bluuebunny/crossref_metadata_2025 huggingface dataset:
Photon Yield Enhancement of Red Fluorophores at Cryogenic Temperatures
Authors: Hulleman Christiaan N. , Li Weixing , Gregor Ingo , Rieger Bernd , Enderlein Jörg
Published: April 2018

Single Molecule Localization Microscopy has become one of the most successful and widely applied methods of Super‐resolution Fluorescence Microscopy. Its achievable resolution strongly depends on the number of detectable photons from a single molecule until photobleaching. By cooling a sample from room temperature down to liquid nitrogen temperatures, the photostability of dyes can be enhanced by more than 100 fold, which results in an improvement in localization precision greater than 10 times. Here, we investigate a variety of fluorescent dyes in the red spectral region, and we find an average photon yield between 3.5 ⋅ 106 to 11 ⋅ 106 photons before bleaching at liquid nitrogen temperatures, corresponding to a theoretical localization precision around 0.1 nm.
Leukocyte Isolation from Brain, Spinal Cord, and Meninges for Flow Cytometric Analysis
Authors: Manglani Monica , Gossa Selamawit , McGavern Dorian B.
Published: April 2018

A continual dialogue exists between the central nervous system (CNS) and immune system that contributes to neural homeostasis as well as protection from microbes, repair following damage, autoimmune disease, and neurodegeneration. Characterization of resident and peripherally derived leukocyte populations within the central nervous system can provide valuable information regarding how these cells contribute to steady‐state and inflammatory conditions. Flow cytometry provides a method to conduct detailed multi‐parameter analyses of immune cells isolated from various tissues. This protocol provides a method to isolate leukocytes from brain, spinal cord, and meninges for flow cytometric analysis and provides a basic framework for phenotyping these cells. © 2018 by John Wiley & Sons, Inc.
The Use of the Fluidigm C1 for RNA Expression Analyses of Single Cells
Authors: DeLaughter Daniel M.
Published: April 2018

Understanding the transcriptional heterogeneity that occurs on the level of a single cell is critical to understanding the gene‐regulatory mechanisms underlying development and disease. Population‐level whole‐transcriptome profiling approaches average gene expression across thousands to millions of cells and are unable to delineate the transcriptional signature of individual cells. Considerable biological heterogeneity between individual cells arises from differences in cell lineage, environment, or response to stimulus. The development of single‐cell RNA sequencing (RNA‐seq) enabled a high‐resolution and unbiased analysis of cell transcriptomes. This unit describes a procedure utilizing an automated microfluidic platform, the Fluidigm C1 system, to simultaneously isolate dozens of single cells in a size‐ and shape‐dependent manner. The microfluidic platform processes cells in individual nanoliter‐scale reactions to convert their contents into double‐stranded cDNA. This cDNA is used to make dual‐indexed libraries using the Illumina Nextera XT library preparation kit for eventual RNA‐seq analysis. © 2018 by John Wiley & Sons, Inc.
Using Barcoded HIV Ensembles (B‐HIVE) for Single Provirus Transcriptomics
Authors: Chen Heng‐Chang , Zorita Eduard , Filion Guillaume J.
Published: April 2018

The latent HIV reservoir is the main barrier to curing AIDS, because infected cells escape the immune system and antiretroviral therapies. Developing new treatment strategies requires technologies to trace latent proviruses. Here, we describe a genome‐wide technique called Barcoded HIV Ensembles (B‐HIVE) to measure HIV expression at the single provirus level. The principle of B‐HIVE is to tag the genome of HIV with DNA barcodes to trace viral transcripts produced by single proviruses in an infected cell population. This in turn reveals which proviruses are active and which are latent or expressed at low level. B‐HIVE is a high‐throughput method to identify and quantify thousands of individual viral transcripts per round of infection. It can be applied in different conditions, characterizing the response of single proviruses to different treatments. Overall, B‐HIVE gives unprecedented insight into the expression of single proviruses in populations of HIV‐infected cells. © 2018 by John Wiley & Sons, Inc.
Engage deaf students in the community
Authors: Hope Joan
Published: April 2018

At the SouthWest Collegiate Institute for the Deaf of Howard College in Texas, students pursue an associate degree in an environment designed for their needs. Danny Campbell, dean of instruction and co‐administrative dean; and Nancy Bonura, dean of student services, co‐administrative dean, and district ADA officer, discussed strategies to support deaf and hard of hearing students.
Review annual compendium for statistics about Americans with disabilities
Authors: Gachichio Ian
Published: April 2018

If you're looking for data to support campus proposals and initiatives, the 2017 Disability Statistics Annual Report and the 2017 Annual Disability Statistics Compendium could provide you with the statistics you need. Produced by the Rehabilitation Research and Training Center on Disability Statistics and Demographics, the compendium pools disability statistics published by various federal agencies.
The effect of tea consumption on the steroid profile
Authors: Coll Sergi , Matabosch Xavier , Garrostas Lorena , Monfort Nuria , Perez‐Maña Clara , Pizarro Nieves , Mateus Julián A. , Ezzel Mohammed , de la Torre Rafael , Ventura Rosa
Published: April 2018

Green tea (GT), along with its flavonol epigallocatechin−3‐gallate (EGCG), has shown to inhibit the UGT2B17 isoenzyme, which is highly involved in the glucuronidation of testosterone (T) and its metabolites. Since the steroid profile (SP) is composed of urinary concentrations of T and related metabolites excreted in both the free and the glucuronide fractions, GT consumption could alter the SP, leading to misunderstanding in doping controls. The aim of the present work was to study the effect of GT consumption on the SP. This study was performed with 29 male volunteers, which could be classified in 2 arms depending on their T/E values (0.12 ± 0.02, n = 12; 1.64 ± 0.90, n = 17). The clinical protocol was designed to evaluate the effect of GT administration on the SP biomarkers. Participants were asked to consume GT with a high content of EGCG for 7 days (5 GT beverages along the whole day for days 1–6 and 9 GT beverages on day 7, corresponding to 520 and 936 mg/day of EGCG, respectively). Urine samples were collected before and during GT consumption at different time periods. The SP was measured using gas chromatography–mass spectrometry. The excretion rates of the SP metabolites did not change after GT consumption. Moreover, the individual evaluation of the subject's steroidal biological passport resulted in normal sequences. The results obtained show that GT consumption does not distort the establishment of normal ranges of SP parameters. Therefore, GT consumption does not need to be considered a confounding factor in the SP evaluation.
Ecological niche modeling re‐examined: A case study with the Darwin's fox
Authors: Escobar Luis E. , Qiao Huijie , Cabello Javier , Peterson A. Townsend
Published: April 2018

Many previous studies have attempted to assess ecological niche modeling performance using receiver operating characteristic (ROC) approaches, even though diverse problems with this metric have been pointed out in the literature. We explored different evaluation metrics based on independent testing data using the Darwin's Fox (Lycalopex fulvipes) as a detailed case in point. Six ecological niche models (ENMs; generalized linear models, boosted regression trees, Maxent, GARP, multivariable kernel density estimation, and NicheA) were explored and tested using six evaluation metrics (partial ROC, Akaike information criterion, omission rate, cumulative binomial probability), including two novel metrics to quantify model extrapolation versus interpolation (E‐space index I) and extent of extrapolation versus Jaccard similarity (E‐space index II). Different ENMs showed diverse and mixed performance, depending on the evaluation metric used. Because ENMs performed differently according to the evaluation metric employed, model selection should be based on the data available, assumptions necessary, and the particular research question. The typical ROC AUC evaluation approach should be discontinued when only presence data are available, and evaluations in environmental dimensions should be adopted as part of the toolkit of ENM researchers. Our results suggest that selecting Maxent ENM based solely on previous reports of its performance is a questionable practice. Instead, model comparisons, including diverse algorithms and parameterizations, should be the sine qua non for every study using ecological niche modeling. ENM evaluations should be developed using metrics that assess desired model characteristics instead of single measurement of fit between model and data. The metrics proposed herein that assess model performance in environmental space (i.e., E‐space indices I and II) may complement current methods for ENM evaluation.
Organometallic–Organic Hybrid Polymers Assembled from Pentaphosphaferrocene, Bipyridyl Linkers, and CuI Ions
Authors: Moussa Mehdi Elsayed , Welsch Stefan , Lochner Matthias , Peresypkina Eugenia V. , Virovets Alexander V. , Scheer Manfred
Published: April 2018

A multicomponent approach of the Pn ligand complex [Cp*Fe(η5‐P5)] (1: Cp* = η5‐C5Me5) with the ditopic organic linkers 4,4′‐bipyridine (2) or trans‐1,2‐di(pyridine‐4‐yl)ethene (3) in the presence of CuI salts of the anions [BF4]– and [PF6]– or the coordinating anion Br–, leads to the formation of four novel organometallic–organic hybrid polymers: the cationic 1D polymeric compounds [Cu4{Cp*Fe(µ3,η5:1:1‐P5)}2(µ,η1:1‐C10H8N2)4(CH3CN)4]n[BF4]4n (4) and [Cu4{Cp*Fe(µ3,η5:1:1‐P5)}2(µ,η1:1‐C10H8N2)4(CH3CN)4]n[PF6]4n (5) as well as the unique neutral threefold 2D → 2D interpenetrated networks [Cu2Cl2{Cp*Fe(µ3,η5:1:1‐P5)}(µ,η1:1‐C12H10N2)]n (6) and [Cu2Br2{Cp*Fe(µ3,η5:1:1‐P5)}(µ,η1:1‐C10H8N2)]n (7).
Mechanistic Understanding towards the Role of Cyclohexene in Enhancing the Efficiency of Manganese Porphyrin‐Catalyzed Aerobic Oxidation of Diphenylmethane
Authors: Jiang Jun , Wang Jie‐Xiang , Zhou Xian‐Tai , Chen Hong‐Yu , Ji Hong‐Bing
Published: April 2018

The selective aerobic oxidation of nonactivated C–H bonds is a key challenge in both industrial and academic research. The catalytic activity of manganese porphyrins (MnTPPCl) towards the aerobic oxidation of diphenylmethane (DPM) is investigated. Compared with the oxidation‐catalyzed MnTPPCl alone, the conversion of DPM is enhanced ca. 6 times (from 7.0 % to 42.5 %) in the presence of cyclohexene. Some in situ characterizations, such as in situ EPR (electron paramagnetic resonance) spectroscopy and in situ UV/Vis spectroscopy are used to investigate the role of cyclohexene in catalytic oxidation. Mechanistic studies suggest that both high‐valent manganese species and cyclohexenyl alkoxyl radicals are favorable for the formation of the carbon radicals. The enhanced activity is related to the easier generation of secondary carbon radicals, triggered by high‐valent manganese species and cyclohexenyl alkoxyl radicals.
Hydroboration, Cyanosilylation, and Sequential Cyanosilylation and Hydroboration of Carbonyl Compounds in the Presence of a TiIV Amido Complex as an Efficient Catalyst
Authors: Harinath Adimulam , Bhattcharjee Jayeeta , Gorantla Koteswar Rao , Mallik Bhabani S. , Panda Tarun K.
Published: April 2018

Catalytic hydroboration and cyanosilylation of a wide range of aldehydes and ketones, with pinacolborane (4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane) and trimethylsilyl cyanide, respectively, in the presence of titanium(IV) complexes [κ2‐{(C5H4N)CH2N‐P(=Se)Ph2}Ti(NMe2)3] (1) and [{κ2‐(C6H4F)NP(=Se)Ph2}Ti(NMe2)3] (2) are reported. The catalytic hydroboration and cyanosilylation processes are high‐yielding and general, and result in efficient conversion of carbonyl compounds into the corresponding products under mild conditions. Titanium catalyst 1 exhibits high tolerance toward several functional groups. First‐order kinetics with respect to the catalyst and each of the substrates were observed for the titanium‐catalyzed hydroboration of carbonyl compounds. First‐principles calculations were performed to explore the catalytic hydroboration reaction mechanism. In addition, a combination of both reactions and sequential cyanosilylation/hydroboration is reported. TiIV complexes 1 and 2 were prepared by aminolysis of [Ti(NMe2)4] with protic ligands [(C5H4N)CH2NHP(=Se)Ph2] (L1H) and [(C6H4F)NHP(=Se)Ph2] (L2H), respectively. The third titanium complex [κ4‐{Ph2P(=Se)NCH(C5H4N)CH(C5H4N)P(=Se)Ph2}‐Ti(NMe2)2] (3) was obtained from the reaction between [Ti(NMe2)4] and ligand L1H in a 1:2 molar ratio at room temperature. The molecular structures of complexes 1 and 3 in the solid state are reported.
New Directions for Evaluative Thinking
Authors: Vo Anne T. , Archibald Thomas
Published: April 2018

The editors identify and synthesize salient themes on the topic of evaluative thinking that emerged throughout the chapters of this volume. In particular, they address three questions: (1) In what ways has this volume broadened and deepened our collective understanding of evaluative thinking? (2) What new directions of inquiry and action regarding evaluative thinking does this volume orient us toward? and (3) What are the implications of this collection of work for the evaluation field?
Values and Culture in Evaluative Thinking: Insights from Aotearoa New Zealand
Authors: Wehipeihana Nan , McKegg Kate
Published: April 2018

Evaluative thinking as currently discussed in evaluation literature is relatively “culture free” in spite of the well‐known connection between values and culture. This chapter reviews the adequacy of applying dominant ways of knowing to evaluative thinking and reasoning in indigenous contexts. Through a case example, it explores how indigenous knowledge systems might influence our conceptions of evaluative thinking, and discusses the potential for the convergence and coexistence of diverse knowledge paradigms for evaluative thinking to better serve the needs and aspirations of indigenous communities.
Toward a Conceptual Understanding of Evaluative Thinking
Authors: Vo Anne T. , Schreiber Jacob S. , Martin Ashley
Published: April 2018

This chapter offers a retrospective analysis of literature related to evaluative thinking. The study was conducted to improve conceptual understandings of the topic through a systematic review of sources published from 1960 to 2016. Using manual, keyword, and proximity search strategies, the authors identified and thematically coded 220 records to create a conceptual model of evaluative thinking. This conceptual model consists of four key thematic domains (Values, Valuing, Cognition, and Application) that constitute evaluative thinking as reflected in the literature to date. Each is discussed in detail, and the implications of this model for the professionalization of the field and practice of evaluation are considered.
Identification of flavour and fragrance constituents
Authors: Bicchi Carlo , Chaintreau Alain , Joulain Daniel
Published: April 2018

The present recommendations describe the criteria required for a publication in Flavour and Fragrance Journal to identify the volatile and non‐volatile constituents of flavours, fragrances, extracts, and essential oils. Notably, the journal has adopted the ‘Statement on the identification in nature of flavouring substances’ made by the International Organization of the Flavor Industry (IOFI).
Collisions in shape memory alloys
Authors: Frémond Michel , Marino Michele , Rocca Elisabetta
Published: April 2018

We present here a model for instantaneous collisions in a solid made of shape memory alloys (SMA) by means of a predictive theory which is based on the introduction not only of macroscopic velocities and temperature, but also of microscopic velocities responsible of the austenite‐martensites phase changes. Assuming time discontinuities for velocities, volume fractions and temperature, and applying the principles of thermodynamics for non‐smooth evolutions together with constitutive laws typical of SMA, we end up with a system of nonlinearly coupled elliptic equations for which we prove an existence and uniqueness result in the 2 and 3 D cases. Finally, we also present numerical results for a SMA 2D solid subject to an external percussion by a hammer stroke.
Formal and informal inter‐organizational coordination: How nurses adapt in complex pathways
Authors: Doessing Anne
Published: April 2018

With the coordination of health care services becoming increasingly complex, the challenges of fragmentation cannot be solved by administrative restructuring alone. Attention must also be given to the coordination practices of professional groups, and, in this respect, the nursing profession is a particularly interesting case. Based on a qualitative case study of Danish nurses in hospital, municipality, and general practice, this article addresses the following question: How does the nursing profession practice formal and informal inter‐organisational coordination in complex pathways, and what is the interplay between the 2 types of coordination? The findings contribute to our knowledge of coordination at the operative level of health care by identifying specific informal practices in inter‐organisational coordination and by showing how informal coordination is activated to support formal coordination in a concurrent organisational and professional ambition of integration. The nurses studied here proved very loyal to formal inter‐organisational coordination mechanisms, prioritising them as first choices of action. When formal procedures were found insufficient, however, the nurses temporarily switched to informal coordination. This was triggered by random encounters with fragmentation, a strong professional engagement in making things work in the interest of the patient, and a constant striving to be on top of things. Informal inter‐organisational coordination is broken down into supplementary and by‐passing practices, and 4 specific by‐passing practices are identified. The discussion offers insight into how a lack of agency related to formal inter‐organisational coordination can be related to negotiated settlements, and informal coordination is considered in terms of “rule bending” within complex systems.
Describing and evaluating healthcare priority setting practices at the county level in Kenya
Authors: Waithaka Dennis , Tsofa Benjamin , Kabia Evelyn , Barasa Edwine
Published: April 2018

Background

Healthcare priority setting research has focused at the macro (national) and micro (patient level), while there is a dearth of literature on meso‐level (subnational/regional) priority setting practices. In this study, we aimed to describe and evaluate healthcare priority setting practices at the county level in Kenya.

Methods

We used a qualitative case study approach to examine the planning and budgeting processes in 2 counties in Kenya. We collected the data through in‐depth interviews of senior managers, middle‐level managers, frontline managers, and health partners (n = 23) and document reviews. We analyzed the data using a framework approach.

Findings

The planning and budgeting processes in both counties were characterized by misalignment and the dominance of informal considerations in decision making. When evaluated against consequential conditions, efficiency and equity considerations were not incorporated in the planning and budgeting processes. Stakeholders were more satisfied and understood the planning process compared with the budgeting process. There was a lack of shifting of priorities and unsatisfactory implementation of decisions. Against procedural conditions, the planning process was more inclusive and transparent and stakeholders were more empowered compared with the budgeting process. There was ineffective use of data, lack of provisions for appeal and revisions, and limited mechanisms for incorporating community values in the planning and budgeting.

Conclusion

County governments can improve the planning and budgeting processes by aligning them, implementing a systematic priority setting process with explicit resource allocation criteria, and adhering to both consequential and procedural aspects of an ideal priority setting process.
HR systems, HR departments, and perceived establishment labor productivity
Authors: Chadwick Clint , Li Pingshu
Published: April 2018

This study examines how an HR department moderates the effects of high‐performance work systems (HPWSs) on perceived establishment performance. Using a representative sample of 125 small and medium‐sized establishments from the 2002 National Organizations Survey, our results indicate a positive interaction between HPWSs and the existence of an establishment HR department with respect to perceived establishment labor productivity. Implications for future strategic HRM research are discussed.
Prenatal diethylstilbestrol exposure and mammographic density
Authors: Strohsnitter William C. , Bertrand Kimberly A. , Troisi Rebecca , Scott Christopher G. , Cheville Andrea L. , Hoover Robert N. , Palmer Julie R. , Vachon Celine M.
Published: April 2018

In a prospective cohort study of the health effects associated with prenatal Diethylstilbestrol (DES) exposure, DES was associated with an increased breast cancer risk after 40 years of age. It is unknown whether it is associated with greater mammographic density, which strongly predicts breast cancer risk. A cohort of DES‐exposed and unexposed women was assembled at the Mayo Clinic in 1975, and followed through 2012 as part of the National Cancer Institute's DES follow‐up study. Mammographic density from 3,637 mammograms for 332 (222 DES‐exposed, 110 unexposed) women in this cohort screened at the Mayo Clinic, Rochester between 1996 and 2015 was determined clinically using the Breast Imaging Reporting and Data System (BI‐RADS). Any effect of prenatal DES exposure on mammographic density was estimated using repeated measures logistic regression. There was no association between prenatal DES exposure and high mammographic density for either premenopausal [Odds ratios (OR) = 0.92 (95% Confidence Interval (CI): 0.50, 1.7] or postmenopausal women (OR = 0.90; 95% CI: 0.54, 1.5). Among premenopausal women, associations differed by body mass index (BMI), with ORs of 1.47 (0.70, 3.1) for women with BMI above the median and 0.53 (0.23, 1.3) for those with BMI below the median (pinteraction = 0.05). Overall, however, prenatal DES exposure was not associated with high mammographic density in this sample of DES Study participants. Consequently, this study does not provide evidence that high mammographic density is involved with the influence of DES on breast cancer risk.
Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients
Authors: Böck Julia , Appenzeller Silke , Haertle Larissa , Schneider Tamara , Gehrig Andrea , Schröder Jörg , Rost Simone , Wolf Beat , Bartram Claus R. , Sutter Christian , Haaf Thomas
Published: April 2018

To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2‐mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age‐matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%). With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%), there was no significant difference between patients and controls. One of 36 HR BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent with a disease‐causing epimutation. Approximately one third (15 of 44) EO BC patients exhibited increased rates of single CpG methylation errors in multiple TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS genes. We propose that epigenetic abnormalities in normal body cells are indicative of disturbed mechanisms for maintaining low methylation and appropriate expression levels and may be associated with an increased BC risk.
Global burden of cutaneous melanoma attributable to ultraviolet radiation in 2012
Authors: Arnold Melina , de Vries Esther , Whiteman David C. , Jemal Ahmedin , Bray Freddie , Parkin Donald Maxwell , Soerjomataram Isabelle
Published: April 2018

Ultraviolet radiation (UVR) is a strong and ubiquitous risk factor for cutaneous melanoma, emitted naturally by the sun but also artificial sources. To shed light on the potential impact of interventions seeking to reduce exposure to UVR in both high and low risk populations, we quantified the number of cutaneous melanomas attributable to UVR worldwide. Population attributable fractions and numbers of new melanoma cases in adults due to ambient UVR were calculated by age and sex for 153 countries by comparing the current melanoma burden with historical data, i.e., the melanoma burden observed in a population with minimal exposure to UVR. Secondary analyses were performed using contemporary melanoma incidence rates in dark‐skinned African populations with low UVR susceptibility as reference. Globally, an estimated 168,000 new melanoma cases were attributable to excess UVR in 2012, corresponding to 75.7% of all new melanoma cases and 1.2% of all new cancer cases. This burden was concentrated in very highly developed countries with 149,000 attributable cases and was most pronounced in Oceania, where 96% of all melanomas (representing 9.3% of the total cancer burden) were attributable to excess UVR. There would be approximately 151,000 fewer melanoma cases worldwide were incidence rates in every population equivalent to those observed in selected low‐risk (dark‐skinned, heavily pigmented) reference populations. These findings underline the need for public health action, an increasing awareness of melanoma and its risk factors, and the need to promote changes in behavior that decrease sun exposure at all ages.
Proton pump inhibitor use and cancer mortality
Authors: Tvingsholm Siri A. , Dehlendorff Christian , Østerlind Kell , Friis Søren , Jäättelä Marja
Published: April 2018

Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer‐specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36,066) compared with nonusers (<2 prescriptions, n = 311,853) or users of histamine H2‐receptor antagonists (H2RA; n = 5,152). Adjusted HRs for cancer‐specific mortality among postdiagnostic PPI users as compared with nonusers or H2RA users were 1.29 (95% CI, 1.27–1.32) and 1.15 (95% CI, 1.10–1.20), respectively. HRs for cancer mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20–1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81–1.04). The associations were stronger among new PPI users after cancer diagnosis, indicating potential confounding. To test the effect of PPIs on tumor growth in a model system free for confounding factors, we investigated the effect of pantoprazole on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth (p = 0.033) and reduced the antitumor activity of gemcitabine (p = 0.008) in fibrosarcoma‐bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In breast carcinoma‐bearing FVB/N mice, pantoprazole had no effect on tumor growth alone but it reduced the life‐prolonging effect of doxorubicin significantly (p = 0.007). Taken together, these data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients.
Strategy on a Page: An ArchiMate‐based tool for visualizing and designing strategy
Authors: Aldea Adina , Iacob Maria‐Eugenia , van Hillegersberg Jos , Quartel Dick , Franken Henry
Published: April 2018

Nowadays, organizations need to be able to adjust more rapidly to the circumstances of their environment, at a strategic, tactical, and operational level. However, most software tools are designed to support the tactical and operational levels, while at a strategic level there are not many options available. In this paper, we propose a software tool which supports modelling of strategic information, covering several well‐known strategy techniques, and also facilitates the design of highly customizable management dashboards. To validate our proposed software tools, we perform two case studies, with two inherently different organizations, namely a public university and an investment fund.
Centering the How: What Teacher Candidates’ Means of Mediation Can Tell Us About Engaging Adolescent Writers
Authors: Barnes Meghan E.
Published: April 2018

Prospective teachers often draw on their own experiences with writing as they envision and plan for future writing instruction. Rather than analyzing the types and topics of writing that teacher candidates engaged in as K–16 students, this study inquired into the mediational means shaping their writing processes. The teacher candidates in this study partnered with local high school students to blog about their varied in‐ and out‐of‐school experiences with writing. An analysis of these blogs revealed that three overarching mediational means—rules, time, and purpose—had either restrictive or enabling effects on participants’ writing. Findings from this study suggest that the value students attach to writing is a function of the mediational means that shape the experience. This study suggests that as literacy teachers prepare for writing instruction, they should pay particular attention to the restrictive and enabling effects of the various mediational means employed.
Evaluation of long‐term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study
Authors: Erbaş Oytun , Erdoğan Mümin Alper , Khalilnezhad Asghar , Solmaz Volkan , Gürkan Fulya Tuzcu , Yiğittürk Gürkan , Eroglu Hüseyin Avni , Taskiran Dilek
Published: April 2018

The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty‐four adult male Sprague–Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1–CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long‐term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.
A facile PCR‐RFLP method for genotyping of ITPA rs1127354 and rs7270101 polymorphisms
Authors: Alavian Seyed Ehsan , Sharafi Heidar , Shirmast Paniz , Alavian Seyed Moayed , Behnava Bita , Pouryasin Mohammad , Keshvari Maryam , Pouryasin Ali
Published: April 2018

Background

Inosine triphosphate pyrophosphatase (ITPA) gene single nucleotide polymorphisms (SNPs), rs1127354 and rs7270101, may cause a functional impairment in ITPase enzyme, resulting anemia protection in patients with chronic hepatitis C virus (HCV) infection undergoing ribavirin (RBV)‐dependent regimens. The main purpose of this study was to provide and validate a simple, rapid, and inexpensive polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) technique for genotyping of ITPA rs1127354 and rs7270101 polymorphisms in chronic HCV‐infected patients.

Methods

In the current study, 100 Iranian patients with chronic hepatitis C were examined and genotyped for ITPA rs1127354 and rs7270101 gene polymorphisms. To genotype rs1127354 and rs7270101 polymorphisms, PCR‐RFLP technique and sequencing technique were performed on these samples. To validate the PCR‐RFLP method, the PCR‐RFLP genotyping results should be 100% concordant with the PCR‐sequencing results.

Results

The rs1127354 and rs7270101 polymorphisms of ITPA gene were genotyped by PCR‐RFLP technique and sequencing simultaneously, and the results of both techniques were 100% concordant in all 100 patients. Both PCR‐RFLP and sequencing techniques indicated that the genotypic frequency of rs7270101 was 80% AA, 19% AC and 1% CC, and for rs1127354 was 79% CC, 20% CA and 1% AA, respectively.

Conclusion

We developed and validated a rapid and inexpensive PCR‐RFLP technique for the detection of ITPA rs1127354 and rs7270101 gene polymorphisms.
Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre‐clinical assessment
Authors: Barbarino Marcella , Cesari Daniele , Intruglio Riccardo , Indovina Paola , Namagerdi Asadoor , Bertolino Franca Maria , Bottaro Maria , Rahmani Delaram , Bellan Cristiana , Giordano Antonio
Published: April 2018

Malignant mesothelioma (MM) is a very aggressive asbestos‐related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti‐helminthic drug pyrvinium pamoate has attracted a strong interest for its anti‐cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β‐catenin pathway and given the important role of this pathway in MM, we investigated the potential anti‐tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down‐regulates the expression of β‐catenin and Wnt‐regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.
Role of geranylgeranylacetone as non‐toxic HSP70 inducer in liver surgery: clinical application
Authors: Tashiro Seiki , Miyake Hidenori , Rokutan Kazuhito
Published: April 2018

Heat shock proteins (HSPs) are rapidly synthesized into cells in response to various types of physical or chemical insults and induce potent resistance to the stressors. A stress‐inducible HSP70 is not expressed in normal conditions, but once HSP70 is excessively induced under various environmental stresses, HSP70‐expressing cells can survive even under lethal conditions. In this review, we focused on the potential role of HSPs particularly HSP70 in liver surgery. A non‐toxic HSP70 inducer, geranylgeranylacetone (GGA), has been introduced to exert a potent cytoprotective action against liver injury after ischemia/reperfusion, massive hepatectomy and liver transplantation in animal experiments. We have tried to explain possible therapeutic benefits of GGA in liver surgery. However, any dependable clinical application has not been done. One of the reasons is that any randomized clinical trial has not being carried out in clinical cases. Therefore, we have advocated the national scale randomized clinical trial for dependable clinical application of GGA.
Green Synthesis of 1,2,4,5‐Tetrasubstituted and 2,4,5‐Trisubstituted Imidazole Derivatives Involving One‐pot Multicomponent Reaction
Authors: Bansal Ravi , Soni Pradeep K. , Halve Anand K.
Published: April 2018

Sodium lauryl sulfate has been found convenient, versatile, and eco‐friendly catalyst for the synthesis of 1,2,4,5‐tetrasubstituted and 2,4,5‐trisubstituted imidazole derivatives by one‐pot multicomponent reactions at 80°C using water as solvent. This protocol afforded advantages, that is, the metal‐free reaction, purification of products by non‐chromatographic method, and excellent yields.
Electrochemical monitoring of malondialdehyde biomarker in biological samples via electropolymerized amino acid/chitosan nanocomposite
Authors: Hasanzadeh Mohammad , Mokhtari Fozieh , Jouyban‐Gharamaleki Vahid , Mokhtarzadeh Ahad , Shadjou Nasrin
Published: April 2018

This study reports on the electropolymerization of a low toxic and biocompatible nanopolymer with entitle poly arginine‐graphene quantum dots‐chitosan (PARG‐GQDs‐CS) as a novel strategy for surface modification of glassy carbon surface and preparation of a new interface for measurement of malondialdehyde (MDA) in exhaled breath condensate. Electrochemical deposition, as a well‐controlled synthesis procedure, has been used for subsequently layer‐by‐layer preparation of GQDs‐CS nanostructures on a PARG prepolymerized on the surface of glassy carbon electrode using cyclic voltammetry techniques in the regime of −1.5 to 2 V. The modified electrode appeared as an effective electroactivity for detection of MDA by using cyclic voltammetry, linear sweep voltammetry, and differential pulse voltammetry. The prepared modified electrode demonstrated a noticeably good activity for electrooxidation of MDA than PARG. Enhancement of peak currents is ascribed to the fast heterogeneous electron transfer kinetics that arise from the synergistic coupling between the excellent properties of PARG and semiconducting polymer, GQDs as high density of edge plane sites and subtle electronic characteristics and unique properties of CS such as excellent film‐forming ability, high permeability, good adhesion, nontoxicity, cheapness, and a susceptibility to chemical modification. The prepared sensor showed 1 oxidation processes for MDA at potentials about 1 V with a low limit of quantification 5.94 nM. Finally, application of new sensor for determination of MDA in exhaled breath condensate was suited. In general, the simultaneous attachment of GQDs and CS to structure of poly amino acids provides new opportunities within the personal healthcare.
Total choline quantification measured by 1H MR spectroscopy as early predictor of response after neoadjuvant treatment for locally advanced breast cancer: The impact of immunohistochemical status
Authors: Drisis Stylianos , Flamen Patrick , Ignatiadis Michael , Metens Thierry , Chao Shih‐Li , Chintinne Marie , Lemort Marc
Published: April 2018

Background

Validation of new biomarkers is essential for the early evaluation of neoadjuvant treatments.

Purpose

To determine whether measurements of total choline (tCho) by 1H spectroscopy could predict morphological or pathological complete response (pCR) of neoadjuvant treatment and whether breast cancer subgroups are related to prediction accuracy.

Study Type

Prospective, nonrandomized, monocentric, diagnostic study.

Population

Sixty patients were initially included with 39 women participating in the final cohort.

Field Strength/Sequence

A 1.5T scanner was used for acquisition and MRS was performed using the syngo GRACE sequence.

Assessment

MRS and MRI examinations were performed at baseline (TP1), 24–72 hours after first chemotherapy (TP2), after the end of anthracycline treatment (TP3), and MRI only after the end of taxane treatment (TP4). Early (EMR) and late (LMR) morphological response were defined as %ΔDmax13 or %ΔDmax14, respectively. Responders were patients with %ΔDmax >30. Pathological complete response (pCR) patients achieved a residual cancer burden score of 0.

Statistical Tests

T‐test, receiver operating characteristic (ROC) curves, multiple regression, logistic regression, one‐way analysis of variance (ANOVA) analysis were used for the analysis.

Results

At TP1 there was a significant difference between response groups for tCho1 concerning EMR prediction (P = 0.05) and pCR (P < 0.05) and for Kep1 (P = 0.03) concerning LMR prediction. At TP2, no modification of tCho and other parameters could predict response. At TP3, ΔtCho, ΔDmax, and ΔVol could predict LMR (P < 0.05 for all parameters), pCR (P < 0.05 for all parameters), and ΔKtrans could predict only pCR (P = 0.04). Logistic regression at baseline showed the highest area under the curve (AUC) of 0.9 for prediction of pCR. The triple negative (TN) subgroup showed significantly higher tCho at baseline (P = 0.02) and higher ΔtCho levels at TP3 (P < 0.05).

Data Conclusion

Baseline measurements of tCho in combination with clinicopathological criteria could predict non‐pCR with a high AUC. Furthermore, tCho quantification for prediction of pCR was more sensitive for TN tumors.

Level of Evidence: 1

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2018;48:982–993.
Computer‐aided diagnosis of prostate cancer using a deep convolutional neural network from multiparametric MRI
Authors: Song Yang , Zhang Yu‐Dong , Yan Xu , Liu Hui , Zhou Minxiong , Hu Bingwen , Yang Guang
Published: April 2018

Background

Deep learning is the most promising methodology for automatic computer‐aided diagnosis of prostate cancer (PCa) with multiparametric MRI (mp‐MRI).

Purpose

To develop an automatic approach based on deep convolutional neural network (DCNN) to classify PCa and noncancerous tissues (NC) with mp‐MRI.

Study Type

Retrospective.

Subjects

In all, 195 patients with localized PCa were collected from a PROSTATEx database. In total, 159/17/19 patients with 444/48/55 observations (215/23/23 PCas and 229/25/32 NCs) were randomly selected for training/validation/testing, respectively.

Sequence

T2‐weighted, diffusion‐weighted, and apparent diffusion coefficient images.

Assessment

A radiologist manually labeled the regions of interest of PCas and NCs and estimated the Prostate Imaging Reporting and Data System (PI‐RADS) scores for each region. Inspired by VGG‐Net, we designed a patch‐based DCNN model to distinguish between PCa and NCs based on a combination of mp‐MRI data. Additionally, an enhanced prediction method was used to improve the prediction accuracy. The performance of DCNN prediction was tested using a receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Moreover, the predicted result was compared with the PI‐RADS score to evaluate its clinical value using decision curve analysis.

Statistical Test

Two‐sided Wilcoxon signed‐rank test with statistical significance set at 0.05.

Results

The DCNN produced excellent diagnostic performance in distinguishing between PCa and NC for testing datasets with an AUC of 0.944 (95% confidence interval: 0.876–0.994), sensitivity of 87.0%, specificity of 90.6%, PPV of 87.0%, and NPV of 90.6%. The decision curve analysis revealed that the joint model of PI‐RADS and DCNN provided additional net benefits compared with the DCNN model and the PI‐RADS scheme.

Data Conclusion

The proposed DCNN‐based model with enhanced prediction yielded high performance in statistical analysis, suggesting that DCNN could be used in computer‐aided diagnosis (CAD) for PCa classification.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:1570–1577
Nonsustained ventricular tachycardia does not affect the prognosis of neuromuscular diseases: A preliminary and retrospective study
Authors: Kamihara Takahiro , Yasuma Fumihiko , Murohara Toyoaki
Published: April 2018

Background

Nonsustained ventricular tachycardia (NSVT) is sometimes observed in patients with neuromuscular diseases (NMDs). The aim of this study was to assess the role of NSVT in the survival prognosis of NMD patients.

Methods

We retrospectively analyzed the patients with NMDs who had undergone Holter ECG recordings at a single center between February and August 2012. Sixty‐eight patients were enrolled in this study. The 5 year follow‐up was assessed according to the cumulative event‐free rate.

Results

Twenty‐one patients died during the follow‐up, seven of whom died by cardiac death. The Kaplan–Meier survival curve that compared the patients with NSVT and those without NSVT indicated the NSVT was not related to the rate of all causes of death or cardiac death in those patients with NMDs. The survival curve was not significantly changed after the adjustment by age and ejection fraction.

Conclusion

No significant correlations between NSVT and the prognosis in patients with NMDs were found.
Glu571 of PheT plays a pivotal role in the thermal stability of Escherichia coli PheRS enzyme
Authors: Ashwin Sri Bala Sridar , Madhumathi Irulappan , Vinodha Sengottuvel , Munavar M Hussain
Published: April 2018

As of date the two temperature sensitive mutations isolated in pheST operon include pheS5 (G293→A293) and pheT354. Recently, we reported that G673 of pheS defines a hot spot for intragenic suppressors of pheS5. In this investigation, in 13 independent experiments, a collection of temperature sensitive mutants were isolated by localized mutagenesis. Complementation using clones bearing pheS+, pheT+, and pheS+T+ indicated that 34 mutants could harbor lesion(s) in pheS and four could be in pheT and one mutant might be a double mutant. Surprisingly, all the 34 pheS mutants harbored the very same (G293→A293) transition mutation as present in the classical pheS5 mutant. Most unexpectedly, the four pheT mutants isolated harbored the same G1711→A1711 transition, a mutation which is hitherto unreported. Since all the four pheT mutants were defined by the same G1711→A1711 base change, we believe that getting other mutations could be hard hitting and therefore it is proposed that G1711 itself could be a “hot spot” for emergence of Ts mutations in pheT and similarly G293 itself could be a “hot spot” for Ts lesions in pheS. These results clearly imply a vital role for Glutamic acid571 (Glu571) of PheT and reinforce criticality of Glycine98 (Gly98) of PheS in the thermal stability of PheRS enzyme.