bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family physician perceptions of the role and value of the clinical pharmacist in the management of patients with type 2 diabetes
Authors: Harmes Kathryn M. , Shih Elizabeth , Plegue Melissa , Shultz Cameron , Diez Heidi L. 
Published: April 2019

AbstractPurposeClinical pharmacists can help primary care physicians (PCPs) manage medications for patients with poorly controlled type 2 diabetes. Studies have shown that clinical pharmacist involvement in care can improve outcomes such as glycosylated hemoglobin (A1C), blood pressure and lipid control, and decrease episodes of hypoglycemia. Despite these findings, some PCPs may be slow or disinclined to refer to clinical pharmacists when available. This study addressed PCP perceptions regarding referral to clinical pharmacists and endocrinologists for patients with poorly controlled type 2 diabetes.MethodsPhysicians from five family medicine sites were surveyed. Physicians were queried regarding their patterns for patient referral to endocrinologists and/or clinical pharmacists. Clinical contributions and importance of factors to consider when referring were compared between clinical pharmacists and endocrinologists using paired t tests.ResultsFifty physicians responded to the survey, resulting in a response rate of 73.5%. The majority of PCPs indicated that they have referred to endocrinologists (89.5%) and clinical pharmacists (93.5%) for specialty care. PCPs tended to refer to clinical pharmacists sooner and at lower A1C values than to endocrinologists. PCPs also considered multiple medical comorbidities, history of noncompliance with medical recommendations, low reading ability or math skills, complex psychosocial situations, fear of needles, or difficulty affording medications or supplies to be more important when referring patients to clinical pharmacists than endocrinologists.ConclusionWe hypothesized that referrals to a clinical pharmacist or endocrinologist are made with careful consideration of the patients' needs. PCPs reported increased utilization of clinical pharmacists for patients with nonmedical needs, indicating that extra time, education, and psychosocial support provided by the clinical pharmacist is highly valued.
A novel screening method for transition metal‐based anticancer compounds using zebrafish embryo‐larval assay and inductively coupled plasma‐mass spectrometry analysis
Authors: Karas Brittany F. , Côrte‐Real Leonor , Doherty Cathleen L. , Valente Andreia , Cooper Keith R. , Buckley Brian T. 
Published: April 2019

AbstractAs novel metallodrugs continue to emerge, they are evaluated using models, including zebrafish, that offer unique sublethal endpoints. Testing metal‐based anticancer compounds with high‐throughput zebrafish toxicological assays requires analytical methods with the sensitivity to detect these sublethal tissue doses in very small sample masses (e.g., egg mass 100 μg). A robust bioanalytical model, zebrafish embryos coupled with inductively coupled plasma‐mass spectrometry (ICPMS) for measurement of delivered dose, creates a very effective means for screening metal‐based chemotherapeutic agents. In this study, we used ICPMS quantitation with the zebrafish embryo assays to detect metal equivalents at multiple response endpoints for two compounds, the chemotherapeutic agent cisplatin and ruthenium (Ru)‐based prospective metallodrug, PMC79. We hypothesized that cisplatin and PMC79 have different mechanisms for inducing apoptosis and result in similar lesions but different potencies following water‐borne exposure. An ICPMS method was developed to detect the metal in waterborne solution and tissue (detection limit: 5 parts per trillion for Ru or platinum [Pt]). The Ru‐based compound was more potent (LC50: 7.8 μm) than cisplatin (LC50: 158 μm) and induced disparate lesions. Lethality from cisplatin exposure exhibited a threshold (values >15 mg/L) while no threshold was observed for delayed hatching (lowest observed adverse effect level 3.75 mg/L cisplatin; 8.7 Pt (ng)/organism). The Ru organometallic did not have a threshold for lethality. Cisplatin‐induced delayed hatching was investigated further by larval‐Pt distribution and preferentially distributed to the chorion. We propose that zebrafish embryo‐larval assays coupled with ICPMS serve as a powerful platform to evaluate relative potency and toxic effects of metallodrug candidates.
Metabolic control by dehydroascorbic acid: Questions and controversies in cancer cells
Authors: Ferrada Luciano , Salazar Katterine , Nualart Francisco 
Published: April 2019

AbstractFor a long time, the effect of vitamin C on cancer cells has been a controversial concept. From Linus Pauling's studies in 1976, it was proposed that ascorbic acid (AA) could selectively kill tumor cells. However, further research suggested that vitamin C has no effect on tumor survival. In the last decade, new and emerging functions for vitamin C have been discovered using the reduced form, AA, and the oxidized form, dehydroascorbic acid (DHA), independently. In this review, we summarized the latest findings related to the effects of DHA on the survival and metabolism of tumor cells. At the same time, we put special emphasis on the bystander effect and the recycling capacity of vitamin C in various cellular models, and how these concepts can affect the experimentation with vitamin C and its therapeutic application in the treatment against cancer.
A Phase 1 Mass Balance Study of 14C‐Labeled Talazoparib in Patients With Advanced Solid Tumors
Authors: Yu Yanke , Chung Chin‐Hee , Plotka Anna , Quinn Kevin , Shi Haihong , Pápai Zsuzsanna , Nguyen Linh , Wang Diane 
Published: April 2019

AbstractThis paper describes the pharmacokinetics (PK), mass balance, metabolic profiling, and safety of talazoparib after a single oral dose of 14C‐talazoparib in 6 patients with advanced solid tumors. Patients were aged ≥18 years, with a histologically confirmed advanced solid tumor at screening. A single 1‐mg dose of talazoparib oral solution supplemented with 100 µCi of 14C‐labeled talazoparib was administered. Blood, urine, and feces samples were collected at various time points and analyzed for talazoparib and 14C radioactivity. Metabolic profiling and identification were also carried out. Mean recovery of 14C radioactivity was 68.7% in urine and 19.7% in feces. Talazoparib was minimally metabolized. Renal excretion of unchanged talazoparib was a major route of elimination, with mean recovery of 54.6% of the administered dose, whereas fecal excretion of talazoparib was limited, with mean recovery of 13.6% of the administered dose. No major metabolites of talazoparib were identified in plasma, and no metabolites that individually represented more than 10% of the administered dose were recovered in urine or feces. The concentration‐time profiles of unchanged talazoparib, total 14C radioactivity in plasma, and total 14C radioactivity in whole blood were similar, with a median time at peak concentrations of 30 minutes and mean half‐life of 89.8, 96.2, and 77.6 hours, respectively. Talazoparib was minimally metabolized, and renal excretion of unchanged talazoparib was the major route of elimination.
Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan
Authors: Li I‐Hsun , Shih Jui‐Hu , Tsai Chien‐Sung , Chien Wu‐Chien , Kao Hui‐Han , Pan Ke‐Ting , Cheng Yih‐Dih , Kao Li‐Ting 
Published: April 2019

AbstractThis large‐scale case‐control study in Taiwan elucidated the potential connection between fibrate use and liver cancer by using the Longitudinal Health Insurance Database 2005 with a propensity‐score–matching design. In total, 4173 patients diagnosed as having liver cancer were included as cases, and 4173 propensity‐score–matched patients without liver cancer were identified as controls. The association between previous fibrate use and liver cancer occurrence was demonstrated using conditional logistic regression. Fibrate use was noted in 371 (8.89%) cases and 481 (11.53%) controls. After adjustments, the cases had significantly lower odds of previous fibrate use than did the controls (adjusted odds ratio 0.70, 95%CI 0.60‐0.82); moreover, regardless of the patients’ sex, age group, and comorbidities, the cases were less likely to have used fibrates than were the controls. Dose‐dependent analysis revealed that 1‐695 cumulative defined daily doses of fibrates may significantly induce a protective effect for liver cancer. Although other fibrate dose intervals did not reach statistical significance, the dose‐response curve presented the trend of a protective effect for liver cancer among the fibrate users. In summary, fibrate use had a significant protective effect against liver cancer in this Asian population.
Understanding the present and preparing for the future: Exploring the needs of diagnostic and elective genomic medicine patients
Authors: East Kelly M. , Cochran Meagan , Kelley Whitley V. , Greve Veronica , Emmerson Kristina , Raines Grace , Cochran Jesse Nicholas , Hott Adam M. , Bick David 
Published: April 2019

AbstractAdvances in genomic knowledge and technology have increased the use of comprehensive clinical sequencing tests. Genome sequencing has established utility for diagnosing patients with rare, undiagnosed diseases as well as interest in an elective context, without a clinical indication for testing. The Smith Family Clinic for Genomic Medicine, LLC in Huntsville, AL is a private practice genomic medicine clinic caring for both diagnostic (79%) and elective (21%) patients. Diagnostic and elective patients are seen on a clinical basis and receive standard care. Genome sequencing is provided on a self‐pay basis, with assistance available for diagnostic patients who have financial need. Here, we describe demographics and motivations of the distinct patient populations and our experiences engaging patients in online education. Diagnostic patients were motivated by the possibility of receiving an explanation for symptoms (96%) while elective patients were motivated by the chance to learn about future disease risk (57%). Elective patients were less likely to engage with online education, with only 28% reading all assigned topics compared to 54% of diagnostic patients. Understanding the needs, interests, and barriers unique to diagnostic and elective patients is critical to inform individualized and scalable best practices in patient education and engagement.
Thermodynamics‐based modelling of gas chromatography separations across column geometries and systems, including the prediction of peak widths
Authors: Stevenson Keisean A. J. M. , Harynuk James J. 
Published: April 2019

AbstractThermodynamics‐based models have been demonstrated to be useful for predicting retention time and peak widths in gas chromatography and two‐dimensional gas chromatography separations. However, the collection of data to train the models can be time consuming, which lessens the practical utility of the method. In this contribution, a method for obtaining thermodynamic‐based data to predict peak widths in temperature‐programmed gas chromatography is presented. Experimental work to collect data for peak width prediction is identical to that required to collect data for retention time prediction using approaches that we have presented previously. Using this combined approach, chromatograms including retention times and peak widths are predicted with very high accuracy. Typical errors in retention time are < 0.5%, while errors in peak width are typically < 5% as demonstrated using polycycic aromatic hydrocarbons and a mixture containing compounds with aldehyde, ketone, alkene, alkane, alcohol, and ester functionalities.
Spatial variation in the biochemical and isotopic composition of corals during bleaching and recovery
Authors: Wall Christopher B. , Ritson‐Williams Raphael , Popp Brian N. , Gates Ruth D. 
Published: April 2019

AbstractOcean warming and the increased prevalence of coral bleaching events threaten coral reefs. However, the biology of corals during and following bleaching events under field conditions is poorly understood. We examined bleaching and postbleaching recovery in Montipora capitata and Porites compressa corals that either bleached or did not bleach during a 2014 bleaching event at three reef locations in Kāne‘ohe Bay, O‘ahu, Hawai‘i. We measured changes in chlorophylls, tissue biomass, and nutritional plasticity using stable isotopes (δ13C, δ15N). Coral traits showed significant variation among periods, sites, bleaching conditions, and their interactions. Bleached colonies of both species had lower chlorophyll and total biomass, and while M. capitata chlorophyll and biomass recovered 3 months later, P. compressa chlorophyll recovery was location dependent and total biomass of previously bleached colonies remained low. Biomass energy reserves were not affected by bleaching, instead M. capitata proteins and P. compressa biomass energy and lipids declined over time and P. compressa lipids were site specific during bleaching recovery. Stable isotope analyses did not indicate increased heterotrophic nutrition in bleached colonies of either species, during or after thermal stress. Instead, mass balance calculations revealed that variations in δ13C values reflect biomass compositional change (i.e., protein : lipid : carbohydrate ratios). Observed δ15N values reflected spatiotemporal variability in nitrogen sources in both species and bleaching effects on symbiont nitrogen demand in P. compressa. These results highlight the dynamic responses of corals to natural bleaching and recovery and identify the need to consider the influence of biomass composition in the interpretation of isotopic values in corals.
Direct Fabrication of Nanodomes‐Combined Surface Relief Gratings on Azobenzene Polymer Films with Controlled Shapes and Sizes
Authors: Kim Kang‐Han , Lee Yong Min , Ryou Myung‐Hyun , Jeong Yong‐Cheol 
Published: April 2019

ABSTRACTIn this study, we present nanodomes‐combined surface relief gratings (SRGs) of azopolymer films with controlled shapes and sizes. We investigate the effect of the polarization mode of light interference on leading nanodomes in the conventional SRG patterns. In addition, we also systematically study the relationship between Bragg distance of light interference and shapes of nanodomes. From this, we explain the anisotropic self‐assembled behavior nanodomes in photoaddressable azopolymer films regarding polarization modes as well as spatial confinement effect. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 731–737
Performance of anti‐Müllerian hormone (AMH) levels measured by Beckman Coulter Access AMH assay to predict oocyte yield following controlled ovarian stimulation for in vitro fertilization
Authors: Asada Yoshimasa , Tsuiki Miyako , Sonohara Megumi , Fukunaga Noritaka , Hattori Yukio , Inoue Daichi , Ito Rie , Hashiba Yoshiki 
Published: April 2019

AbstractPurposeWe evaluated the performance of anti‐Müllerian hormone (AMH) measured by the Beckman Coulter fully automated Access assay to predict oocyte yield following controlled ovarian stimulation (COS) for in vitro fertilization (IVF).MethodsThe correlation between the Access assay and the pre‐mixing method with Generation II ELISA assay (Gen II pre‐mix assay) was assessed using 230 blood samples. The relationship of AMH level measured by the Access assay and the actual number of oocytes retrieved following COS was assessed using 3296 IVF cycles. The performances of AMH, follicle stimulating hormone (FSH), and estradiol (E2) in predicting the responses to COS were also evaluated by constructing receiver operating characteristic (ROC) curves.ResultsThe AMH levels measured just before oocyte retrieval by the Access assay and the number of oocytes retrieved following COS showed a good correlation with R = 0.655. The ROC analysis revealed that the sensitivity of AMH was comparable with or lower than that of E2 but higher than that of FSH.ConclusionsWith the improved Access AMH assays, AMH was as sensitive as E2 and could become an accurate marker of ovarian response to COS in more than 3000 Japanese IVF patients.
Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation
Authors: Chahal Jaskarndip , Gómez-Aristizábal Alejandro , Shestopaloff Konstantin , Bhatt Shashank , Chaboureau Amélie , Fazio Antonietta , Chisholm Jolene , Weston Amanda , Chiovitti Julia , Keating Armand , Kapoor Mohit , Ogilvie-Harris Darrell J. , Syed Khalid A. , Gandhi Rajiv , Mahomed Nizar N. , Marshall Kenneth W. , Sussman Marshall S. , Naraghi Ali M. , Viswanathan Sowmya 
Published: April 2019

Abstract
Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM-MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient-reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast-enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM-MSCs were characterized by a panel of anti-inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro-inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM-MSC anti-inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM-MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM-MSC dosing and BM-MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746–757
Cryo‐EM‐On‐a‐Chip: Custom‐Designed Substrates for the 3D Analysis of Macromolecules
Authors: Alden Nick A. , Varano A. Cameron , Dearnaley William J. , Solares Maria J. , Luqiu William Y. , Liang Yanping , Sheng Zhi , McDonald Sarah M. , Damiano John , McConnell Jennifer , Dukes Madeline J. , Kelly Deborah F. 
Published: April 2019

AbstractThe fight against human disease requires a multidisciplinary scientific approach. Applying tools from seemingly unrelated areas, such as materials science and molecular biology, researchers can overcome long‐standing challenges to improve knowledge of molecular pathologies. Here, custom‐designed substrates composed of silicon nitride (SiN) are used to study the 3D attributes of tumor suppressor proteins that function in DNA repair events. New on‐chip preparation strategies enable the isolation of native protein complexes from human cancer cells. Combined techniques of cryo‐electron microscopy (EM) and molecular modeling reveal a new modified form of the p53 tumor suppressor present in aggressive glioblastoma multiforme cancer cells. Taken together, the findings provide a radical new design for cryo‐EM substrates to evaluate the structures of disease‐related macromolecules.
Chemical Confinement and Utility of Lithium Polysulfides in Lithium Sulfur Batteries
Authors: Tang Tianyu , Hou Yanglong 
Published: April 2019

AbstractLithium sulfur (Li–S) batteries featuring abundant resources and cost‐efficiency are regarded as a promising next‐generation energy storage system with high theoretical capacity and energy density. However, several drawbacks impede the development of Li–S batteries, especially the shuttle effects of soluble lithium polysulfides (LiPS) which lead to severe capacity decay and short cycling lifespan. Though the existence of LiPS can result in performance decline and battery failure, the management of the LiPS should be balanced. This review focuses on both sides of the LiPS. One is the confinement of LiPS by chemical interactions between novel cathode hosts with LiPS, another is the utility of the LiPS in Li–S batteries with stable performance. Ultimately, the future developments and prospects of Li–S batteries are discussed.
Development and validation of a scientific (formal) reasoning test for college students
Authors: Kalinowski Steven T. , Willoughby Shannon 
Published: April 2019

AbstractWe present a multiple‐choice test, the Montana State University Formal Reasoning Test (FORT), to assess college students' scientific reasoning ability. The test defines scientific reasoning to be equivalent to formal operational reasoning. It contains 20 questions divided evenly among five types of problems: control of variables, hypothesis testing, correlational reasoning, proportional reasoning, and probability. The test development process included the drafting and psychometric analysis of 23 instruments related to formal operational reasoning. These instruments were administered to almost 10,000 students enrolled in introductory science courses at American universities. Questions with high discrimination were identified and assembled into an instrument that was intended to measure the reasoning ability of students across the entire spectrum of abilities in college science courses. We present four types of validity evidence for the FORT. (a) The test has a one‐dimensional psychometric structure consistent with its design. (b) Test scores in an introductory biology course had an empirical reliability of 0.82. (c) Student interviews confirmed responses to the FORT were accurate indications of student thinking. (d) A regression analysis of student learning in an introductory biology course showed that scores on the FORT predicted how well students learned one of the most challenging concepts in biology, natural selection.
Evolutionary journey and characterisation of a novel pan‐gene associated with beer strains of Saccharomyces cerevisiae
Authors: Vakirlis Nikolaos , Monerawela Chandre , McManus Gavin , Ribeiro Orquidea , McLysaght Aoife , James Tharappel , Bond Ursula 
Published: April 2019

AbstractThe sequencing of over a thousand Saccharomyces cerevisiae genomes revealed a complex pangenome. Over one third of the discovered genes are not present in the S. cerevisiae core genome but instead are often restricted to a subset of yeast isolates and thus may be important for adaptation to specific environmental niches. We refer to these genes as “pan‐genes,” being part of the pangenome but not the core genome.Here, we describe the evolutionary journey and characterisation of a novel pan‐gene, originally named hypothetical (HYPO) open‐reading frame. Phylogenetic analysis reveals that HYPO has been predominantly retained in S. cerevisiae strains associated with brewing but has been repeatedly lost in most other fungal species during evolution. There is also evidence that HYPO was horizontally transferred at least once, from S. cerevisiae to Saccharomyces paradoxus. The phylogenetic analysis of HYPO exemplifies the complexity and intricacy of evolutionary trajectories of genes within the S. cerevisiae pangenome.To examine possible functions for Hypo, we overexpressed a HYPO‐GFP fusion protein in both S. cerevisiae and Saccharomyces pastorianus. The protein localised to the plasma membrane where it accumulated initially in distinct foci. Time‐lapse fluorescent imaging revealed that when cells are grown in wort, Hypo‐gfp fluorescence spreads throughout the membrane during cell growth. The overexpression of Hypo‐gfp in S. cerevisiae or S. pastorianus strains did not significantly alter cell growth in medium‐containing glucose, maltose, maltotriose, or wort at different concentrations.