), and IDH differentiation syndrome (6%). Enasidenib was well tolerated and induced molecular remissions and hematologic responses in patients with AML for whom prior treatments had failed. The study is registered at www.clinicaltrials.gov as #NCT01915498.
FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL
Authors: Close Viola , Close William , Kugler Sabrina Julia , Reichenzeller Michaela , Yosifov Deyan Yordanov , Bloehdorn Johannes , Pan Leiling , Tausch Eugen , Westhoff Mike-Andrew , Döhner Hartmut , Stilgenbauer Stephan , Oswald Franz , Mertens Daniel 
Published: December 2018

Abstract
NOTCH1 is mutated in 10% of chronic lymphocytic leukemia (CLL) patients and is associated with poor outcome. However, NOTCH1 activation is identified in approximately one-half of CLL cases even in the absence of NOTCH1 mutations. Hence, there appear to be additional factors responsible for the impairment of NOTCH1 degradation. E3-ubiquitin ligase F-box and WD40 repeat domain containing-7 (FBXW7), a negative regulator of NOTCH1, is mutated in 2% to 6% of CLL patients. The functional consequences of these mutations in CLL are unknown. We found heterozygous FBXW7 mutations in 36 of 905 (4%) untreated CLL patients. The majority were missense mutations (78%) that mostly affected the WD40 substrate binding domain; 10% of mutations occurred in the first exon of the α-isoform. To identify target proteins of FBXW7 in CLL, we truncated the WD40 domain in CLL cell line HG-3 via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9). Homozygous truncation of FBXW7 resulted in an increase of activated NOTCH1 intracellular domain (NICD) and c-MYC protein levels as well as elevated hypoxia-inducible factor 1-α activity. In silico modeling predicted that novel mutations G423V and W425C in the FBXW7-WD40 domain change the binding of protein substrates. This differential binding was confirmed via coimmunoprecipitation of overexpressed FBXW7 and NOTCH1. In primary CLL cells harboring FBXW7 mutations, activated NICD levels were increased and remained stable upon translation inhibition. FBXW7 mutations coincided with an increase in NOTCH1 target gene expression and explain a proportion of patients characterized by dysregulated NOTCH1 signaling.
Psychosexual history-taking in the 21st century: new terminology, new technology and new risks
Authors: Gardiner Lisa 
Published: December 2018

SUMMARYSexual and relationships difficulties are not uncommon among psychiatric patients. A presenting complaint of anxiety or depression may relate to an underlying sexual or relationship difficulty; commonly used psychotropic medications cause sexual side-effects that can have a significant impact quality of life, relationship maintenance and treatment adherence; patients may exhibit unusual or excessive sexual behaviours when acutely unwell, including risky use of apps to meet sexual partners and accessing online pornography in unsafe ways; patients may have used technology such as the internet to harm others or they may be victims of such harm; the internet and social media might even be influencing sexual expression, for example gender identity. Therefore, psychosexual history-taking remains a key competency for psychiatrists. They must also understand the new language used to describe sexuality, sexual behaviours and the use of social media, apps and so on to form relationships. This article outlines the key areas to consider in carrying out a structured psychosexual assessment. It also gives an overview of current sexual terminology, observed influences of the internet on sexuality and sexual behaviour, and its implications for mental health and potential sexual offending.LEARNING OBJECTIVESAfter reading this article you will be able to:
•outline a framework for psychosexual history-taking•recognise emerging terminology relating to sexual behaviours and identity•understand the relevance of the internet, social media and technology-based apps to human relationships, including the use of technology in sexual offendingDECLARATION OF INTERESTNone.
Developing an Indonesian fertility preservation questionnaire for health care providers treating patients with cancer: A preliminary pilot study
Authors: Harzif Achmad Kemal , Surya Raymond , Maidarti Mila , Mariana Ana , Lovita Bara Tracy , Wiweko Budi 
Published: December 2018

Background: Early detection and advanced treatment increases the five-year survival rate of patients with cancer. However, long-term cancer therapy, such as chemotherapy and radiotherapy, can have negative effects, such as infertility. This study aimed to develop a standardized Indonesian questionnaire, which would be used to assess the quality of health care providers’ knowledge, attitude, and practice regarding fertility preservation in patients with cancer. Methods: A pilot study was performed in January and February 2018 at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. An existing questionnaire was translated from English to Indonesian using forward translation, back translation, expert panel, pretesting, and cognitive interviewing. Ten subspecialists in the following departments made up an expert panel, who were involved in pretesting and cognitive interviewing: pediatric hematology-oncology, hematology-oncology/internal medicine, gynecologic oncology, gynecologic immune-endocrinology, radiology-oncology, and surgical oncology. Results: The questionnaire was successfully translated. The ten respondents stated that the maximum age for women’s fertility preservation is 40 years of age (60%), 45 years of age (30%), or had no maximum age (10%). Additionally, the respondents stated that the maximum age for men’s fertility preservation is 40 years of age (30%), 50 years of age (20%), or had no maximum age (50%). The respondents’ knowledge stated that > 50% of them were aware but do not know enough about fertility preservation. The respondents stated that more than 50% of them give feedback agreeing to fertility preservation, and they always give advice about fertility preservation to their patients. Conclusion: The translation of the questionnaire followed translation steps from the World Health Organization and was adjusted based on the expert panel’s comments concerning fertility preservation. This validated questionnaire tool in Indonesian can be used for research purposes and clinical evaluation of fertility preservation among health care providers in Indonesia.
Creative practice with clay: A mutual route to recovery?
Authors: Argyle Elaine , Winship Gary 
Published: December 2018

Abstract
This article summarizes the findings of a project called ‘Clay Transformations’ and was part of the Creative Practice as Mutual Recovery Programme funded by the Arts and Humanities Research Council. Using a mixed methods approach, the project aimed to assess the extent to which involvement in clay workshops promoted the well-being of a group of 42 participants, including mental health service users, artists and practitioners. A particular focus in this respect was placed on the incidence of ‘mutual recovery’ which extends the concept of recovery beyond the individual to incorporate the wider group and its context. It was subsequently found that workshop involvement helped to promote, not only the well-being and mutual recovery of participants, it also enhanced the supportive capacities and social capital of the settings in which these activities took place, both within the workshops and beyond.
Reviews
Authors: Zhang Shuai , Xu Xiaoyan , Bicer Elcin , Herbert Carrie , Demaine Krystal , Morrison Amy 
Published: December 2018

Abstract
Digital Bodies: Creativity and Technology in the Arts and Humanities, Susan Broadhurst And Sara Price (eds) (2017) London: Palgrave Macmillan, 270 pp., ISBN: 978-1-34995-240-3, h/bk, $99.99
Acting, Spectating and the Unconscious: The Psychoanalytic Perspective on Unconscious Processes of Identification in the Theatre, Maria Turri (2016) New York: Routledge, 132 pp., ISBN: 978-1-31551-733-9, eBook, $28.98
Nourish: Cambodia’s 1st Creative Arts Therapy and Wellbeing Conference, Phnom Penh, 16–18 January 2018
The Indigenous Roots of Expressive Arts Therapy: Report on the 12th Biannual International Expressive Arts Therapy (IEATA ) Conference, Winnipeg, 4–8 OCTOBER 2017
La construcción de conocimiento y la integralidad de funciones en la agenda actual de la extensión universitaria
Authors: Zabaleta Verónica 
Published: December 2018

El presente trabajo se propone abordar la temática de la construcción de conocimiento en relación con las prácticas extensionistas y vincular la relevancia de este tema con dos cuestiones principales. Por un lado, con la necesidad de revalorizar saberes no académicos si la universidad pretende establecer un diálogo con la comunidad a la que pertenece. Por otro lado, con el carácter estructurante del conocimiento no solo para la extensión sino también para el resto de las funciones sustantivas de la universidad. De aquí se deriva el análisis de la integralidad como tema de la agenda de la extensión universitaria y de lo que se ha denominado la “Segunda Reforma Universitaria”. El problema epistemológico que el trabajo aborda se articula, asimismo, con cuestiones de índole ética y política
Extensión universitaria y cooperativas: prácticas y perspectivas de una década (Argentina, 1958–1968)
Authors: Vuotto Mirta 
Published: December 2018

La extensión universitaria ha sido objeto de algunas consideraciones acerca de su naturaleza y el papel que debe ocupar entre las principales funciones institucionales. Sin embargo, pocos trabajos han planteado una reflexión sobre su impacto a la luz de las realizaciones ocurridas en el campo específico de las cooperativas.
El artículo se propone definir y analizar los principales rasgos de un programa de extensión impulsado por la Universidad de Buenos Aires entre 1958–1968 para propiciar espacios de promoción del apoyo y asistencia de la actividad de las cooperativas. Se introducen antecedentes sobre el origen de la extensión universitaria para caracterizar el programa y mencionar la contribución al mismo por parte de la Facultad de Ciencias Económicas.
Como conclusión, se plantea una reflexión sobre las modalidades de los programas de extensión para desarrollar estrategias efectivas que permitan mejorar el compromiso de las universidades en una perspectiva de largo plazo.
Computational simulation applied in choosing the best solution in a product development using design for manufacturing and assembly approach
Authors: Pinheiro Nathália Marcia Goulart , Ordoñez Robert Eduardo Cooper , Barbosa Gustavo Lemes Leite , Dedini Franco Giuseppe 
Published: December 2018

Highlights: The product development methodology aims to assist the planning and design of the product throughout its life cycle. Using selection criteria it is possible to choose a solution will be followed until the end of the development process and this process is known as optimization of product solutions. Design for Manufacturing and Assembly (DFMA) is an approach that allows selecting a product solution with better manufacturing and assembly performance. Computational modeling allows representing systems in virtual environment in order to reproduce its characteristics and to compare scenarios through simulation.
Goal: The objective of this work was to apply the computer simulation to compare the productive performance, according to production times, productivity and resource utilization rate, of three solutions proposed for a raincoat for pets with thermal protection.
Methodology: Initially, conceptual models representing the production systems for the three product solutions were generated. The systems were modeled in discrete event simulation software, enabling different scenarios testing, resulting in production performance indicators for each product solution.
Results: The analysis of the performance indicators allow identifying that the third solution proposed for the product obtained the best productive performance in all proposed scenarios; therefore, it was chosen as the best solution for the product according to the DFMA approach.
Limitations of the investigation: The application of the methodology indicated in this work was limited to the study of a single productive system of a specific product.
Practical implications: This work presents a practical application of computer simulation tools applied to product development.
Originality / Value: The original contribution of this work is the application of computational simulation of production systems in product development following the DFMA approach.
Distribution of Heavy Metals (Ni, Co, Pb, Cd, Hg) in Tissues of European Chub (Squalius cephalus L.) from the Middle Course of the Nitra River, Slovakia
Authors: Andreji Jaroslav , Dvořák Petr , Fik Martin 
Published: December 2018

Abstract
The aim of this study was to determine the levels of Ni, Co, Pb, Cd and Hg in the muscle, hepatopankreas, kidney and gonads of European chub (Squalius cephalus) from the middle course of the Nitra River, during spring and autumn seasons by AAS method. The concentrations of metals (mg.kg-1 wet weight) in the muscle ranged as follows: Ni 0.15-1.18, Co 0.09-0.58, Pb 0.39-1.66, Cd 0.04-0.29, Hg 0.85-2.71. Statistically significant differences among individual tissues, as well as between seasons have been recorded. Higher metals concentrations were detected in inner organs than in muscle. Permissible limits for safe consumption in the case of Pb, Cd and Hg have been exceeded in 100%, 95% and 100%, respectively. Currently, for the Co and Ni are not set any permissible limits.
Automatic control of grasping strength for functional electrical stimulation in forearm movements via electrode arrays
Authors: Salchow-Hömmen Christina , Thomas Till , Valtin Markus , Schauer Thomas 
Published: December 2018

Abstract
The generation of precise hand movements with functional electrical stimulation (FES) via surface electrodes on the forearm faces several challenges. Besides the biomechanical complexity and the required selectivity, the rotation of the forearm during reach-and-grasp tasks leads to a relative change between the skin and underlying tissue, resulting in a varying FES response. We present a new method for automatic adaptation of virtual electrodes (size, position) and stimulation intensity in an electrode array to guarantee a secure grasp during forearm movements. The method involves motion tracking of arm and hand with inertial sensors. This enables the estimation of grasping strength when using elastic objects. Experiments in healthy volunteers revealed that our method allows generating a strong, stable grasp force regardless of the rotational state of the forearm.
Optimizing controlled laser cutting of hard tissue (bone)
Authors: Beltran Bernal Lina M. , Schmidt Iris T. , Vulin Nikola , Widmer Jonas , Snedeker Jess G. , Cattin Philippe C. , Zam Azhar , Rauter Georg 
Published: December 2018

Abstract
Conventional bone surgery leads to unwanted damage to the surrounding tissues and a slow healing process for the patients. Additionally, physicians are not able to perform free cutting shapes due to the limitations of available systems. These issues can be overcome by robot-assisted contactless laser surgery since it provides less mechanical stress, allows precise functional cuts, and leads to faster healing. The remaining drawback of laser surgery is the low ablation rate that is not yet competitive with conventional mechanical piezo-osteotomes. Therefore, we aim at maximizing the efficiency in hard tissue laser ablation by optimizing the lateral movement speed for different irrigation conditions.
The results of this study show a non-linear relationship between cutting rates, speeds, and depths that should be critically considered for integration in robotic laser surgery.
Teaching the pony new tricks: competences for specialists in laboratory medicine to meet the challenges of disruptive innovation
Authors: Wieringa Gijsbert 
Published: December 2018

Abstract
The 20th century digital revolution has already seen the introduction of faster, more diverse, easier to use technologies with extended capacity and capability that has enhanced productivity in Laboratory Medicine and allowed more effective use of human resource. With increasing demands for better health and best care the challenge to future healthcare systems is to deploy technology, facilities and human resources more effectively. For the 21st century the digital age heralds opportunities for information-led technology providers to become healthcare providers when algorithm driven care can support patients’ needs at the point of care close to or in their homes. For Specialists in Laboratory Medicine the opportunity arises for working beyond the laboratory in partnership with the emerging providers. The challenge to specialists is to extend their skill and competence to leadership roles that (a) determine clinical need and strategic direction for local environments, (b) ensure technology solutions are cost-effective, safe and reliable, (c) assume the business acumen to market, negotiate and manage change in services, (d) expect understanding of the clinical bioinformatics that underpin genomics, health information science (data mining and health economics) and physical sciences (e) expect knowledge and skills in the provision of direct clinical care in the face of staffing shortfalls experienced by many healthcare systems and (f) enhance their communication and interactive skills. In growing their leadership contribution a partnership approach in education and training across healthcare divides, in conjunction with the diagnostics and/or information technology industries, through integrated professional organisation approaches, joint approaches with academia and policy related healthcare organisations is recommended.
Blood contamination in salivary diagnostics: current methods and their limitations
Authors: Kang Jeong-Hyun , Kho Hong-Seop 
Published: December 2018

Abstract
The use of saliva samples in clinical studies has increased. However, the diagnostic value of whole saliva is compromised in the presence of blood contamination, owing to the higher levels of analytes in blood compared with those in saliva. The aim of this study was to review the existing methods and their limitations for measuring the levels of blood contamination in saliva. A literature search was performed using Web of Science, SCOPUS, and PubMed databases and 49 articles dealing with salivary diagnostics and measurements of blood contamination were included. Five methods for measuring the degree of blood components in saliva were discussed, including “visual inspection”, use of “strip for urinalysis”, and detection of plasma proteins such as “hemoglobin”, “albumin”, and “transferrin”. Each method has its limitations, and transferrin has been regarded as the most reliable and valid marker for blood contamination in saliva. However, transferrin in whole saliva may not be solely a product of blood, and its level in whole saliva can be influenced by several factors such as age, gonadal hormones, salivary flow rate, chewing performance, and oral microorganisms. In conclusion, when quantitatively analyzing whole saliva samples, the influence of blood contamination should be considered.
Analysis and evaluation of the external quality assessment results of quality indicators in laboratory medicine all over China from 2015 to 2018
Authors: Duan Min , Kang Fengfeng , Zhao Haijian , Wang Wei , Du Yuxuan , He Falin , Zhong Kun , Yuan Shuai , Chen Bingquan , Wang Zhiguo 
Published: December 2018

Abstract

Background
This study aimed to comprehensively evaluate laboratory quality in China and explore factors affecting laboratory errors through analyzing the external quality assessment (EQA) results of quality indicators (QIs).

Methods
According to model 3 (interpretive) of the proficiency testing scheme, the National Center for Clinical Laboratories of China (CNCCL) developed a questionnaire for 15 QIs. Clinical laboratories from different provinces of China participated in the EQA program of QIs annually and submitted data via an online reporting system named Clinet-EQA. The results of QIs were expressed in percentage and sigma value or minute. Three levels of quality specifications (QSs) were defined based on percentile values. Furthermore, the QIs were analyzed by disciplines, hospital scales and information construction levels of participant laboratories.

Results
A total of 3450 laboratories nationwide continuously attended the EQA program and submitted complete data from 2015 to 2018. The performance of most QIs has improved year by year. QIs in post-analytical gained the best performance with sigma values that varied from 5.3σ to 6.0σ. The comparison of results among different disciplines showed significant differences for five QIs. More than half of QIs had statistical differences among different hospital scales measured by hospital grades and number of hospital beds. The performance of nine QIs were influenced by information construction levels of participant laboratories.

Conclusions
The overall laboratory quality in China has improved since the initiation of EQA program for QIs, but the performance of some QIs was still unsatisfactory. Therefore, laboratories should make efforts for continuous quality improvement based on information provided by QSs.