bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib
Authors: McWilliams Emily M. , Lucas Christopher R. , Chen Timothy , Harrington Bonnie K. , Wasmuth Ronni , Campbell Amanda , Rogers Kerry A. , Cheney Carolyn M. , Mo Xiaokui , Andritsos Leslie A. , Awan Farrukh T. , Woyach Jennifer , Carson William E. , Butchar Jonathan , Tridandapani Susheela , Hertlein Erin , Castro Carlos E. , Muthusamy Natarajan , Byrd John C. 
Published: February 2019

Abstract
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment. Blocking BAFF interaction with BAFF-R by using VAY-736, a humanized defucosylated engineered antibody directed against BAFF-R, antagonized BAFF-mediated apoptosis protection and signaling at the population and single-cell levels in CLL cells. Furthermore, VAY-736 showed superior antibody-dependent cellular cytotoxicity compared with CD20- and CD52-directed antibodies used in CLL. VAY-736 exhibited in vivo activity as a monotherapy and, when combined with ibrutinib, produced prolonged survival compared with either therapy alone. The in vivo activity of VAY-736 is dependent upon immunoreceptor tyrosine–based activation motif (ITAM)–mediated activation of effector cells as shown by using an ITAM-deficient mouse model. Collectively, our findings support targeting the BAFF signaling pathway with VAY-736 to more effectively treat CLL as a single agent and in combination with ibrutinib.
Epidermal growth factor receptor (EGFR) overexpression in triple-negative breast cancer: association with clinicopathologic features and prognostic parameters
Authors: Hashmi Atif Ali , Naz Samreen , Hashmi Shumaila Kanwal , Irfan Muhammad , Hussain Zubaida Fida , Khan Erum Yousuf , Asif Huda , Faridi Naveen 
Published: February 2019

Abstract
Introduction
Triple-negative breast cancers are a poor prognostic group of breast cancers that don’t respond to conventional hormonal and her2neu targeted therapy. A subset of triple-negative breast cancer is known to overexpress epidermal growth factor receptor (EGFR); however prognostic significance of this biomarker has not been widely studied in our population. Therefore, we aimed to evaluate the frequency of EGFR overexpression in triple-negative breast cancer in our setup and its association with prognostic and predictive factors.

Methods
We performed EGFR immunohistochemistry on 150 cases of triple-negative breast cancers. Intensity and percentage of EGFR expression were combined to formulate an EGFR score, that was compared with prognostic features of breast cancer and recurrence status of patients.

Results
Positive EGFR expression was noted in 18.7% ( 28 cases); out of which 16% (24 cases) showed low EGFR expression, whereas high EGFR expression was seen in 2.7% ( 4 cases). No significant association of EGFR expression was noted when compared with various clinicopathological parameters and recurrence status of the patients.

Conclusion
We found EGFR protein expression in 18.7% of cases while high expression was seen in only 2.7 % cases of triple-negative breast cancer which may harbor underlying genetic alterations like altered EGFR gene copy number, chromosome 7 copy number or average EGFR gene: chromosome 7 ratio; therefore we suggest that molecular tests like FISH to evaluate these EGFR molecular alterations should be performed in EGFR over expressing triple negative breast cancers in our setup to identify patients that can benefit from anti-EGFR targeted therapy. Moreover, regional difference in EGFR expression (high expression in chinese population compared to our population) are may be due to different underlying genetic alterations in triple-negative breast cancers, further necessitating a need of devising personalized therapeutic protocols for locoregional population.
Cost per insertion and couple year of protection for postpartum intrauterine devices and implants provided during service scale-up in Kigali, Rwanda
Authors: Wall Kristin M. , Ingabire Rosine , Allen Susan , Karita Etienne 
Published: February 2019

Introduction: In two high-volume government hospitals, their two affiliated health facilities, and two additional health facilities, we developed and implemented postpartum intrauterine device (PPIUD) and postpartum (PP) implant promotional counseling and service delivery procedures between May-July 2017 in Kigali, Rwanda. Between August 2017 and July 2018, 9,073 pregnant women received PPIUD/PP implant promotions who later delivered in one of our selected facilities. Of those, 2,633 had PPIUDs inserted, and 955 had PP implants inserted. The goal of the present analysis is to detail implementation expenditures and estimate incremental costs per insertion and couple years of protection (CYP) for PPIUD and PP implant users. Methods: We detail the incremental costs during the implementation from the health system perspective (including both the implementation costs and the cost of contraceptive methods) and use of standard methods to estimate the cost per insertion and CYP for PPIUD and PP implant users. In addition to the incremental costs of labor and supplies, the costs of promotional activities are included. Research costs for formative work were excluded. Results: A total of $74,147 USD was spent on the implementation between August 2017 and July 2018. The largest expense (34% of total expenses) went toward personnel, including doctoral-level, administrative, data management and nurse counseling staff. Training for PPIUD and implant providers and promoters comprised 8% of total expenses. Recruitment and reimbursements comprised 6% of expenses. Costs of implants to the government comprised 12% of the expenses, much higher than the cost of IUDs (1%). Costs per insertion were $25/PPIUDs and $77/PP implant. Costs per CYP were $5/PPIUDs and $20/PP implant. Conclusion: Understanding the cost per PPIUD/PP implant inserted and CYP can help to inform the cost of scaling up PPIUD/PP implant service implementation activities and resource allocation decision-making by the Rwandan Ministry of Health.
Optimisation and standardisation of a multiplex immunoassay of diverse Plasmodium falciparum antigens to assess changes in malaria transmission using sero-epidemiology
Authors: Wu Lindsey , Hall Tom , Ssewanyana Isaac , Oulton Tate , Patterson Catriona , Vasileva Hristina , Singh Susheel , Affara Muna , Mwesigwa Julia , Correa Simon , Bah Mamadou , D'Alessandro Umberto , Sepúlveda Nuno , Drakeley Chris , Tetteh Kevin K A 
Published: February 2019

Background: Antibody responses have been used to characterise transmission and exposure history in malaria-endemic settings for over a decade. Such studies have typically been conducted on well-standardised enzyme-linked immunosorbent assays (ELISAs). However, recently developed quantitative suspension array technologies (qSAT) are now capable of high-throughput and multiplexed screening of up to hundreds of analytes at a time. This study presents a customised protocol for the Luminex MAGPIX© qSAT using a diverse set of malaria antigens. The aim is to develop a standardised assay for routine serological surveillance that is implementable across laboratories and epidemiological settings. Methods: A panel of eight Plasmodium falciparum recombinant antigens, associated with long- and short-lived antibody responses, was designed for the Luminex MAGPIX© platform. The assay was optimised for key steps in the protocol: antigen-bead coupling concentration, buffer composition, serum sample dilution, and bead storage conditions. Quality control procedures and data normalisation methods were developed to address high-throughput assay processing. Antigen-specific limits of quantification (LOQs) were also estimated using both in-house and WHO reference serum as positive controls. Results: Antigen-specific bead coupling was optimised across five serum dilutions and two positive controls, resulting in concentrations operational within stable analytical ranges. Coupled beads were stable after storage at room temperature (22⁰C) for up to eight weeks. High sensitivity and specificity for distinguishing positive and negative controls at serum sample dilutions of 1:500 (AUC 0.94 95%CI 0.91-0.96) and 1:1000 (AUC 0.96 95%CI 0.94-0.98) were observed. LOQs were also successfully estimated for all analytes but varied by antigen and positive control. Conclusions: This study demonstrates that developing a standardised malaria-specific qSAT protocol for a diverse set of antigens is achievable, though further optimisations may be required. Quality control and data standardisation methods may also be useful for future analysis of large sero-epidemiological surveys.
Skin cancer
Authors: Peate Ian 
Published: February 2019

Skin cancer is a common type of cancer. The healthcare assistant and assistant practitioner (HCA and AP) are in an ideal position to recognise abnormal skin conditions and to report these. In order to do this, there is a need to have an understanding of the anatomy and physiology of the skin. This article provides an overview of the anatomy and physiology of the skin; for completeness, this article also includes the appendages (the glands, hair and nails). This article provides the incidence of skin cancer, the various risk factors, along with information concerning health promotion. The signs and symptoms are outlined and the methods of diagnosis are discussed. The various treatment options are described. A glossary of terms has been included, along with five multiple-choice questions provided to promote learning and application in practice.
Unindo Mundos: A Screenwriting Research Network Conference
Authors: Castro Maria Guilhermina 
Published: February 2019

Em setembro de 2018, a 11.ª edição da Screenwriting Research Network Conference teve lugar na Università Cattolica del Sacro Cuore de Milão. Entres as diversas atividades de pré-conferência e conferência, salientam-se tendências como o estudo das séries TV, a investigação practice-based, análise fílmica quantitativa ou processos de escrita e criação.
Validation of the Greek version of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire
Authors: Drosatou Chrysoula , Vlachopapadopoulou Elpis-Athina , Bullinger Monika , Quitmann Julia , Silva Neuza , Salemi Georgia , Pavlopoulou Ioanna , Michalacos Stefanos , Tsoumakas Konstantinos 
Published: February 2019

Abstract

Background
The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a condition-specific instrument for measuring the health-related quality of life (HRQoL) in short statured children/adolescents from patients’ and parents’ perspectives. The aim of this study was to investigate the psychometric properties of the Greek version of the QoLISSY questionnaire.

Methods
The original European QoLISSY scales were translated into Greek following the guidelines for linguistic validation and applied to 184 dyads of children 8–18 years old and their parents, as well as to 14 parents of children 4–7 years old in Greece. The field testing responses to the Greek version of QoLISSY were analyzed.

Results
The qualitative analysis of the Greek data provided results consistent with the European sample. The subsequent field test showed acceptable internal consistency (Cronbach α between 0.67–0.93) and high test-retest reliability (intraclass correlation coefficients [ICC] ≥0.70). Correlations with the generic KIDSCREEN questionnaire indicated good convergent validity. Confirmatory factor analysis (CFA) also yielded acceptable results. Higher HRQoL for taller children suggests that QoLISSY was able to detect significant height-related differences.

Conclusions
The Greek version of the QoLISSY questionnaire is psychometrically sound and its use is recommended in further clinical research to ascertain the impact of short stature (SS) and treatments in Greek children/adolescents and families.
Dynamical Mechanical Properties of Polypropylene Composites Filled with Olive Pit Particles
Authors: Gümüş Beril Eker , Yağci Özlem , Erdoğan Duygu Ceylan , Taşdemir Münir 
Published: February 2019

Abstract
Wood Polymer Composites (WPCs) have attracted attention in recent years because of growing ecological, social, and economic awareness. This study focuses on polymer composites filled with olive pit particles. In the present study, the test specimens were prepared with different ratios of mixtures that contain polypropylene (PP), olive pit particles in four different concentrations (5.0, 10.0, 15.0, and 20.0 wt%), and maleic anhydride as modifier. The mechanical, thermal, and viscoelastic properties of the WPC were obtained using Dynamic Mechanic Analyzer test equipment and a thermogravimetric differential thermal analyzer. Fourier transform infrared spectroscopy was carried out in order to determine the chemical bonds of these materials. The specimens were also characterized by scanning electron microscopy. The results of the study demonstrated that olive pit particles could be used as reinforcement for PP because of their good thermal and mechanical effects.
Interrelationship of Thermal Effects on Calcium Sulfate Dihydrate Casts Containing Borax and Kaolin: Differential Thermal Analysis (DTA), Thermogravimetric Analysis (TGA), and Contact Dilatometry
Authors: Engbrecht Dick C. , Hirschfeld Deidre A. 
Published: February 2019

Abstract
The core composition of gypsum wallboard is calcium sulfate dihydrate (CaSO4·2H2O) with varying impurities, additives, or both. This study compares two commercially calcined sources of hemihydrate (CaSO4·½H2O) from a natural source and a synthetic by-product of flue gas desulfurization and neutralization to reagent grade hemihydrate. Two common ingredients, borax and kaolin, are mixed into a slurry with distilled water. The analysis supports the hypothesis that minor components in the cast have an effect on the high temperature performance of gypsum casts. The analysis is enhanced when the differential thermal analysis, thermogravimetric analysis, and dilatometry data are combined to study the changes in density versus heat flow. Specifically, the thermal performance is affected by (1) the impurities found in hemihydrate sources; (2) during the fluidization phase, the reaction of borax with free Ca++ ions to form new borate salts that melt at lower temperatures; and (3) the intercalation of these and other ions with kaolin, providing thermal stability by reducing the formation of thermally active salts.
Pengaruh Investasi, Laju Pertumbuhan Ekonomi, dan Upah Terhadap Penyerapan Tenaga Kerja
Authors: Wildan Wildan 
Published: February 2019

This study aims to Influence Investment, Economic Growth Rate, and Wages Against Absorption of Employment in Bogor Regency with the research method used in this study is a quantitative descriptive research method. The data used are secondary data which are analyzed by the quantitative method of multiple linear regression using the Ordinary Least Square (OLS) method. While the model used in this study is a model of the employment absorption function with 3 independent variables and 1 dependent variable. Based on the results of processed data using regression regarding the effect of investment, the rate of economic growth, and wages on labor absorption in Bogor Regency, it can be concluded that investment does not have a significant effect on employment in Bogor Regency. The economic growth rate has a positive and significant effect on employment in Bogor Regency. Wages have a positive and significant effect on employment in Bogor Regency. Simultaneously investment, economic growth rate, and wages show a significant influence on employment in Bogor Regency.

Penelitian ini bertujuan untuk Pengaruh Investasi, Laju Pertumbuhan Ekonomi, dan Upah Terhadap Penyerapan Tanaga Kerja di Kabupaten Bogor dengan metode penelitian yang dipakai dalam penelitian ini adalah metode penelitian deskriptif kuantitatif. Data yang digunakan adalah data sekunder yang dianalisis dengan metode kuantitatif regresi linear berganda dengan metode Ordinary Least Square (OLS). Sedangkan Model yang digunakan dalam penelitian ini adalah model fungsi penyerapan tenaga kerja dengan 3 variabel independen dan 1 variabel dependen. Berdasarkan hasil data yang telah diolah menggunakan regresi mengenai pengaruh investasi, laju pertumbuhan ekonomi, dan upah terhadap penyerapan tenaga kerja di Kabupaten Bogor, dapat ditarik kesimpulan bahwa investasi tidak berpengaruh signifikan terhadap penyerapan tenaga kerja di Kabupaten Bogor. Laju pertumbuhan ekonomi berpengaruh positif dan signifikan terhadap penyerapan tenaga kerja di Kabupaten Bogor. Upah berpengaruh positif dan signifikan terhadap penyerapan tenaga kerja di Kabupaten Bogor. Secara simultan investasi, laju pertumbuhan ekonomi, dan upah menunjukkan pengaruh yang signifikan terhadap penyerapan tenaga kerja di Kabupaten Bogor.
A Large Scale Systemic RNAi Screen in the Red Flour BeetleTribolium castaneumIdentifies Novel Genes Involved in Insect Muscle Development
Authors: Schultheis Dorothea , Weißkopf Matthias , Schaub Christoph , Ansari Salim , Dao Van Anh , Grossmann Daniela , Majumdar Upalparna , Hakeemi Muhammad Salim , Troelenberg Nicole , Richter Tobias , Schmitt-Engel Christian , Schwirz Jonas , Ströhlein Nadi , Teuscher Matthias , Bucher Gregor , Frasch Manfred 
Published: February 2019

AbstractAlthough muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other insects. To help in closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-EGFP tester strains. Injections into pupae were followed by the analysis of the late embryonic/early larval muscle patterns, and injections into larvae by the analysis of the adult thoracic muscle patterns. Herein we describe the results of the first-pass screens with pupal and larval injections, which covered ∼8,500 and ∼5,000 genes, respectively, of a total of ∼16,500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded phenotypes in larval body wall and leg muscles as well as in indirect flight muscles. We then present the main candidates from the pupal injection screen that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.
T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy
Authors: Winterberg Pamela D. , Robertson Jennifer M. , Kelleman Michael S. , George Roshan P. , Ford Mandy L. 
Published: February 2019

Significance Statement
Uremic cardiomyopathy, which features left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, predicts mortality in patients with CKD. In this study, the authors present findings supporting emerging evidence that T cells play a causal role in diastolic dysfunction during CKD. In a mouse model of CKD, they demonstrate that T cells infiltrate the heart and lead to diastolic dysfunction and impaired ventricular strain, whereas depletion of T cells improves diastolic function and myocardial strain. They also show that in children with CKD, increasing frequency of T cells bearing markers of sustained activation (PD-1 and CD57) is associated with echocardiographic indications of worsening diastolic function. Future research may inform novel therapies that target T cell function to mitigate early subclinical myocardial dysfunction during CKD.

Background
Uremic cardiomyopathy, characterized by left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, contributes to increased cardiovascular mortality in patients with CKD. Emerging evidence suggests a pathogenic role for T cells during chronic heart failure.

Methods
To determine whether T cells contribute to uremic cardiomyopathy pathogenesis, we modeled this condition by inducing CKD via 5/6th nephrectomy in mice. We used flow cytometry to assess expression of markers of T cell memory or activation by lymphocytes from CKD mice and controls, as well as lymphocyte capacity for cytokine production. Flow cytometry was also used to quantify immune cells isolated from heart tissue. To test effects of T cell depletion on cardiac function, we gave CKD mice anti-CD3 antibody injections to deplete T cells and compared heart function (assessed by echocardiography) with that of controls. Finally, we correlated T cell phenotypes with structural and functional measures on clinically acquired echocardiograms in children with CKD.

Results
Mice with CKD accumulated T cells bearing markers of memory differentiation (CD44hi) and activation (PD-1, KLRG1, OX40), as reported previously in human CKD. In addition, mice with CKD showed T cells infiltrating the heart. T cell depletion significantly improved both diastolic function and myocardial strain in CKD mice without altering hypertension or degree of renal dysfunction. In children with CKD, increasing frequency of T cells bearing activation markers PD-1 and/or CD57 was associated with worsening diastolic function on echocardiogram.

Conclusions
CKD results in an accumulation of proinflammatory T cells that appears to contribute to myocardial dysfunction.