bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Cytotoxic and Melanogenesis‐Inhibitory Activities of Limonoids from the Leaves of Azadirachta indica (Neem).
Authors: Takagi Mio , Tachi Yosuke , Zhang Jie , Shinozaki Takuro , Ishii Kenta , Kikuchi Takashi , Ukiya Motohiko , Banno Norihiro , Tokuda Harukuni , Akihisa Toshihiro
Published: July 2014

isolation, structure elucidation and evaluation of 17 limonoids, including the three novel ones (I), (II), (III), for their cytotoxic activities, their inhibitory activities against melanogenesis in B16 melanoma cells and against the Epstein—Barr virus early antigen
ChemInform Abstract: Tortuosenes A and B, New Diterpenoid Metabolites from the Formosan Soft Coral Sarcophyton tortuosum.
Authors: Lin Kuan‐Hua , Tseng Yen‐Ju , Chen Bo‐Wei , Hwang Tsong‐Long , Chen Hsing‐Yin , Dai Chang‐Feng , Sheu Jyh‐Horng
Published: July 2014

The isolation, structure elucidation and determination of the absolute configuration of the title compounds are described.
ChemInform Abstract: Copper(I) Chloride‐Catalyzed Aerobic Oxidative Arylation of Glycine Ester and Amide Derivatives.
Authors: Huo Congde , Wang Cheng , Wu Mingxia , Jia Xiaodong , Xie Haisheng , Yuan Yong
Published: July 2014

A simple copper(I)‐catalyzed process for the selective aerobic oxidative coupling of N‐arylglycine esters and amides at C‐3 of various indoles.
ChemInform Abstract: (‐)‐(2S,3R,Z)‐Nakinadine A: First Asymmetric Synthesis and Absolute Configuration Assignment.
Authors: Davies Stephen G. , Fletcher Ai M. , Roberts Paul M. , Shah Rushabh S. , Thompson Amber L. , Thomson James E.
Published: July 2014

The key step of the 10‐step synthesis of the marine alkaloid (‐)‐(I) is an asymmetric Mannich‐type reaction.
ChemInform Abstract: Synthesis, Microstructure and Properties of BiFeO3‐Based Multiferroic Materials: A Review
Authors: Bernardo M. S.
Published: July 2014

Review: 168 refs.
ChemInform Abstract: Sequential Catalysis for Stereoselective Synthesis of Complex Polyketides
Authors: Herkommer Daniel , Schmalzbauer Bjoern , Menche Dirk
Published: July 2014

Review: 111 refs.
ChemInform Abstract: Single Electron Transfer in Radical Ion and Radical‐Mediated Organic, Materials and Polymer Synthesis
Authors: Zhang Na , Samanta Shampa R. , Rosen Brad M. , Percec Virgil
Published: July 2014

Review: 1086 refs.
ChemInform Abstract: The Prehistory of Discotic Mesophases — A Personal Account of the Study of the Mesophase of Diisobutylsilane Diol
Authors: Lydon John E.
Published: July 2014

Review: 18 refs.
ChemInform Abstract: Organic Chemistry Collaborative Synthesis
Authors: Wood John L.
Published: July 2014

Review: 6 refs.
ChemInform Abstract: A Brief Discussion on Nucleophilic Substitution Reaction on Saturated Carbon Atom
Authors: Ding Yan
Published: July 2014

Review: 4 refs.
ChemInform Abstract: Carbocatalysis by Graphene‐Based Materials
Authors: Navalon Sergio , Dhakshinamoorthy Amarajothi , Alvaro Mercedes , Garcia Hermenegildo
Published: July 2014

Review: 273 refs.
ChemInform Abstract: The Nematic Phases of Bent‐Core Liquid Crystals
Authors: Gleeson Helen F. , Kaur Sarabjot , Goertz Verena , Belaissaoui Abdel , Cowling Stephen , Goodby John W.
Published: July 2014

Review: 54 refs.
EDF‐based goodness‐of‐fit tests for ranked‐set sampling
Authors: Frey Jesse , Wang Le
Published: July 2014

Parametric statistical procedures based on ranked‐set sampling are sensitive both to departures from the parametric family and to departures from perfect rankings. In this paper, we develop goodness‐of‐fit tests that are sensitive to departures of both types. These tests are modelled on the Kolmogorov–Smirnov and Cramér–von Mises goodness‐of‐fit tests for simple random sampling, and they take advantage of the fact that under perfect rankings, the cumulative distribution functions (CDFs) for the judgment order statistics are deterministic functions of the population CDF. We consider multiple ways of combining information across the judgment strata, and we find that summing or taking the maximum of separate stratum‐by‐stratum test statistics seems to give the best power. We prove that the best of the proposed tests are consistent against all alternatives.The Canadian Journal of Statistics42: 451–469; 2014 © 2014 Statistical Society of Canada
Lifestyle and metabolic syndrome in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study
Authors: Smith Webb A. , Li Chenghong , Nottage Kerri A. , Mulrooney Daniel A. , Armstrong Gregory T. , Lanctot Jennifer Q. , Chemaitilly Wassim , Laver Joseph H. , Srivastava Deo Kumar , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K.
Published: July 2014

BACKGROUND

Childhood cancer survivors (CCS) are at an increased risk of developing metabolic syndrome (MetSyn), which may be reduced with lifestyle modifications. The purpose of this investigation was to characterize lifestyle habits and associations with MetSyn among CCS.

METHODS

CCS who were ≥ 10 years from diagnosis, aged > 18 years, and participating in the St. Jude Lifetime Cohort Study completed medical and laboratory tests and a food frequency questionnaire. The Third Report of the National Cholesterol Education Program Adult Treatment Panel criteria were used to classify participants with MetSyn. Anthropometric, food frequency questionnaire, and self‐reported physical activity data were used to characterize lifestyle habits according to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations. Those who met ≥ 4 of 7 recommendations were classified as having followed guidelines. Sex‐stratified log‐binomial regression models were used to evaluate associations between dietary/lifestyle habits and MetSyn, adjusted for age, age at cancer diagnosis, receipt of cranial radiotherapy, education, and household income.

RESULTS

Among 1598 CCS (49.2% of whom were male, with a median age of 32.7 years [range, 18.9 years‐60.0 years]), 31.8% met criteria for MetSyn and 27.0% followed WCRF/AICR guidelines. Females who did not follow WCRF/AICR guidelines were 2.4 times (95% confidence interval, 1.7‐3.3) and males were 2.2 times (95% confidence interval, 1.6‐3.0) more likely to have MetSyn than those who followed WCRF/AICR guidelines.

CONCLUSIONS

Adherence to a heart‐healthy lifestyle is associated with a lower risk of MetSyn among CCS. There is a need to determine whether lifestyle interventions prevent or remediate MetSyn in CCS. Cancer 2014;120:2742–2750. © 2014 American Cancer Society.
p16INK4a overexpression is not linked to oncogenic human papillomaviruses in patients with high‐grade urothelial cancer cells
Authors: Piaton Eric , Casalegno Jean‐Sébastien , Advenier Anne‐Sophie , Decaussin‐Petrucci Myriam , Mege‐Lechevallier Florence , Ruffion Alain , Mekki Yahia
Published: July 2014

BACKGROUND

p16INK4a Is overexpressed in almost all precancerous and carcinomatous lesions of the uterine cervix, secondary to interference between high‐risk human papillomaviruses (hr‐HPVs) and the retinoblastoma gene product. Overexpression of p16INK4a has also been identified in patients with high‐grade urothelial lesions, both cytologically and histologically. However, the etiological role of HPV has not been documented except in inverted papillomas, low‐grade bladder tumors, and younger patients. We therefore attempted to verify if HPV DNA was detectable in p16INK4a‐positive urothelial tumors.

METHODS

A total of 90 urinary cytology samples (33 negative/low‐grade cases and 57 high‐grade proliferations) were analyzed for p16INK4a and HPV DNA. HPV genotyping was performed by polymerase chain reaction using a low‐density DNA microarray enabling the detection of 35 HPVs. A reasoned approach combining tissue genotyping and in situ hybridization (ISH) for hr‐HPVs was used in patients with urinary HPV.

RESULTS

Low‐risk HPV (HPV‐84) and hr‐HPVs (HPV‐16, ‐31, and ‐70) were detected. The prevalence of hr‐HPVs in the urine was low: 5 of 82 patients (6.1%) and only 4 of 50 patients (8.0%) with high‐grade urothelial malignancy. p16INK4a overexpression was noted in 49 high‐grade samples (85.9%). In patients with p16INK4a‐positive tumor cells and hr‐HPV in the urine, HPV genotyping and ISH for hr‐HPVs were negative in matched tissue sections.

CONCLUSIONS

Our study shows a low prevalence of hr‐HPVs in the urine of patients with high‐grade urothelial malignancy. In those, p16INK4a overexpression occurs in the absence of demonstrable HPV DNA in the tissue sections, contrary to what is noted in gynecopathology. Cancer (Cancer Cytopathol) 2014;122:760–769. © 2014 American Cancer Society.
Lithium–Air Oxygen Shuttle Battery with a ZrO2‐Based Ion‐Conducting Oxide Electrolyte
Authors: Inoishi Atsushi , Matsuka Maki , Sakai Takaaki , Ju Young‐Wan , Ida Shintaro , Ishihara Tatsumi
Published: July 2014

A lithium–air battery based on the concept of an “oxygen shuttle” with a calcium‐stabilized ZrO2 electrolyte is described. The observed open‐circuit voltage and discharge capacity are 1.81 V and 2179 mAh per gram of lithium, respectively, at 1073 K. When considering the transport number of an oxide ion at P in an anode chamber, the observed open‐circuit voltage is reasonable. The internal resistance of the lithium–air battery has been analyzed with complex impedance, and the main internal resistance is anodic overpotential because of the platinum electrode used. After discharge, a much larger diffusion resistance, which may suggest surface oxidation of lithium, is observed. However, the observed anodic overpotential is similar to that in a magnesium–air cell reported previously, and much smaller than that of the H2–air fuel cell.
Au–Co3O4/C as an Efficient Electrocatalyst for the Oxygen Evolution Reaction
Authors: Li Zhuo‐ying , Ye Kai‐hang , Zhong Qi‐sui , Zhang Chan‐juan , Shi Shu‐ting , Xu Chang‐wei
Published: July 2014

Carbon black that is introduced into Co3O4 will reduce the overpotential of the oxygen evolution reaction. By adding Au, the Co3O4/C catalyst exhibits superior electrochemical activity and excellent stability for the oxygen evolution reaction. The catalyst with a weight ratio of Au to Co3O4 of 1:3 gives the best performance. After loading with Au, the binding energy value of Co 2p has a positive shift, which will increase formation of CoIV cations of the active centers.
Higher titers of anti‐Chlamydia pneumoniae IgG in diabetic retinopathy: a cross‐sectional study
Authors: Banaee Touka , Daneshvar Kakhki Ramin , Abrishami Mojtaba , Mahmoudi Mahmoud , Farzadnia Mehdi
Published: July 2014

Background

Chronic inflammation has a role in the pathogenesis of diabetic retinopathy. Infection with intracellular organisms may incite chronic inflammation. This study was conducted to investigate the association between previous infection with Chlamydia pneumoniae (an intracellular microorganism) and diabetic retinopathy.

Methods

Patients with type 2 diabetes mellitus (30–60 years old) and age‐matched normal controls were recruited. Patients with history of cardiovascular or cerebrovascular disease, recent pulmonary infection and the presence of age‐related macular degeneration were excluded from the study. Complete ophthalmic examinations were performed. Fasting blood sugar and haemoglobin levels were measured in diabetic patients and controls, and HgbA1c, blood urea nitrogen, creatinine and 24‐h urine protein were measured in diabetic patients. Anti‐C. pneumoniae IgG (enzyme‐linked immunosorbent assay) was measured in the sera of all participants.

Results

A total of 215 type 2 diabetic patients and 243 normal healthy controls were included. Anti‐C. pneumoniae IgG titers were higher in patients affected by diabetic retinopathy than participants without retinopathy (74.78 ± 33.38 vs 66.18 ± 31.40, p = 0.028). Diabetic patients with diabetic retinopathy also had higher titers than diabetic patients without diabetic retinopathy (74.78 ± 33.38 vs 66.11 ± 33.41, p = 0.042). Of different variables including age, body mass index, haemoglobin level, glycated haemoglobin level, fasting blood sugar, mean arterial pressure and blood urea nitrogen, only age (r = 0.17; p = 0.001) and body mass index (r = 0.15; p = 0.003) were correlated with anti‐C. pneumoniae IgG levels. In regression analysis, the presence of diabetic retinopathy was still a determinant of the antibody level (p = 0.03).

Conclusion

Anti‐C. pneumoniae IgG titers were higher in patients with diabetic retinopathy, which may indicate a role of this infection in the pathogenesis of diabetic retinopathy. Copyright © 2014 John Wiley & Sons, Ltd.
Adolescent TBI‐induced hypopituitarism causes sexual dysfunction in adult male rats
Authors: Greco Tiffany , Hovda David A. , Prins Mayumi L.
Published: July 2014

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI‐induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long‐term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI‐induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 193–202, 2015
Reversed brain size sexual dimorphism accompanies loss of parental care in white sticklebacks
Authors: Samuk Kieran , Iritani Davis , Schluter Dolph
Published: July 2014

Uncovering factors that shape variation in brain morphology remains a major challenge in evolutionary biology. Recently, it has been shown that brain size is positively associated with level of parental care behavior in various taxa. One explanation for this pattern is that the cognitive demands of performing complex parental care may require increased brain size. This idea is known as the parental brain hypothesis (PBH). We set out to test the predictions of this hypothesis in wild populations of threespine stickleback (Gasterosteus aculeatus). These fish are commonly known to exhibit (1) uniparental male care and (2) sexual dimorphism in brain size (males>females). To test thePBH, we took advantage of the existence of closely related populations of stickleback that display variation in parental care behavior: common marine threespine sticklebacks (uniparental male care) and white threespine sticklebacks (no care). To begin, we quantified genetic differentiation among two common populations and three white populations from Nova Scotia. We found overall low differentiation among populations, althoughFSTwas increased in between‐type comparisons. We then measured the brain weights of males and females from all five populations along with two additional common populations from British Columbia. We found that sexual dimorphism in brain size is reversed in white stickleback populations: males have smaller brains than females. Thus, while several alternatives need to be ruled out, thePBHappears to be a reasonable explanation for sexual dimorphism in brain size in threespine sticklebacks.
Historical and recent processes shaping the geographic range of a rocky intertidal gastropod: phylogeography, ecology, and habitat availability
Authors: Fenberg Phillip B. , Posbic Karine , Hellberg Michael E.
Published: July 2014

Factors shaping the geographic range of a species can be identified when phylogeographic patterns are combined with data on contemporary and historical geographic distribution, range‐wide abundance, habitat/food availability, and through comparisons with codistributed taxa. Here, we evaluate range dynamism and phylogeography of the rocky intertidal gastropodMexacanthina lugubris lugubrisacross its geographic range – the Pacific coast of the Baja peninsula and southernCalifornia. We sequenced mitochondrialDNA(CO1) from ten populations and compliment these data with museum records, habitat availability and range‐wide field surveys of the distribution and abundance ofM. l. lugubrisand its primary prey (the barnacleChthamalus fissus). The geographic range ofM. l. lugubriscan be characterized by three different events in its history: an old sundering in the mid‐peninsular region of Baja (~ 417,000 years ago) and more recent northern range expansion and southern range contraction. The mid‐peninsular break is shared with many terrestrial and marine species, althoughM. l. lugubrisrepresents the first mollusc to show it. This common break is often attributed to a hypothesized ancient seaway bisecting the peninsula, but forM. l. lugubrisit may result from large habitat gaps in the southern clade. Northern clade populations, particularly near the historical northern limit (prior to the 1970s), have high local abundances and reside in a region with plentiful food and habitat – which makes its northern range conducive to expansion. The observed southern range contraction may result from the opposite scenario, with little food or habitat nearby. Our study highlights the importance of taking an integrative approach to understanding the processes that shape the geographic range of a species via combining range‐wide phylogeography data with temporal geographic distributions and spatial patterns of habitat/food availability.
Generation Expansion Planning Considering Mass Penetration of Renewable Energy Generation and Supply Reliability
Authors: Manabe Yusuke , Hara Ryoichi , Kita Hiroyuki
Published: July 2014

In the future, renewable energy (RE) generation systems will be constructed and interconnected to the power system by nonutility entities such as generation companies and residential customers. Therefore, generation expansion planning (GEP) should consider the effects of RE generation. The purpose of this paper is to discuss the best GEP from the economic, supply reliability, and environmental aspects considering the penetration of RE generation. For this purpose, this paper proposes a model of a utility's GEP process considering RE generation. The proposed method is based on stochastic dynamic programming (SDP) in which long‐term uncertainties are modeled by geometric Brownian motion (GBM) and the binomial lattice process. The variation of RE generation output due to the weather conditions (short‐term uncertainty) is also considered in the proposed method by means of the net load curve.
High prevalence of iron deficiency in patients with acute decompensated heart failure
Authors: Cohen‐Solal Alain , Damy Thibaud , Terbah Mohamed , Kerebel Sébastien , Baguet Jean‐Philippe , Hanon Olivier , Zannad Faiez , Laperche Thierry , Leclercq Christophe , Concas Victor , Duvillié Ladan , Darné Bernadette , Anker Stefan , Mebazaa Alexandre
Published: July 2014

Aims

Limited data are available on iron parameters in patients hospitalized for decompensation of chronic heart failure.

Methods and results

Iron parameters of patients hospitalized for decompensation of chronic heart failure were prospectively assessed during the 72 h after hospital admission. Iron deficiency was defined according to the 2012 European Society of Cardiology Guidelines. Overall, 411 men (75 ± 12 years; 75% NYHA functional classes III/IV) and 421 women (81 ± 11 years; 71% NYHA classes III/IV) were evaluated. The prevalence of iron deficiency was 69% in men and 75% in women (including 41% and 49% with absolute iron deficiency, respectively). The prevalence of anaemia in men (<13 g/dL) was 68% and in women (<12 g/dL) it was 52%. Among non‐anaemic patients, the prevalence of iron deficiency was 57% in men and 79% in women. Only 9% of patients received iron supplementation at the time of admission (oral, 9%; intravenous, 0.2%). Multivariate analysis showed that anaemia and antiplatelet treatment in men, and diabetes and low C‐reactive protein in women, were independently associated with iron deficiency.

Conclusions

Iron deficiency is very common in patients admitted for acute decompensated heart failure, even among non‐anaemic patients. Given the benefit of iron therapy in chronic heart failure, our results emphasize the need to assess iron status not only in chronic heart failure patients, but even more so in those admitted for worsening heart failure, regardless of gender, heart failure severity, or haemoglobin level. Initiating iron therapy in hospitalized heart failure patients needs to be investigated.
Two‐Step Synthesis of 2‐Aminoindolizines from 2‐Alkylpyridines
Authors: Kucukdisli Murat , Opatz Till
Published: July 2014

An efficient method for the synthesis of 2‐aminoindolizines by the 5‐exo‐dig cyclization of 2‐alkyl‐1‐(1‐cyanoalkyl)pyridinium salts has been developed. These substrates were prepared by N‐alkylation of 2‐alkylpyridines with readily available cyanohydrin triflates. The method allows the introduction of various substituents at the 1‐, 3‐, 6‐, 7‐, and 8‐positions and leaves no undesired acceptor groups in the products.
Analysis of device‐to‐device communications with exclusion regions underlaying 5G networks
Authors: Xu Xiaohui , Wang Haibo , Feng Hao , Xing Chengwen
Published: July 2014

Device‐to‐device (D2D) communication underlaying cellular networks is an effective way to improve spectral efficiency and alleviate the traffic load of base stations, therefore it is considered as one of the key technologies in the fifth generation mobile communications, also referred to as IMT‐2020. However, it also introduces interference between D2D terminals and cellular users. In this work, we adopt both exclusion regions (ERs) and open‐loop fraction power control (OFPC) to mitigate the D2D‐to‐Cellular interference in a multicell uplink spectrum‐sharing scenario. We derive the closed‐form expressions of outage probability (OP) and area spectral efficiency (ASE) using stochastic geometry, and reveal the impact of the D2D user equipment (DUE) density versus cellular user equipment (CUE) density (in other words, how many DUEs can reuse the resource of a CUE per cell), D2D communication distance, different ER sizes, and of the compensation factor in OFPC. Numerical results show that adopting ERs could both decrease the OP of cellular users and increase the network ASE, and a proper ER radius can be selected by network operators according to their target OP, D2D users' density, and the communication distance of D2D users. Copyright © 2014 John Wiley & Sons, Ltd.
Machines that Go ‘Ping’: Medical Technology and Health Expenditures in OECD Countries
Authors: Willemé Peter , Dumont Michel
Published: July 2014

Technology is believed to be a major determinant of increasing health spending. The main difficulty to quantify its effect is to find suitable proxies to measure medical technological innovation. This paper's main contribution is the use of data on approved medical devices and drugs to proxy for medical technology. The effects of these variables on total real per capita health spending are estimated using a panel model for 18 Organisation for Economic Co‐operation and Development (OECD) countries covering the period 1981–2012. The results confirm the substantial cost‐increasing effect of medical technology, which accounts for almost 50% of the explained historical growth of spending. Despite the overall net positive effect of technology, the effect of two subgroups of approvals on expenditure is significantly negative. These subgroups can be thought of as representing ‘incremental medical innovation’, whereas the positive effects are related to radically innovative pharmaceutical products and devices. A separate time series model was estimated for the USA because the FDA approval data in fact only apply to the USA, while they serve as proxies for the other OECD countries. Our empirical model includes an indicator of obesity, and estimations confirm the substantial contribution of this lifestyle variable to health spending growth in the countries studied. Copyright © 2014 John Wiley & Sons, Ltd.
Global distribution and prevalence of hepatitis C virus genotypes
Authors: Messina Jane P. , Humphreys Isla , Flaxman Abraham , Brown Anthony , Cooke Graham S. , Pybus Oliver G. , Barnes Eleanor
Published: July 2014

Hepatitis C virus (HCV) exhibits high genetic diversity, characterized by regional variations in genotype prevalence. This poses a challenge to the improved development of vaccines and pan‐genotypic treatments, which require the consideration of global trends in HCV genotype prevalence. Here we provide the first comprehensive survey of these trends. To approximate national HCV genotype prevalence, studies published between 1989 and 2013 reporting HCV genotypes are reviewed and combined with overall HCV prevalence estimates from the Global Burden of Disease (GBD) project. We also generate regional and global genotype prevalence estimates, inferring data for countries lacking genotype information. We include 1,217 studies in our analysis, representing 117 countries and 90% of the global population. We calculate that HCV genotype 1 is the most prevalent worldwide, comprising 83.4 million cases (46.2% of all HCV cases), approximately one‐third of which are in East Asia. Genotype 3 is the next most prevalent globally (54.3 million, 30.1%); genotypes 2, 4, and 6 are responsible for a total 22.8% of all cases; genotype 5 comprises the remaining <1%. While genotypes 1 and 3 dominate in most countries irrespective of economic status, the largest proportions of genotypes 4 and 5 are in lower‐income countries. Conclusion: Although genotype 1 is most common worldwide, nongenotype 1 HCV cases—which are less well served by advances in vaccine and drug development—still comprise over half of all HCV cases. Relative genotype proportions are needed to inform healthcare models, which must be geographically tailored to specific countries or regions in order to improve access to new treatments. Genotype surveillance data are needed from many countries to improve estimates of unmet need. (Hepatology 2015;61:77–87)
Conjugated bilirubin triggers anemia by inducing erythrocyte death
Authors: Lang Elisabeth , Gatidis Sergios , Freise Noemi F. , Bock Hans , Kubitz Ralf , Lauermann Christian , Orth Hans Martin , Klindt Caroline , Schuier Maximilian , Keitel Verena , Reich Maria , Liu Guilai , Schmidt Sebastian , Xu Haifeng C. , Qadri Syed M. , Herebian Diran , Pandyra Aleksandra A. , Mayatepek Ertan , Gulbins Erich , Lang Florian , Häussinger Dieter , Lang Karl S. , Föller Michael , Lang Philipp A.
Published: July 2014

Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver‐damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284)
Computational Studies of Smell and Taste Receptors
Authors: Di Pizio Antonella , Niv Masha Y.
Published: July 2014

Smell and taste are among the basic senses with which we perceive the world around us. In addition to enabling recognition of chemical moieties that provide social or nutritional clues, taste and smell receptors are expressed in many extraoral tissues, including the gastrointestinal, respiratory, and reproductive systems. It is, therefore, likely that taste and smell receptors have additional physiological roles, which are currently under intensive study. Most of the taste modalities, as well as olfaction, are mediated by G‐protein coupled receptors (GPCRs). Recent breakthroughs in crystallography and signaling studies of GPCRs (celebrated by the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka) provide excellent opportunities for applying this information towards furthering our understanding of taste and smell signaling. No crystal structures of odorant or taste receptors are currently available. However, computational techniques, many of which stem from the pioneering contributions of the 2013 Nobel Prize in Chemistry laureates, Martin Karplus, Michael Levitt, and Arieh Warshel, can shed light on the function of taste and olfactory GPCRs. In this review, we highlight examples of iterative combinations of simulation and experiment that were successfully applied toward delineating binding modes of tastants and odorants and toward predicting additional ligands. Further studies are required in order to answer remaining questions regarding receptor promiscuity versus selectivity, the details of receptor coupling to G‐proteins, and the roles of oligomerization and of allosteric modulation in taste and smell transduction.
Using Critical Interpretive Lenses to Examine Glass Ceiling Effects Through Qualitative Research
Authors: Patton Lori D. , Haynes Chayla M.
Published: July 2014

This chapter highlights the importance of qualitative approaches to studying the glass ceiling in contrast to exclusively quantitative measures.
Factors affecting the computation of the 13C shielding in disaccharides
Authors: Garay Pablo G. , Martin Osvaldo A. , Scheraga Harold A. , Vila Jorge A.
Published: July 2014

Knowledge of the three‐dimensional structures of glycans and glycoproteins is useful for a full understanding of molecular processes in which glycans are involved, such as antigen‐recognition and virus infection, to name a few. Among the ubiquitous nuclei in glycan molecules, the 13C nucleus is an attractive candidate for computation of theoretical chemical shifts at the quantum chemical level of theory to validate and determine glycan structures. For this purpose, it is important to determine, first, which carbons can be used as probes to sense conformational changes and, second, all factors that affect the computation of the shielding, at the density functional theory (DFT) level of theory, of those carbons. To answer such questions, we performed a series of analyses on low‐energy conformations, obtained by sampling the glycosidic torsional angles (ϕ, ψ) every 10°, of 12 disaccharides. Our results provide evidence that: (i) the carbons that participate in the glycosidic linkage are the most sensitive probes with which to sense conformational changes of disaccharides; (ii) the rotation of the hydroxyl groups closest to the glycosidic linkage significantly affects the computation of the shieldings of the carbons that participate in the glycosidic linkage; (iii) it is not possible to obtain the shieldings of one disaccharide from the computed values of a different disaccharide or from those disaccharides that differ in the anomeric state; and (iv) a proper basis set distribution, a functional, and a step size, with which to sample the conformational space, are necessary to compute shieldings accurately and rapidly. © 2014 Wiley Periodicals, Inc.
Microwave‐Assisted Catalyst Free Three Component Synthesis of Mono and Bis Spiro Pyrazolopyridines in Solvent Free Reaction
Authors: Nikpassand Mohammad , Zare Fekri Leila , Jamshidi Neda
Published: July 2014

Multicomponent synthesis of mono and bis‐spiro pyrazolopyridines from isatin derivatives, indanedione, and 3‐methyl‐5‐aminopyrazole under microwave irradiation in the absence of any catalyst or solvent with high yield and short reaction time is reported.
Patient safety: This is public health
Authors: Card Alan J.
Published: July 2014

Avoidable patient harm is a major public health concern, and may already have surpassed heart disease as the leading cause of death in the United States. While the public health community has contributed much to one aspect of patient harm prevention, infection control, the tools and techniques of public health have far more to offer to the emerging field of patient safety science. Patient safety practice has become increasingly professionalized in recent years, but specialist degree programs in the field remain scarce. Healthcare organizations should consider graduate training in public health as an avenue for investing in the professional development of patient safety practitioners, and schools and programs of public health should support further research and teaching to support patient safety improvement.
Diagnostic error: Untapped potential for improving patient safety?
Authors: Groszkruger Dan
Published: July 2014

How many diagnostic errors occur? How often do errors cause harm, and how serious is that harm? Do we understand the major causes of diagnostic errors? Really, we don't know how to answer these questions! This article seeks to define a challenge facing all healthcare risk managers, whose usual methods of identifying and analyzing errors have not, and cannot, supply this missing information. What should risk managers do about diagnostic error? Our medical literature acknowledges the existence of a problem, but offers few practical solutions. This article will review some promising theories from the literature regarding how to identify and remediate diagnostic errors, and identify some tools and resources available to risk managers.
A hybrid solid‐fluorous phase radioiodination and purification platform
Authors: Dzandzi James P. K. , Vera Denis R. Beckford , Valliant John F.
Published: July 2014

A new class of fluorous materials was developed to create a hybrid solid‐solution phase strategy for the expedient preparation and HPLC‐free purification of 125I‐labeled compounds. The system is referred to as a hybrid platform in that it combines solution phase labeling and fluorous solid‐phase purification in one step as opposed to two separate individual processes. Treatment of fluorous arylstannanes coated on fluorous silica with [125I]NaI and the appropriate oxidant made it possible to produce and selectively isolate the nonfluorous radiolabeled products in high purity (>98%) free from excess starting material and unreacted radioiodine. Examples included simple aryl and heterocyclic (click) derivatives, known radiopharmaceuticals including meta‐iodobenzylguanidine (MIBG) and iododeoxyuridine (IUdR), and a new agent with high affinity for prostate‐specific membrane antigen. The coated fluorous silica kits are simple to prepare, and reactions can be performed at room temperature using different oxidants generating products in minutes in biocompatible solutions.
Development of kit formulations for 99mTcN‐MPO: a cationic radiotracer for myocardial perfusion imaging
Authors: Zheng Yumin , Ji Shundong , Tomaselli Elena , Liu Shuang
Published: July 2014

The objective of this study was to develop a kit formulation for [99mTcN(mpo)(PNP5)]+ (MPO = 2‐mercaptopyridine oxide), (99mTcN‐MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two‐vial formulation and single‐vial formulations with/without SnCl2) to explore the factors influencing radiochemical purity (RCP) of 99mTcN‐MPO. We found that the most important factor affecting the RCP of 99mTcN‐MPO was the purity of PNP5. 99mTcN‐MPO was prepared >98% RCP (n = 20) using the two‐vial formulation. For single‐vial formulations with/without SnCl2, β‐cyclodextrin (β‐CD) is particularly useful as a stabilizer for PNP5. The RCP of 99mTcN‐MPO was 95–98% using β‐CD, but its RCP was only 90–93% with γ‐cyclodextrin (γ‐CD). It seems that PNP5 fits better into the inner cavity of β‐CD, which forms more stable inclusion complex than γ‐CD in the single‐vial formulations. The results from biodistribution and imaging studies in Sprague–Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon‐emission computed tomography data suggested that high quality images could be obtained at 0–30‐min post‐injection without significant interference from the liver radioactivity. Considering the ease for 99mTc‐labeling and high RCP of 99mTcN‐MPO, the non‐SnCl2 single‐vial formulation is an attractive choice for future clinical studies.
Measurement of renal cortical thickness using noncontrast‐enhanced steady‐state free precession MRI with spatially selective inversion recovery pulse: Association with renal function
Authors: Noda Yasufumi , Ito Katsuyoshi , Kanki Akihiko , Tamada Tsutomu , Yamamoto Akira , Kazuya Yasokawa , Higaki Atsushi
Published: July 2014

Purpose

To assess whether noncontrast‐enhanced steady‐state free precession (SSFP) magnetic resonance imaging (MRI) with a spatially selective inversion recovery (IR) pulse can improve the visibility of renal corticomedullary differentiation in patients showing renal dysfunction, and to investigate the correlation between renal cortical thickness and estimated glomerular filtration rate (eGFR).

Materials and Methods

Sixty‐five patients with and without chronic kidney diseases (CKD) were investigated. Based on eGFR, patients were divided into three groups (Group 1, eGFR < 60; Group 2, eGFR = 60–90; and Group 3, eGFR > 90). All patients underwent noncontrast‐enhanced SSFP MRI with spatially selective IR pulses and minimal renal cortical thickness was measured.

Results

The mean corticomedullary contrast ratio was significantly higher in SSFP images with optimal TI than in in‐phase images in all three groups (P = 0.001). Positive correlation was seen between the corticomedullary contrast ratio in SSFP images with optimal TI and eGFR (P = 0.011, r = 0.314). A significantly positive correlation was observed between minimal renal cortical thickness and eGFR (P < 0.01, r = 0.495).

Conclusion

Noncontrast‐enhanced SSFP MRI with a spatially selective IR pulse using optimal TI can improve the visibility of renal corticomedullary differentiation even in patients with renal insufficiency. The decrease in renal cortical thickness measured using this technique correlated significantly with eGFR. J. Magn. Reson. Imaging 2015;41:1615–1621. © 2014 Wiley Periodicals, Inc.
Temporal effects of vascular endothelial growth factor and 3,5‐cyclic monophosphate on blood–brain barrier solute permeability in vivo
Authors: Shi Lingyan , Zeng Min , Fu Bingmei M.
Published: July 2014

To test the hypothesis that vascular endothelial growth factor (VEGF) can transiently increase the blood–brain barrier permeability, P, as for peripheral microvessels and that the elevation of 3,5‐cyclic monophosphate (cAMP) levels can inhibit the VEGF‐induced acute hyperpermeability, we employed multiphoton microscopy to quantify the cerebral microvessel permeability P to various‐sized solutes under VEGF and cAMP treatments. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a microgrinder. Fluorescein (MW 376Da), fluorescein isothioyanate‐dextran‐20k (FITC‐Dex‐20k), FITC‐Dex‐70k, or Alexa Fluor 488‐IgG in 1% bovine serum albumin mammalian Ringer's solution was injected into the cerebral circulation via the ipsilateral carotid artery with a syringe pump. Simultaneously, temporal images were collected from the brain parenchyma ∼100–200 μm below the pia mater. P was determined from the rate of tissue solute accumulation around individual microvessels. Exposure to 1 nM VEGF transiently increased P to 2.2, 10.5, 9.8, and 12.8 times control values, for fluorescein, Dex‐20k, Dex‐70k, and IgG, respectively, within 30 sec, and all returned to control levels within 2 min. After 20 min of pretreatment with 2 mM of the cAMP analog 8‐bromo‐cAMP, the initial increase by 1 nM VEGF was completely abolished in P of all solutes. The response pattern of P to VEGF and cAMP and the ratios of the peak to control values for rat cerebral microvessels are similar to those for rat mesenteric (peripheral) microvessels, except that the ratios are higher in P of cerebral microvessels for the intermediate and large solutes. These results imply a new approach for delivering large therapeutic agents to the brain. © 2014 Wiley Periodicals, Inc.
A statistical method based on remote sensing for the estimation of air temperature in China
Authors: Chen Fengrui , Liu Yu , Liu Qiang , Qin Fen
Published: July 2014

Environmental applications require accurate air temperature (Tair) datasets with different temporal and spatial resolutions. Existing methods generally improve the estimation accuracy ofTairusing environmental variables as auxiliary data to overcome problems related to sparse metrological stations. However, these data are always fixed and do not comprehensively explain the variations inTairvalues at all temporal and spatial scales. Moreover, these methods seldom consider the spatial heterogeneity of relationships betweenTairand auxiliary data. This heterogeneity is often caused by several factors, such as land type, topography, and climate. This study proposes an estimation method to produce maximum, minimum, and meanTair(Tmax,Tmin, andTmean) datasets at different temporal and spatial resolutions using satellite‐derived digital elevation model data and both nighttime and daytime land surface temperature data as auxiliary data. The method is based on the assumption that the relationships betweenTairand the chosen auxiliary data vary spatially. These relationships were further explored using geographically weighted regression with adaptive bi‐square kernel function. The derived relationships were used to construct aTairestimation model. MonthlyTairdata with 5‐km resolution and 8‐dayTairdata with 1‐km resolution were produced for 2010. The results show that the proposed method can accurately represent the variations inTair; theR2values were in the range of 0.95–0.99 for the monthlyTairdata and 0.93–0.99 for the 8‐dayTairdata. The root mean square errors (RMSEs) for the monthly and 8‐dayTmax,Tmin, andTmeandata of the year 2010 were 1.29 and 1.45 °C, 1.24 and 1.29 °C, and 0.8 and 1.2 °C, respectively. These results were compared with those from other estimation methods, specifically the estimation ofTairbased on multiple linear regression (EATMLR) and regression kriging (EATRK). The proposed method was found to produce RMSEs that were 25–26% smaller than EATMLR and 34–42% smaller than EATRK.
Scapular dyskinesis is detrimental to shoulder tendon properties and joint mechanics in a rat model
Authors: Reuther Katherine E. , Thomas Stephen J. , Tucker Jennica J. , Yannascoli Sarah M. , Caro Adam C. , Vafa Rameen P. , Liu Stephen S. , Gordon Joshua A. , Bhatt Pankti R. , Kuntz Andrew F. , Soslowsky Louis J.
Published: July 2014

Shoulder tendon injuries are frequently seen in the presence of abnormal scapular motion, termed scapular dyskinesis. The cause and effect relationship between scapular dyskinesis and shoulder injury has not been directly defined. We developed and used an animal model to examine the initiation and progression of pathological changes in the rotator cuff and biceps tendon. Sixty male Sprague–Dawley rats were randomized into two groups: nerve transection (to induce scapular dyskinesis, SD) or sham nerve transection (control). The animals were euthanized 4 and 8 weeks after surgery. Shoulder function and passive joint mechanics were evaluated over time. Tendon mechanical, histological, organizational, and compositional properties were evaluated at both time points. Gross observation demonstrated alterations in scapular motion, consistent with scapular “winging.” Shoulder function, passive internal range of motion, and tendon mechanical properties were significantly altered. Histology results, consistent with tendon pathology (rounded cell shape and increased cell density), were observed, and protein expression of collagen III and decorin was altered. This study presents a new model of scapular dyskinesis that can rigorously evaluate cause and effect relationships in a controlled manner. Our results identify scapular dyskinesis as a causative mechanical mechanism for shoulder tendon pathology. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1436–1443, 2014.
Group Trauma‐Informed Treatment for Adolescent Psychiatric Inpatients: A Preliminary Uncontrolled Trial
Authors: Gudiño Omar G. , Weis J. Rebecca , Havens Jennifer F. , Biggs Emily A. , Diamond Ursula N. , Marr Mollie , Jackson Christie , Cloitre Marylene
Published: July 2014

Despite high rates of trauma exposure (46%‐96%) and significant posttraumatic stress disorder (PTSD; 21%–29%) symptoms in adolescent psychiatric inpatients, there is a dearth of research on effective interventions delivered in inpatient settings. The current report describes the development of Brief STAIR‐A, a repeatable 3‐module version of skills training in affective and interpersonal regulation (STAIR) developed for adolescents in inpatient care. An uncontrolled design was used to conduct a preliminary examination of the group intervention's effectiveness. Adolescent psychiatric inpatients (N = 38; ages 12 years–17 years) admitted to a public hospital participated in Brief STAIR‐A and attended a median of 6 sessions (range 3–36). They completed measures of PTSD and depressive symptom severity, coping skill use, and coping efficacy upon admission and again prior to discharge. Participants reported significant reductions in symptom severity (d = 0.65–0.67), no change in the absolute level of coping skills used (d = 0.16), but greater coping efficacy when discharged from care (d = 0.75). Results from this pilot study suggest that this brief group treatment shows promise for treating adolescents’ trauma‐related difficulties in inpatient psychiatry settings, but additional research examining its effectiveness is essential.