bluuebunny/crossref_metadata_2025 huggingface dataset:
Le lien « alcool et grossesse » dans les formations en soins infirmiers et travail social, une thématique à reconsidérer ?
Authors: Hontebeyrie Juliette
Published: October 2018

La consommation d’alcool par les femmes enceintes et les dangers y afférents préoccupent de façon notable les pouvoirs publics depuis près de vingt ans. C’est à peine moins que l’âge qu’ont les actuels étudiants en fin de cursus de soins infirmiers ou de travail social. Or, les métiers qu’ils visent : infirmier diplômé d’État, assistant de service social, conseiller en économie sociale familiale ou éducateur spécialisé, peuvent les conduire, dans un avenir proche, à être au contact avec des femmes enceintes et consommatrices d’alcool. À partir d’une enquête menée dans un pôle de formation regroupant ces deux parcours d’enseignement, l’enquête vise à appréhender les connaissances et représentations des étudiants quant à leur future pratique de terrain relative à la question « alcool et grossesse ». Peu, voire pas formés sur cette thématique, les étudiants observés connaissent les dangers de la consommation d’alcool pendant la grossesse. Peu outillés en tant que futurs professionnels, ils se sentent cependant en relative capacité pour aborder cette question. Par ailleurs, une partie d’entre eux projette des représentations sociales erronées des publics qui seraient affectés par la consommation d’alcool au cours de la grossesse. Autant d’éléments qui interrogent les modalités des formations susceptibles de leur être dispensées.
Charlotte Tassé (1893-1974), infatigable promotrice du modèle de la garde-malade canadienne-française
Authors: Klein Alexandre
Published: October 2018

Personnage oublié de l’histoire des soins de santé comme de celle du Québec, Charlotte Tassé (1893-1974) fut pourtant une figure de proue de la professionnalisation des infirmières québécoises. Cette garde-malade canadienne-française a en effet créé et administré deux écoles d’infirmières, lancé et dirigé pendant trente-cinq ans une revue professionnelle de référence, participé activement à l’émergence du nursing psychiatrique dans sa province, possédé et administré l’un des principaux centres de soins de santé mentale du pays et même créé de toutes pièces une classe d’infirmières à part entière : les gardes-malades auxiliaires. Elle a surtout établi et défendu, avec ténacité et persévérance, à travers toutes ces réalisations, un modèle infirmier unique, propre au Québec : celui de la garde-malade canadienne-française. Entre valeurs traditionnelles du soin et de la féminité et représentations avant-gardistes du rôle des infirmières, qu’elle dédiait à la gestion des hôpitaux, elle a contribué avec ce modèle à faire de l’histoire québécoise des infirmières une histoire unique et originale. C’est sur la création de ce modèle infirmier inédit et sur la promotion active dont il a fait l’objet pendant près d’un demi-siècle que cet article 1 revient en retraçant, à partir d’archives inédites, le parcours hors-norme de Charlotte Tassé.
Les méthodes mixtes en systèmes d’information : enjeux épistémologiques et méthodologiques
Authors: Pascal Amandine , Aldebert Bénédicte , Rouziès Audrey
Published: October 2018

Les méthodes mixtes rencontrent un succès croissant dans les sciences sociales aujourd’hui, succès en partie lié à leur capacité à générer des résultats de recherche qui diffèrent de ceux obtenus par les méthodologies traditionnelles. À ce titre, les méthodes mixtes semblent fécondes pour le domaine des Systèmes d’Information (SI) notamment car elles offrent un large éventail de choix méthodologiques (Mingers, 2001 ; Venkatesh et al. , 2013). Cependant, nous disposons de peu de connaissance sur la façon dont les auteurs s’approprient justement ces méthodes et sur les choix qu’ils effectuent. Dans cette perspective, cet article a pour objet de mieux comprendre l’utilisation des méthodes mixtes faite par les chercheurs dans le domaine des SI afin d’appréhender s’il existe des tendances quant à l’usage de ce type de méthode et si ces méthodes sont rigoureusement mises en œuvre. Pour ce faire, à partir d’une revue de littérature comparative sur les méthodes mixtes en sciences sociales et en SI, une analyse bibliographique sur sept journaux en SI a été conduite sur la période 2008-2016. Cette analyse nous permet d’apporter un regard critique sur l’utilisation des méthodes mixtes en SI et de compléter ainsi les deux études bibliographiques réalisées par Mingers (2001) et Venkatesh et al. (2013). En ancrant sa réflexion dans l’épistémologie, cette analyse se distingue alors des précédentes ce qui en fait son originalité et sa force. Elle nous permet alors de proposer des recommandations pour les auteurs désireux de mettre en œuvre ce type de méthode.
Les périphrases en aller et venir de l’italien contemporain : grammaticalisation et effets de sens
Authors: Silletti Alida Maria
Published: October 2018

Cette contribution étudie les structures périphrastiques réalisées à partir des verbes de mouvement andare et venire en italien contemporain pour montrer leur complexité et leur richesse sémantico-syntaxique et pragmatique. Sur la base de travaux sur les périphrases verbales de l’italien (dont Bertinetto 1989-1990, 1996 et 1998 ; Squartini 1998 ; Bertinetto & Squartini 2016) et d’analyses ponctuelles sur leurs effets de sens, nous vérifions la fréquence et le fonctionnement de ces constructions au sein du corpus de référence de l’italien écrit contemporain CORIS / CODIS (sections : presse quotidienne et périodique ; corpus de suivi : « MONITORs ») et sur Internet. Des remarques intra- et interlinguistiques sur les périphrases des langues romanes contemporaines permettent d’identifier leurs points de contact et différences avec les structures de l’italien en vue de déceler les spécificités de cette langue.
Bridging the Gap Between Marketing Education and the Marketing Profession
Authors: Finch David J. , McIntyre Sharon
Published: October 2018

Professionals and scholars have discussed the unprecedented pace of change currently experienced by businesses. The dynamics facing business today offer rich insight into the challenges facing university graduates. In this chapter, the authors apply a dynamic capabilities (DCs) view of new graduate employability. Dynamic capabilities theory is rooted in the resource-based view that posits organizations create a competitive advantage by acquiring or developing resources that are rare, valuable, and hard to imitate and replace. They argue that employability can be viewed as the complex integration and application of four specific DCs: (1) intelligence resources, (2) personality resources, (3) meta-skill resources, and (4) job-specific resources. The authors view new graduate competitive advantage as dependent on the ability of university graduates to mobilize and exploit the linkages of these resources throughout their university study years. In adopting these resource categories, they build on previous work and propose a conceptual model to evaluate a new graduate's competitive position in an employment marketplace. In this chapter, the authors provide a prescription for how educators and students can apply an integrated dynamic capability view of new graduate employability to support the professional development of marketing students through the development of a comprehensive personal product roadmap.
Women in Organizations
Authors: Tan Basak Ucanok
Published: October 2018

There has been a retreat from the “conventional” work organization to new forms of contemporary organizations. Parallel to this shift in organizational forms, the composition of the workforce also changed. Greater numbers of women entered the labour market and began occupying managerial positions. Despite the increase of women in the workforce, progress towards equality lagged behind. The intention of this chapter is to provide an overall picture of the representation of women in organizations and to acquaint the readers with some of the major issues that play role in women's career advancement. The chapter begins by introducing macro and micro level barriers that hinder representation of women in the contemporary workplace. Some of these major barriers, such as stereotypes attached to women, occupational segregation, the gender pay gap, and discrimination are then detailed and theoretical and practical implications are provided. The chapter also covers studies on the leadership of women in organizations and outlines the need to unravel the potential of women.
The Performance Implications of Corporate Political Ties
Authors: Yılmaz Nazlı Berberoğlu
Published: October 2018

The main purpose of this chapter is to examine the performance implications of corporate political ties (CPT) that the business organizations establish with the government in the long run. Since the relevant literature mostly focuses on the outcome of these relations, they miss the process which creates the outcomes. Hence, there is no consensus over the performance implications of corporate political ties in the relevant literature. In the chapter, the author examines the CPT-performance relation by taking the process into the center of the study which is conducted in a state-dependent national business system. More specifically, the author examines how the Turkish organizations adapt their political ties in the face of changing political environment and what are the performance implications of this adaptation.
Democratic Citizenship Education in South Africa
Authors: Davids Nuraan
Published: October 2018

Underscoring the immense educational policy reform which accompanied the emergence of a democratic South Africa is an emphasis of the (re)alignment of rights, justice, and equitable access. It soon became apparent that, although educational reform aligned itself with notions of democratic citizenship education, inadequate attention was being given to, on the one hand, the capacity of teachers, and on the other hand, the willingness of teachers to assume responsibility for their roles as facilitators of citizenship education. The concern of this chapter is to consider the role of “the teacher” in relation to educational policy. Secondly, attention is given to the types of interventions availed to teachers in their roles as the facilitators of democratic citizenship education. The chapter concludes by showing that not only has educational policy reform been remiss of “the teacher,” but it is also this inattention that continues to undermine the democratic agenda within schools and beyond.
Higher Education and Citizenship in Latin America
Authors: Baisotti Pablo Alberto
Published: October 2018

In Latin America, public policies were promoted to encourage students to attend university and to create new institutions. However, the resources used for these purposes were scarce, as were those used to promote the integration of students from the most vulnerable social sectors. This research will carry out a comparative study and analysis of the evolution of government policies on education and education for citizenship in Argentina, Brazil, Chile, Mexico, and Peru based on the analysis of two variables: (1) public policies for higher education for citizenship and (2) the reception and impact of these policies on public and private universities and their impact on the education system.
Chemical Structure Databases in Drug Discovery
Authors: Gupta Pramodkumar Pyarelal , Bastikar Virupaksha Ajit , Chhajed Santosh Subhash
Published: October 2018

Biologically active and approved molecules have attracted great interest from scientists working in the therapeutic area. This has greatly increased the pressure on the pharma and life science industry in fueling new molecules to the market. Chemical structure database, the backbone of cheminformatics and the bioinformatics industry, has warehoused millions of active and non-active molecules/ligands/derivatives of drug compounds. Numerous public and private chemical databases support the drug discovery projects by contributing their data source in terms of 2D, 3D structure, and annotation reports in development of effective therapeutic projects. In this chapter, the authors discuss important chemical structure databases and their diverse dataset utilization in drug discovery projects.
Facilitating Customer Relationship Management in Modern Business
Authors: Kasemsap Kijpokin
Published: October 2018

This chapter explains the overview of CRM, CRM and technological utilization, and the facilitation of CRM in modern business. CRM is a significant strategy to learn more about customers' needs and behaviors in order to develop the stronger relationships with them. CRM is the most efficient approach in maintaining and creating the relationships with customers in modern business. CRM helps business gain the insight into the behavior of their customers and modify their business operations to ensure that customers are served in the best possible way. CRM also helps business recognize the value of its customers and to capitalize on the improved customer relations. The chapter argues that facilitating CRM has the potential to enhance organizational performance and gain sustainable competitive advantage in modern business.
Synthesis, mechanical and thermal properties of carbon black/epoxy composites
Authors: Bera Tanusree , Acharya S.K. , Mishra Punyapriya
Published: October 2018

In the present work, epoxy/carbon black (CB) composites were made with 1, 2, 3, 4 and 5 wt. % of CB. The tensile test, flexural test, and impact test of the epoxy/CB composites and neat epoxy were performed and, their results were compared. Theresults conclude that the tensile strength, flexural strength, and impact strength of the 4 wt. % of CB composites is better than the other composites and neat epoxy. Thermal graphic analysis (TGA) and differential scanning calorimeter (DSC) of the pure epoxy and composites were calculated and analyzed. The results found that the glass transition (Tg) of the neat epoxy was increased with the addition of CB content up to 4 wt. % and then it was decreased. The decomposition temperature of the composites was increased with the increased in the CB content.Keywords: Carbon black (CB), Epoxy, composites, TGA, DSC, Glass transition temperature (Tg)
INFÂNCIA E CIDADANIA EM CAROLINA DE JESUS E SANDRA MARA HERZER
Authors: Da Silva Santos Doutora Elisângela , Nascimento Dayane Assis
Published: October 2018

Esse artigo tem como objetivo analisar aspectos da chamada literatura marginal, bem como, perceber como a infância é apresentada nas obras de duas autoras: Carolina Maria de Jesus (1914-1977) e Sandra Mara Herzer (1962-1982), que escreveram respectivamente os livros Quarto de Despejo (1960) e A queda para o alto (1983). Trata-se de mulheres, escritoras, poetisas, pobres, marginalizadas, sem oportunidades para usufruir de uma educação formal de qualidade, e que não se conformaram com a realidade que as cercavam. Essas características conectam as histórias de vidas das autoras que retomamos neste texto, cuja temática nos possibilitou enfrentar alguns temas caros à sociedade brasileira, como por exemplo a pobreza, a violência e o racismo. Aqui realizamos um aprofundamento teórico sobre o conceito de Literatura Marginal e como a questão da cidadania, tão requerida pelas autoras, aparece nestas obras, além de apresentarmos a percepção das escritoras sobre a infância e a criança.
The Impact of Service Sectors on Kazakhstan’s Economy
Authors: Han Si Thu , Arefin Sazzadul , Swe Khin Myo
Published: October 2018

This paper investigates the influence of service sectors on gross domestic product (GDP) in Kazakhstan. The aim of this paper to determine the role of services such as tourism, finance, transportation, labor and technology in Kazakhstan’s economy over 1995-2014. The influence of labor force on GDP is significantly positive while technology has insignificant influence on GDP during the study period. The positive and significant effect of labor force in the case of Kazakhstan is consistent with neoclassical theory.
“We Get you to your doorstep!’ An Innovative Strategy for Garuda Airlines?
Authors: Talib Ameen
Published: October 2018

Innovation is the process of developing, creating and implementing new technologies, products and services that result in added value. Garuda Indonesia Airlines is a company that can innovate its’ products/services.This paper looks at Garuda Airlines and proposes a strategy involving innovation of product to increase the airline load factor and regain market share. The proposed strategy is also congruent with the company vision. Keywords: Strategy, Innovation, Garuda
Women Entrepreneurship of Sylhet City, Bangladesh: Challenges & Opportunities
Authors: Julhas Miah Md. , Shahin Alam Khan Md. , Misto Omar Faruk , Rezaul Karim Md.
Published: October 2018

The main purpose of this research is to find out the challenges and opportunities that most of the women specifically those who are entrepreneurs are facing these challenges in Sylhet area, Bangladesh. This report mainly depends on some documents and some practical observations. Women Entrepreneurship is a very essential turning point for the betterment of the women. Unlike the past, women today are no longer confined in the kitchen. They have raised their voice against conservative social outlook. Now women are entering into work force which is providing them a self-identity and right to participate in family decisional affairs. In Sylhet a huge number of women are also having various types of business organizations. The women those who are entrepreneurs of Sylhet, almost 35% are engaged in boutique businesses. There are some other businesses performed by them such as fashion house and cloth store, tailor, parlor, training center etc. Most of them have to maintain their family works despite having a business. But here they are not free from problems. The traditionalism of society, high interest rate of loan, lack of proper training facilities are the main barriers in the smoothness of business. Here every women entrepreneurs recommends that the Government should take necessary effective steps in (providing training, low rate of interest in taking loan etc.) this regard, as it is a very potential way to develop the country.
Incubation Process Case Study
Authors: Shepard Jeffrey
Published: October 2018

The purpose of this case study is to create a profile of business incubators by exploring various aspects concerned with their operations. While tracing the history, development and current practices of business incubators, the aspects explored include the identification of:  the nature of clients served, incubator mission, incubator staffing/personnel, incubator management, incubator resources, and incubator facilities/technology. The main motivation behind this case study is to compile an exhaustive profile of business incubators into one paper.This case study mainly utilized secondary research. By using questionnaires, a survey conducted among managers of selected business incubators in the United States was done. The exploratory nature of this study prompted the use of open ended questions.Findings concerning incubator mission are that current incubators mainly provide professional services of increased complexity as opposed to earlier incubators. Regarding personnel, modern incubators have formal organization structures characterized by the aspect of co-learning. While earlier incubators primarily offered cheap rental space, modern incubators share resources via a complex network of virtual connectivity. On technology, sophisticated technological communication interfaces such as the internet are vital, previous incubators relied on outdated technology. Concerning management, modern incubators require highly adaptive managers capable of addressing specific needs due to the constantly changing business environment. Other findings include the fact that clients are predominantly small business owners and students. Further, managers mainly provide direct services to clients such as mentoring, coaching, and training.
Digital Educational Game Usage Scale: Adapting to Turkish, Validity and Reliability Study
Authors: Sarıgöz Okan , Bolat Yavuz , Alkan Selçuk
Published: October 2018

The purpose of this study is to adapt Digital Educational Games Usage Scale (DEGUS) that was developed byBonanno & Kommers (2008) to Turkish with the companion of a group of university students studying in departmentof English Teaching. In order for scale items to be the same in terms of language, firstly the translations of the itemswere carried out both from English to Turkish and Turkish to English, afterwards examining the forms gathered fromthe students, significant and positive correlations were detected among the data. Exploratory and confirmatory factoranalyses revealed that the scale had four dimensions. In item total correlation calculation of the scale it was observedthat all the items were above .40, item factor loads varied between .51 and .68, Cronbach Alpha internal consistencycoefficient was .78 and test retest correlation was .88. Significant relations were in the calculations regarding thecorrelation analyses of the scale.
The Development of the Text Evaluation Scale for Child Rights: A Study of Validity and Reliability
Authors: Söylemez Yusuf
Published: October 2018

This study was conducted with the aim of developing The Text Evaluation Scale for Child Rights. There are fourdifferent sample chosen for the face validity, content validity and construct validity (for pilot scheme and main study)of the study. For face validity, a sample group of 3 experts chosen with the method of purposeful sampling includingthe researcher was formed. For content validity, snowball method was determined and studied with 12 experts. Forthe study of construct validity, random sampling method was performed for the sample selection in pilot studyinvolving 120 people and in main study involving 510 people.The theoretical framework of the scale was determined by means of the attempts, conventions, studies regarding thesubject basing upon the United Nations Organization Child Rights Convention and additional protocols to thisconvention. One could get minimum 40 and maximum 200 points from the five-point Likert scale which consists of28 positive and 12 negative (total 40) items. The scale has two sub-dimensions which are content and author. Thefact that Cronbach Alpha reliability coefficient is high regarding the sub-dimensions of the scale (authorsub-dimension= 0,822 content sub-dimension= 0,834) shows that the items in the sub-dimensions are consistent withone another. Cronbach Alpha value for the whole of the scale was determined as 0,90 which means that the scale ishighly reliable. Besides, in the scale, there are items of which factor loading value is higher than 0,45. When validityand reliability results are examined, it can be seen that the scale could be utilized to evaluate the text in terms ofbeing suitable for the child rights.
6th Grade Students’ Views about Mathematical Teaching Based on Technology Integration
Authors: Dikkartın Övez Filiz Tuba , Kıyıcı Ozan Deniz
Published: October 2018

The aim of this study is to determine the opinions of 6th grade students towards teaching applications developed onthe basis of Planning-Practicing-Evaluation model which is an ICT integration model for effective mathematicsteaching. While teaching process was designed, Moodle which is a learning management system was used in order touse teaching applications together in a systematic and planned way. Throughout the teaching process, ICT resourcessuch as interactive board, computer, GeoGebra dynamic geometry software, web 2.0 tools (digital stories, videos,animations, games) were used. 33 sixth grade students participated in the research. The case study of qualitativeresearch methods was used in the study. Students' opinions on teaching practices were collected throughsemi-structured interview method. The obtained data were analyzed by content analysis. As a result, it wasdetermined that the students expressed their opinions towards learning practices increases comprehensibility of thesubjects, provides learning opportunities by make and experience, develops positive attitude towards mathematicsteaching, attractive and interesting, they associate daily life with mathematics and increases the desire to participatelessons with having catchy lessons.
An Automatable Method for Determining Adequacy of Thyroid Fine-Needle Aspiration Samples
Authors: Schmolze Daniel B. , Fischer Andrew H.
Published: October 2018

Context.—

Thyroid nodules are a common clinical problem. Cytologic evaluation via fine-needle aspiration is often employed in the diagnostic workup, and rapid on-site assessment of adequacy can help ensure an adequate sample is obtained. However, rapid on-site assessment of adequacy only examines part of the sample, a part that may not then be available for ancillary testing. Moreover, the procedure is time-consuming and poorly reimbursed.

Objective.—

To develop an automatable fluorescence-based image analysis system for assessing the adequacy of thyroid fine-needle aspirations that uses the entire aspirated sample.

Design.—

There were 12 previously diagnosed cases that served as a training set, and 11 cases were used for validation of an image analysis algorithm. The samples were fluorescently stained and imaged using a fluorescent microscope. The images were assessed for adequacy by an image analysis algorithm. Following image analysis, a ThinPrep slide was prepared and blindly scored by a cytopathologist. The standard and computer-derived results were then compared.

Results.—

The algorithm was optimized using the 12 cases in the training set and then applied to the 11 test cases. A total of 8 of 8 adequate samples in the test group were correctly scored as adequate, and 2 of 3 cases that were inadequate were correctly scored as inadequate by the algorithm. One case was erroneously designated as not adequate by the algorithm.

Conclusions.—

Our results demonstrate the feasibility of automating thyroid adequacy assessment using a fluorescent labeling technique followed by computer image analysis.
On Comparing Survival Curves with Right-Censored Data According to the Events Occur at the Beginning, in the Middle and at the End of Study Period
Authors: Karadeniz Pinar Gunel , Ercan Ilker
Published: October 2018

In clinical practice the event of interest does not always occur equally across the study time period. Depending on the disease being investigated, the event that is of interest can occur intensively in different periods of the follow-up time. In such cases, choosing the correct survival comparison test has importance. This study aims to examine and discuss the results of survival comparison tests under some certain circumstances. A simulation study was conducted. We discussed the result of different tests such as Logrank, Gehan-Wilcoxon, Tarone-Ware, Peto-Peto, Modified Peto-Peto tests and tests belonging to Fleming-Harrington test family with (p, q) values; (1, 0), (0.5, 0.5), (1, 1), (0, 1) ve (0.5, 2) by means of Type I error rate that obtained from simulation study, when the event of interest occurred intensively at the beginning of the study, in the middle of the study and at the end of the study time period. As a result of simulation study, Type I error rate of tests is generally lower or higher than the nominal value. In the light of the results, it is proposed to re-examine the tests for cases where events are observed intensively at the beginning, middle and late periods, to carry out new simulation studies and to develop new tests if necessary.
Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation
Authors: Xiao Hui , Huang Rui , Diao Mei , Li Long , Cui XiaoDai
Published: October 2018

Background

Anorectal malformations (ARMs) are the most common congenital malformation of the gut, and regulated by multiple signal transduction pathways. The microRNA (miRNA) expression profiles and their biologial functions in anorectal malformations (ARMs) remain unclear. The aim of our study was to evaluate miRNA and mRNA expression profiles in the ARM rats.

Methods and Materials

ARM was induced with ethylenethiourea (ETU) on gestational day 10. Cesarean deliveries were performed to harvest the embryos on gestional day 20. For the extraction of total RNA, 1 cm terminal hindgut samples were obtained from three fetal rats that had similar weights. The microarrays and quantitative RT-PCR analysis were conducted to evaluate the miRNA and mRNA expression profiles in normal fetal rats (n = 3) and ARM fetal rats (n = 3).

Results

In total, 33 miRNAs and 772 mRNAs were significantly and differentially expressed in terminal hindgut tissues of ARM group versus control group. Functional annotation was performed to understand the functions and pathways of differentially expressed mRNAs. Also, we constructed a miRNA-target gene regulatory network including 25 differentially expressed miRNAs and 76 mRNAs. Furthermore, the credibility of the microarray-based results were validated by using qRT-PCR.

Conclusion

The miRNA and mRNA expression in terminal hindgut tissue of ARM fetal rats might provide a basis for further research on the pathogenesis of ARMs.
Study Offers Insights Into Male HPV Infection’s Potential Role in Infertility
Authors: Youmshajekian Lori
Published: November 2024

This Medical News article discusses new research on how HPV infection in men may affect sperm.
AI Can’t Worry About Patients, and a Clinical Ethicist Says That Matters
Authors: Hswen Yulin , Abbasi Jennifer
Published: November 2024

This Medical News article is an interview with Sarah C. Hull, MD, MBE, a cardiologist and clinical ethicist at Yale School of Medicine, about appropriate boundaries for use of artificial intelligence in clinical settings.
Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire
Authors: Abdel Jawad Mohammad , Jones Philip G. , Arnold Suzanne V. , Cohen David J. , Sherrod Charles F. , Khan Mirza S. , Ikemura Nobuhiro , Chan Paul S. , Spertus John A.
Published: November 2024

Importance

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients.

Objective

To evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies.

Design, Setting, and Participants

A patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023.

Main Outcomes and Measures

Proportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status).

Results

Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively.

Conclusions and Relevance

Inferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.
Crystal structure of β‐d‐galactofuranosidase from Streptomyces sp. JHA19 in complex with an inhibitor provides insights into substrate specificity
Authors: Fujio Noriki , Yamada Chihaya , Kashima Toma , Matsunaga Emiko , Nash Robert J. , Takegawa Kaoru , Fushinobu Shinya
Published: November 2024

d‐Galactofuranose (Galf) is widely distributed in glycoconjugates of pathogenic microbes. β‐d‐Galactofuranosidase (Galf‐ase) from Streptomyces sp. JHA19 (ORF1110) belongs to glycoside hydrolase (GH) family 2 and is the first identified Galf‐specific degradation enzyme. Here, the crystal structure of ORF1110 in complex with a mechanism‐based potent inhibitor, d‐iminogalactitol (Ki = 65 μm) was solved. ORF1110 binds to the C5–C6 hydroxy groups of d‐iminogalactitol with an extensive and integral hydrogen bond network, a key interaction that discriminates the substrates. The active site structure of ORF1110 is largely different from those of β‐glucuronidases and β‐galactosidases in the same GH2 family. A C‐terminal domain of ORF1110 is predicted to be a carbohydrate‐binding module family 42 that may bind Galf. The structural insights into Galf‐ase will contribute to the investigation of therapeutic tools against pathogens.
Large multimodal model‐based standardisation of pathology reports with confidence and its prognostic significance
Authors: Alzaid Ethar , Pergola Gabriele , Evans Harriet , Snead David , Minhas Fayyaz
Published: November 2024

Despite the existence of established standards and guidelines for pathology reporting, many pathology reports are still written in unstructured free text. Extracting information from these reports and formatting it according to a standard is crucial for consistent interpretation. Automated information extraction from unstructured pathology reports is a challenging task, as it requires accurately interpreting medical terminologies and context‐dependent details. In this work, we present a practical approach for automatically extracting information from unstructured pathology reports or scanned paper reports utilising a large multimodal model. This framework uses context‐aware prompting strategies to extract values of individual fields, such as grade, size, etc. from pathology reports. A unique feature of the proposed approach is that it assigns a confidence value indicating the correctness of the model's extraction for each field and generates a structured report in line with national pathology guidelines in human and machine‐readable formats. We have analysed the extraction performance in terms of accuracy and kappa scores, and the quality of the confidence scores assigned by the model. We have also evaluated the prognostic value of the extracted fields and feature embeddings of the raw text. Results showed that the model can accurately extract information with an accuracy and kappa score up to 0.99 and 0.98, respectively. Our results indicate that confidence scores are an effective indicator of the correctness of the extracted information achieving an area under the receiver operating characteristic curve up to 0.93 thus enabling automatic flagging of extraction errors. Our analysis further reveals that, as expected, information extracted from pathology reports is highly prognostically relevant. The framework demo is available at: https://labieb.dcs.warwick.ac.uk/. Information extracted from pathology reports of colorectal cancer cases in the cancer genome atlas using the proposed approach and its code are available at: https://github.com/EtharZaid/Labieb.
High chromosomal instability is associated with higher 10‐year risks of recurrence for hormone receptor‐positive, human epidermal growth factor receptor 2‐negative breast cancer patients: clinical evidence from a large‐scale, multiple‐site, retrospective study
Authors: Liao Yu‐Yang , Fu Jianfei , Lu Xiang , Qian Ziliang , Yu Yang , Zhu Liang , Pan Jia‐Ni , Li Pu‐Chun , Zhu Qiao‐Yan , Li Xiaolin , Sun Wenyong , Wang Xiao‐Jia , Cao Wen‐Ming
Published: November 2024

Long‐term survival varies among hormone receptor‐positive (HR+) and human epidermal growth factor receptor 2‐negative (HER2−) breast cancer patients and is seriously impaired by metastasis. Chromosomal instability (CIN) was one of the key drivers of breast cancer metastasis. Here we evaluate CIN and 10‐year invasive disease‐free survival (iDFS) and overall survival (OS) in HR+/HER2−– breast cancer. In this large‐scale, multiple‐site, retrospective study, 354 HR+/HER2− breast cancer patients were recruited. Of these, 204 patients were used for internal training, 70 for external validation, and 80 for cross‐validation. All medical records were carefully reviewed to obtain the disease recurrence information. Formalin‐fixed paraffin‐embedded tissue samples were collected, followed by low‐pass whole‐genome sequencing with a median genome coverage of 1.86X using minimal 1 ng DNA input. CIN was then assessed using a customized bioinformatics workflow. Three or more instances of CIN per sample was defined as high CIN and the frequency was 42.2% (86/204) in the internal cohort. High CIN correlated significantly with increased lymph node metastasis, vascular invasion, progesterone receptor negative status, HER2 low, worse pathological type, and performed as an independent prognostic factor for HR+/− breast cancer. Patients with high CIN had shorter iDFS and OS than those with low CIN [10‐year iDFS 11.1% versus 82.2%, hazard ratio (HR) = 11.12, p < 0.01; 10‐year OS 45.7% versus 94.3%, HR = 14.17, p < 0.01]. These findings were validated in two external cohorts with 70 breast cancer patients. Moreover, high CIN could predict the prognosis more accurately than Adjuvant! Online score (10‐year iDFS 11.1% versus 48.6%, HR = 2.71, p < 0.01). Cross‐validation analysis found that high consistency (83.8%) was observed between CIN and MammaPrint score, while only 45% between CIN and Adjuvant! Online score. In conclusion, high CIN is an independent prognostic indicator for HR+/HER2− breast cancer with shorter iDFS and OS and holds promise for predicting recurrence and metastasis.
Pharmacokinetics, Efficacy, and Safety of Upadacitinib in Pediatric Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis: An Interim Analysis of an Open‐Label, Phase 1 Trial
Authors: Brunner Hermine I. , Shmagel Anna , Horneff Gerd , Foeldvari Ivan , Antón Jordi , Ramanan Athimalaipet V. , Qian Yuli , Unnebrink Kristina , Hao Shuai , Camp Heidi S. , Khan Nasser , Liu Wei , Mohamed Mohamed‐Eslam F.
Published: November 2024

Objective

This work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular‐course juvenile idiopathic arthritis (pcJIA).

Methods

In an open‐label, phase 1 study (SELECT‐YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received body weight–based upadacitinib doses using a twice‐daily oral solution or once‐daily extended‐release tablet based on their body weight and ability to swallow tablets. The study included a 7‐day pharmacokinetic assessment, followed by a long‐term efficacy and safety evaluation for up to 156 weeks, including an additional long‐term safety cohort. This interim analysis included available pharmacokinetic and safety data and efficacy data collected through week 48.

Results

A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately three hours and one hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half‐life was approximately five hours and two hours, respectively. Juvenile idiopathic arthritis American College of Rheumatology 30, 50, 70, 90, and 100 responses at week 12 were 91.8%, 89.8%, 69.4%, 49.0%, and 32.7%, respectively. Efficacy was generally maintained through week 48, and improvement in additional efficacy end points was also observed. At a median exposure duration of 412 days, 52 of 57 patients reported adverse events; of these, 6 experienced serious adverse events. Adverse events were predominately mild to moderate in severity and consistent with the known safety profile of upadacitinib.

Conclusion

This interim analysis demonstrates that the bodyweight‐based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.
Innovative Vibration Control of Triply Periodic Minimum Surfaces Lattice Structures: A Hybrid Approach with Constrained Layer Damping Silicone–Viscoelastic Layer Integration
Authors: Ozden Murat Can , Simsek Ugur , Ozdemir Mirhan , Gayir Cemal Efe , Sendur Polat
Published: November 2024

This article introduces a novel method to enhance the damping performance of triply periodic minimal surface (TPMS) structures by integrating metamaterials with constrained layer damping (CLD) applications. This objective is accomplished by combining a viscoelastic silicone polymer layer with a primitive TPMS structure fabricated through laser powder bed fusion using aluminum alloy powder. Finite‐element method (FEM) models using voxel elements, due to their high accuracy and computational efficiency, are developed to analyze the damping behavior of the TPMS‐based CLD structure across various frequencies. Experimental modal test results validate the FEM model with high accuracy. Two distinct damping characterization methods, both time‐domain and frequency‐based, are employed to quantify the damping performance. The results reveal a fivefold improvement in damping performance in the time domain compared to the metal TPMS structure. In the frequency domain, the structure demonstrates 76% lower cumulative vibration compared to the metallic reference using the integral of frequency response method.
Multifunctional Reconfigurable Vanadium Dioxide Integrated Metasurface for Reflection, Asymmetric Transmission and Cross‐Polarization Conversion in Terahertz Region
Authors: Nguyen Thi Quynh Hoa , Nguyen Thi Minh
Published: November 2024

Integrating reconfigurable and diverse functionalities into a single metasurface at terahertz (THz) frequencies is an emerging research topic that faces significant challenges. Here, a reconfigurable THz metasurface is proposed, offering diversified functionalities based on the phase transition of vanadium dioxide (). The proposed metasurface can switch from wideband reflection to wideband cross‐polarization conversion (CPC) and asymmetric transmission (AT) for linearly polarized waves. When is in its fully metallic state, the metasurface efficiently reflects normally incident waves ranging from 0.2 to 2.8 THz, with total reflection exceeding 0.8. When is in its insulating state, the metasurface achieves nearly perfect wideband cross‐polarization conversion with CPC efficiency above 0.99 from 0.46 to 2.67 THz, and excellent AT effect with efficiency over 0.9 from 0.65 to 2.29 THz for normal incidence of linearly polarized waves. Moreover, the high efficiency of CPC and AT effects is maintained over a wide range of incident angles. The proposed switchable metasurface with diverse functionalities is expected to enable cutting‐edge research and innovative applications in THz communication, sensing, and imaging.
Acoustic Tunable Battery‐Free Implants Based on Sustainable Triboelectric Nanogenerators With Metal‐Polymer Intermixing Layers
Authors: Chung Youngwook , Yuan Hongwei , Wang Ze , Jeong Jang‐Mook , Park Byung‐Joon , Hwang Joon‐Ha , Suh Su‐Jeong , Choi Byung‐Ok , Park Hyun‐moon , Kim Young‐Jun , Dai Keren , Kim Sang‐Woo
Published: November 2024

Ultrasound‐driven triboelectric nanogenerators (US‐TENGs) offer an innovative solution for transcutaneous power transfer, with the potential to enable battery‐free, permanently implantable electronics. However, research to date has primarily demonstrated only fragmentary functionalities for these applications. This work presents the simultaneous transmission of acoustic power and precise acoustic information using a double‐electrode US‐TENG, enabling a battery‐free implant controlled via ultrasound. High and sustained output from a US‐TENG is crucial for operating the versatile system; therefore, a novel triboelectric membrane with a top electrode incorporating a gold‐polymer intermixing layer has been designed. Reversible micro‐cracks form in the intermixing layer, ensuring electrical connectivity under high‐frequency strain. In vivo experiments confirm that the system is biocompatible and can be reliably operated inside living rats. These achievements represent a significant step toward realizing multifunctional implantable electronics that can be reliably powered and controlled by ultrasound.
Long‐Term Single‐Molecule Tracking in Living Cells using Weak‐Affinity Protein Labeling
Authors: Catapano Claudia , Dietz Marina S. , Kompa Julian , Jang Soohyen , Freund Petra , Johnsson Kai , Heilemann Mike
Published: November 2024

Single‐particle tracking (SPT) has become a powerful tool to monitor the dynamics of membrane proteins in living cells. However, permanent labeling strategies for SPT suffer from photobleaching as a major limitation, restricting observation times, and obstructing the study of long‐term cellular processes within single living cells. Here, we use exchangeable HaloTag Ligands (xHTLs) as an easy‐to‐apply labeling approach for live‐cell SPT and demonstrate extended observation times of individual living cells of up to 30 minutes. Using the xHTL/HaloTag7 labeling system, we measure the ligand‐induced activation kinetics of the epidermal growth factor receptor (EGFR) in single living cells. We generate spatial maps of receptor diffusion in cells, report non‐uniform distributions of receptor mobility, and the formation of spatially confined ‘hot spots’ of EGFR activation. Furthermore, we measured the mobility of an ER‐luminal protein in living cells and found diffusion coefficients that correlated with the ER nano‐structure. This approach represents a general strategy to monitor protein mobility in a functional context and for extended observation times in single living cells.
Karl Ziegler – Early Career of a Scientist
Authors: Kießling Christoph
Published: November 2024

Karl Ziegler is considered one of the most outstanding chemists of the 20th century. In particular, his work on organometallic mixed catalysts, which allows the polymerization of ethylene at normal pressure, led to a revolution in plastics production and changed the everyday life of all mankind. In 1963, he was awarded the Nobel Prize in Chemistry for this work, together with Giulio Natta. This article focuses on Ziegler's early career, which has received little attention to date. It describes his youth and study years in Marburg, which partly coincide with the First World War. Subsequently, his postdoctoral period is examined, which led him via Marburg and Frankfurt to his first associate professorship in Heidelberg. Special attention is paid to his relationship to National Socialism, which he opposed. As a result, Ziegler experienced professional difficulties in the 1930s, such as repeated rejection when filling various professorships. His appointment as a full professor in Halle and his subsequent directorship at the Max‐Planck‐Institut für Kohlenforschung (Coal Research), where he finally achieved his greatest research achievement, are described in the following.