bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling in muscle‐invasive bladder cancer: more than the sum of its parts
Authors: Sjödahl Gottfrid , Jackson Chelsea L , Bartlett John MS , Siemens D Robert , Berman David M 
Published: January 2019

AbstractBladder cancers are biologically and clinically heterogeneous. Recent large‐scale transcriptomic profiling studies focusing on life‐threatening muscle‐invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these clusters reflect intrinsic urothelial cell‐type differentiation programs, including those with luminal and basal cell characteristics. Also like breast cancer, each cell‐based subtype demonstrates a distinct profile with regard to its prognosis and its expression of therapeutic targets. Indeed, a number of studies suggest subtype‐specific differential responses to cytotoxic chemotherapy and to therapies that inhibit a number of targets, including growth factors (EGFR, ERBB2, FGFR) and immune checkpoint (PD1, PDL1) inhibitors. Despite burgeoning evidence for important clinical implications, subtyping has yet to enter into routine clinical practice. Here we review the conceptual basis for intrinsic cell subtyping in muscle‐invasive bladder cancer and discuss evidence behind proposed clinical uses for subtyping as a prognostic or predictive test. In deliberating barriers to clinical implementation, we review pitfalls associated with transcriptomic profiling and illustrate a simple immunohistochemistry (IHC)‐based subtyping algorithm that may serve as a faster, less expensive alternative. Envisioned as a research tool that can easily be translated into routine pathology workflow, IHC‐based profiling has the potential to more rapidly establish the utility (or lack thereof) of cell type profiling in clinical practice. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
3D‐Drucken mit Metallen
Authors: Reznik Daniel , Kastsian Darya , Lüthen Volkmar , Krüger Ursus 
Published: January 2019

ZusammenfassungFür das 3D‐Drucken von Metallbauteilen eignet sich das Selektive Laserstrahlschmelzen (SLM). SLM fällt unter die additiven Fertigungstechniken, die eine digitale Produktion nach der Industrie 4.0‐Vision ermöglichen sollen. Die SLM führt einen starken Laserstrahl über ein Bett aus Metallpulver. In der obersten Schicht schmilzt dieser kleine Schweißbahnen in Form des Werkstücks, dann schiebt eine Rakel eine neue Pulverschicht darüber. So entsteht schichtweise das Werkstück. Die erforderlichen hohen Temperaturen im Laserfokus sorgen allerdings für einen thermomechanischen Verzug, der insbesondere bei komplexen Geometrien eine Herausforderung darstellt. Eine Prozesssimulation soll Designer so unterstützen, dass das Werkstück in den gewünschten Maßen ohne intolerable geometrische Fehler, Risse und mit optimal geringer Porosität entsteht. Die Simulation muss die Makroskala des Werkstücks mit der Mesoskala der lokalen Schmelzbadumgebung so verbinden, dass praktikable Rechenzeiten erreichbar sind.
A validated liquid chromatography/tandem mass spectrometry method for 4,4′‐methylenedianiline quantitation in human urine as a measure of 4,4′‐methylene diphenyl diisocyanate exposure
Authors: Lépine Maggy , Sleno Lekha , Lesage Jacques , Gagné Sébastien 
Published: January 2019

Rationale4,4′‐Methylene diphenyl diisocyanate (MDI) is a highly reactive isocyanate used in the production of polyurethanes. Workers exposed to these products may develop sensitization to the diisocyanate compounds, leading to occupational asthma. Quantifying MDI levels is necessary to ensure workplace safety. MDI is metabolized by acetylation and/or conjugation to macromolecules for excretion into urine. All metabolites can be chemically hydrolyzed to form the free diamine 4,4′‐methylenedianiline (MDA) as a urinary biomarker of MDI exposure. Current methods involve long sample preparation, or have been designed using costly automation. There is therefore a need to develop a new practical method for assessing exposure to MDI.MethodsUrine samples were acidified and heated to form MDA, followed by neutralization and liquid–liquid extraction. Extracts were separated by reversed‐phase chromatography on a HSS T3 column followed by analysis on a triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode.Results13C15N‐MDA was selected as the internal standard (IS) of choice following an investigation of internal standard stability. The hydrolysis efficiency, forming free MDA from conjugated metabolites in vivo, was evaluated using 4,4′‐methylenebis(acetanilide) spiked into urine and complete hydrolysis occurred after 1 h. A dynamic range of 5 to 500 nM was achieved, and was useful for monitoring MDI exposure considering the biological guidance value (BGV) of 10 μg/L (~50 nM) proposed by the German Research Foundation (DFG). The limit of detection (LOD) and limit of quantification (LOQ) of the method were 0.8 and 2.7 nM, respectively. The intra‐day and inter‐day precisions were 4.33% and 4.27%, respectively. Finally, the method was tested with inter‐laboratory samples from the German External Quality Assessment Scheme (G‐EQUAS) program and the results submitted were all within the allowable tolerance range.ConclusionsA practical and validated method for the analysis of small‐ to medium‐sized batches of samples has been developed for the biological monitoring of MDI exposure in human urine.
Random‐start ovarian stimulation with aromatase inhibitor for fertility preservation in women with Japanese breast cancer
Authors: Nakasuji Takashi , Kawai Kiyotaka , Ishikawa Tomonori , Teraoka Kaori , Takeuchi Shiho , Miyagawa Tomoko , Nara Kazuko , Kidera Nobuyuki , Harada Tatsuya , Miyasaka Naoyuki 
Published: January 2019

AbstractPurposeFertility preservation is an important issue for young cancer patients. Random‐start controlled ovarian stimulation and double ovarian stimulation have been proposed for efficient oocyte retrieval within the limited time before cancer therapy. We aimed to clarify the efficacy of these new protocols within the Japanese population.MethodsWe performed a retrospective observational study at a multicenter from February 2012 to August 2017. The study entailed 50 cycles with 34 patients who underwent fertility preservation due to breast cancer. Follicular phase or luteal phase ovarian stimulation with aromatase inhibitor was performed. A second ovarian stimulation was started with or without waiting until the next menstruation. We measured the number of retrieved oocytes and cryopreserved oocytes/embryos, the ratio of mature oocytes, and the fertilization rate.ResultsThe numbers of retrieved oocytes and frozen oocytes/embryos were not significantly different between follicular phase and luteal phase ovarian stimulation. The number of retrieved oocytes was not reduced at the second ovum pick up compared to the first ovum pick up in the double ovarian stimulation.ConclusionsRandom‐start controlled ovarian stimulation and double ovarian stimulation with aromatase inhibitor for breast cancer patients were effective protocols for retrieving a greater number of oocytes within the limited time.
Critical success factors for implementing building information modeling and sustainability practices in construction projects: A Delphi survey
Authors: Olawumi Timothy O. , Chan Daniel W.M. 
Published: January 2019

AbstractThe research study aims to explore and assess the critical success factors (CSFs) that can amplify the integration of building information modeling (BIM) and sustainability practices in construction projects. Delphi survey technique was employed to solicit the perceptions of experts on the 30 identified CSFs by means of a two‐round Delphi survey. The expert panel responses were analyzed using descriptive and inferential statistical tools. The key drivers identified in the study are related to people‐centric, and data and technology‐centric interventions in the built environment. Crucial deductions were formed on the basis of a comparative analysis of the expert groups. The study's findings have provided valuable lessons for local authorities, policymakers, and project stakeholders to strengthen the drive for achieving full adoption of green BIM initiatives. The study has also provided effective recommendations for increasing the uptake of BIM and sustainability practices in the construction industry, and has contributed to the existing body of knowledge about smart urbanization and hands‐on practice in the built environment.
Enhanced Catalytic Performance for CO2 Hydrogenation to Methanol over N‐doped Graphene Incorporated Cu‐ZnO‐Al2O3 Catalysts
Authors: Ma Qingxiang , Geng Mengqian , Zhang Jianli , Zhang Xiangling , Zhao Tian‐Sheng 
Published: January 2019

AbstractN‐doped graphene (NG) incorporated Cu‐ZnO‐Al2O3 (CZA) catalysts were prepared by co‐precipitation method and their catalytic performances for CO2 hydrogenation to methanol were evaluated under the reaction conditions of 200 ○C and 3.0 MPa. The results indicate that NG promotes effectively the dispersion of CZA and changes the electron structure of CZA, which could provide synergistic effect for methanol synthesis. When NG content is 10 wt.%, the CO2 conversion and methanol selectivity can achieve the highest values of 8.2% and 84%, respectively, which are much higher than those of traditional CZA catalyst.
One‐Pot Cleavage of Aryl Alkyl Ethers by Aluminum and Iodine in Acetonitrile
Authors: Tian Juan , Yue Huaxin , Yang Pengtao , Sang Dayong 
Published: January 2019

AbstractCleavage of aryl alkyl ethers was conducted in a one‐pot one‐stage manner by mixing the ethers, aluminum and iodine in acetonitrile without the in situ preparation of aluminum triiodide in advance. For ethers bearing acid‐labile functional groups such as allyl, alkenyl and carbonyl, an acid scavenger (calcium oxide, 1,3‐diisopropylcarbodiimide or dimethyl sulfoxide) was used to prevent side‐reactions. This one‐pot protocol is efficient and convenient for the removal of methyl, ethyl, isopropyl and tert‐butyl groups from typical aryl alkyl ethers, catechol monomethyl and dimethyl ethers, and is compatible with a variety of functional groups including alkenyl, alkyl, allyl, amido, cyano, formyl, halogen, keto and nitro group. Methyl 2‐anisate and eugenol acetate were exhaustively deprotected by the method that afforded salicylic acid and hydroxychavicol, respectively.
Design and Synthesis of Tetrandrine Derivatives as Potential Anti‐tumor Agents Against A549 Cell Lines
Authors: Niu Nana , Jin Tao , Li Xia , Xu Jinfang , Qu Tingli , Bodwell Graham J. , Zhao Zhengbao 
Published: January 2019

AbstractTetrandrine (1) was converted to 5‐bromotetrandrine (2) using a mild oxidative system (DMSO/HBr). Suzuki‐Miyaura and Sonogashira cross‐coupling reactions were then employed to yield a set of 5‐substituted tetrandrine derivatives. A total of 19 new compounds was synthesized and they were characterized by 1H NMR, 13C NMR and HRMS. Their antiproliferative activities against A549 cell lines in vitro were evaluated using the MTT assay. Most of the compounds were found to possess significant inhibitory activities and compound 7 had the highest (IC50 = 3.04 μM). Further studies on the mechanism demonstrated by compound 7 showed that it promotes apoptosis of A549 cells in a dose‐dependent manner and reduces the mitochondrial membrane potential. Western blot results showed that the compound up‐regulated the levels of Bax protein and down‐regulated the level of Bcl‐2 protein. Compared to the control group, the expression of cleaved‐caspase 3 and cleaved‐PARP in cells was significantly increased.
Performance of PVC/SiO2 nanocomposites under thermal ageing
Authors: Habashy Mohamed M. , Abd-Elhady Amr M. , Elsad R. A. , Izzularab Mohamed A. 
Published: January 2019

AbstractAccelerated thermal ageing test on nanocomposites of polyvinyl chloride (PVC/SiO2) is conducted at constant temperatures of 110 °C and 140 °C. Accordingly, different PVC/SiO2 nanocomposite samples with different silicon dioxide (SiO2) filler loading are prepared. The preparation of the samples was carried out based on the solution casting technique. The loading concentrations of SiO2 in the investigating samples are 0, 1, 2.5, 5 and 7.5 wt%. The breakdown strength of the prepared PVC/SiO2 nanocomposite samples is evaluated before and after the thermal ageing test. The evaluation of breakdown strength is carried out based on American Society for Testing and Materials (ASTM) standard. Also, dielectric spectroscopy, which includes dielectric constant (έ) and tangent loss (tan δ) of nanocomposite, is performed before and after the thermal ageing test. Also, the mass losses during thermal ageing of all samples are evaluated. The results show that the breakdown strength, tan δ, and the dielectric constant (έ) of pure PVC and PVC/SiO2 nanocomposites are significantly affected by the thermal ageing test. Adding a small amount of SiO2 nanoparticles to PVC leads to improvement in its dielectric properties before and after the thermal ageing process as compared to the pure PVC. The mass loss of PVC/SiO2 nanocomposite during thermal ageing is less than that of pure PVC and confirms the obtained result from breakdown strength.
Evaluation of an Online Educational Intervention to Increase Knowledge and Self-efficacy in Disaster Responders and Critical Care Transporters Caring for Individuals with Developmental Disabilities
Authors: Edinger Zachariah S. , Powers Kelly A. , Jordan Kathleen S. , Callaway David W. 
Published: January 2019

ABSTRACTObjectiveDisability-related education is essential for disaster responders and critical care transporters to ensure positive patient outcomes. This pilot study evaluated the effect of an online educational intervention on disaster responders and critical care transporters’ knowledge of and feelings of self-efficacy about caring for individuals with developmental disabilities.MethodsA 1-group, pretest-posttest, quasi-experimental design was used. A convenience sample of 33 disaster responders and critical care transporters participated.ResultsOf the 33 participants, only 24% had received prior education on this topic, and 88% stated that such education would be beneficial to their care of patients. Nineteen participants completed both the pretest and posttest, and overall performance on knowledge items improved from 66% correct to 81% correct. Self-efficacy for caring for developmentally disabled individuals improved, with all 10 items showing a statistically significant improvement.ConclusionOnline education is recommended to improve the knowledge and self-efficacy of disaster responders and critical care transporters who care for this vulnerable population after disasters and emergencies. (Disaster Med Public Health Preparedness. 2019;13:677–681)
Faunal remains from recent excavations at Shishan Marsh 1 (SM1), a Late Lower Paleolithic open-air site in the Azraq Basin, Jordan
Authors: Pokines James T. , Lister Adrian M. , Ames Christopher J. H. , Nowell April , Cordova Carlos E. 
Published: January 2019

AbstractExcavations from 2013 to 2015 at the site of Shishan Marsh 1 (SM1) in the Azraq Basin of eastern Jordan have yielded substantial late middle Pleistocene lithic assemblages in association with faunal remains. Faunal preservation is poor, but multiple taxa have been identified, including cf.Panthera leo,Gazellasp.,Boscf.primigenius,Camelussp.,Equusspp., cf.Stephanorhinus hemitoechus,Palaeoloxodoncf.recki, andElephascf.hysudricus. The overall Azraq habitat may have been most similar to a savanna ecosystem, with a mixture of open grassland/shrub habitats and more closed vegetation along the wetlands margins. These taxa were drawn to the relatively lush oasis environment, where they were a dietary resource of the hominin groups exploiting the wetlands resources.
Hawaiian Music and Oceanizing American Studies
Authors: KURAGANO LEAH 
Published: January 2019

American studies has been dedicated to understanding cultural forms from its beginnings as a field. Music, as one such form, is especially centered in the field as a lens through which to seek the cultural “essence” of US America – as texts from which to glean insight into negotiations of intellectual thought, social relations, subaltern resistance, or identity formation, or as a form of labor that produces an exchangeable commodity. In particular, the featuring of folk, indigenous, and popular music directly responded to anxieties in the intellectual circles of the postwar era around America's purported lack of serious culture in comparison to Europe. According to John Gilkeson, American studies scholars in the 1950s and 1960s “vulgarized” the culture concept introduced by the Boasian school of anthropology, opening the door to serious consideration of popular culture as equal in value to high culture.1
OP08 Using Real World Data To Support National Postmarketing Surveillance
Authors: Zuo Yeqin , Mullen Bernie , Hayhurst Rachel , Kaye Karen , Granger Renee , Dartnell Jonathan 
Published: January 2019

Introduction:While medicines and medical tests are developed in a controlled clinical trial environment, postmarketing surveillance in the real world can be challenging. MedicineInsight—a database of longitudinal patient-level clinical information from primary care practices in Australia—is a novel program that collects primary care data to improve postmarketing surveillance at a national level.Methods:MedicineInsight collects de-identified clinical information from primary care practice information systems using data extraction tools. MedicineInsight currently includes 3.6 million regular patients of 3,300 family physicians (general practitioners) from 650 primary care practices across Australia. MedicineInsight data include longitudinal clinical information on diagnosis and medicines (dose, strength, route of administration, medication switches over time, adverse events, and allergies), and pathology testing data. A series of observational studies was developed for postmarketing surveillance of management of a range of health priorities including type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), depression, and antibiotics use.Results:Forty-four percent of patients with T2DM in the MedicineInsight database did not have a recorded hemoglobin A1c result and thirty-one percent did not have a recorded blood pressure reading in the previous 6 months. While guidelines recommend a stepwise approach to the initiation of COPD therapy, forty-nine percent of patients with COPD (with or without asthma) were prescribed dual therapy at initiation and a small number (4.5 percent) were prescribed triple therapy. Between 2011 and 2015, the annual rate of antidepressant prescribing per 1,000 family physician encounters increased by eight percent. High volumes of antibiotics were prescribed for respiratory tract infections in Australian primary care, notwithstanding guideline recommendations that antibiotics are not recommended in most cases.Conclusions:Large scale, real-world clinical data from primary care practices can play an important role in postmarketing surveillance at a national level.
OP12 2017 Health Technology Assessment International Asia Policy Forum: The Importance Of Universal Health Care
Authors: Rintoul Andrew , Trowman Rebecca 
Published: January 2019

Introduction:The fifth Health Technology Assessment International (HTAi) Asia Policy Forum (APF) was held in Beijing, November 2017. The topic of the meeting was ‘Universal Health Care in the Asia Region: Overcoming the Barriers using HTA and Real World Data’. This presentation will focus on the goal of achieving universal health care (UHC) in the Asia region, and specifically the perspective of the World Health Organization (WHO).Methods:The 2017 HTAi APF had senior representatives from HTA agencies, academia, industry active in the region plus representatives from the WHO Geneva office and the Western Pacific Regional Office. A keynote presentation was delivered by the WHO representative and there were guided breakout group discussions.Results:UHC is a key component of the overall aims and objectives of the WHO; universal access to safe, effective, quality and affordable medicines and vaccines for all is at the heart of this. Pharmaceutical spending varies widely across the Asia region and all countries in the region share common problems in attaining UHC. These include inadequate financing, inefficiencies in procurement and supply chain management, limited use of effective pricing policies and negotiations, substandard quality of medicines and widespread inappropriate prescribing and use.Conclusions:HTA can be used to help countries in the Asia region to achieve UHC; it is a tool to support good decision making and hence can help promote more efficient allocation of limited resources. Affordability, however, needs to be at the center of any decision to invest or disinvest, and incremental cost effectiveness ratios should not be used as the sole basis for decision making.
OP19 Are Compassionate Use Programmes Good Predictors of Clinical Benefit?
Authors: Mills Mackenzie 
Published: January 2019

Introduction:In cases of high unmet clinical need, patients can access drugs prior to marketing authorization (MA) and Health Technology Assessment (HTA) through compassionate use programmes (CUP) or special access pathways (SAP). In theory, accelerated access is beneficial for patients with few therapeutic alternatives. In practice, it remains unclear if early access products actually deliver meaningful clinical benefit.Methods:Seventy-five drug-indication pairs were identified that have proceeded through a CUP or SAP in one or more countries including Canada, Australia, France, Sweden, England, and Scotland. Data was collected from regulatory and HTA websites on length of CUP or SAP, time prior to MA, time prior to HTA decision, time between MA and HTA decision, French Transparency Commission added clinical benefit (ASMR), and HTA decision. Cohen kappa scores were calculated in order to assess inter-agency agreement.Results:Across the 75 drug-indication pairs, average time between CUP and marketing authorization was 243 days, and average time between MA and HTA decision was 252 days. No products were deemed to be of major added clinical benefit (ASMR I), only 2.7 percent of products had important added clinical benefit (ASMR II), 26.7 percent of products had moderate added clinical benefit (ASMR III), 40.0 percent of products had minor added clinical benefit (ASMR IV), and 22.7 percent of products had no added clinical benefit (ASMR V). There is little inter-agency agreement in HTA recommendations for products that have proceeded through a CUP. The highest amount of agreement was seen between Canada and Scotland (k = 0.24).Conclusions:Preliminary results suggest that CUP and SAP products accelerate access, but often only provide only moderate or minor improvements in clinical benefit. Further, there is very little agreement across HTA agencies on the value of these products.