bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of burnout with doctor–patient relationship and common stressors among postgraduate trainees and house officers in Lahore—a cross-sectional study
Authors: Ahmad Waqas , Ashraf Huma , Talat Afnan , Khan Aleena Ahmad , Baig Ammad Anwar , Zia Iqra , Sarfraz Zohak , Sajid Hifsa , Tahir Marium , Sadiq Usman , Imtiaz Hira
Published: September 2018

Introduction

Burnout is defined as a prolonged state of physical and psychological exhaustion. Doctors, due to the demanding nature of their job, are susceptible to facing burnout, which has far reaching implications on their productivity and motivation. It affects the quality of care they provide to patients, thus eroding the doctor–patient relationship which embodies patient centeredness and autonomy. The study aims at addressing the stressors leading to burnout and its effect on the doctor–patient relationship.

Methods

A descriptive, cross-sectional study design with convenience (non-probability) sampling technique was employed in six major hospitals of Lahore, Pakistan. A total of 600 doctors were approached for the study which included house officers or “HOs” (recent graduates doing their 1 year long internship) and post-graduate trainees or “PGRs” (residents for 4–5 years in their specialties). Burnout was measured using the Copenhagen Burnout Inventor (CBI) while attitudes towards the doctor–patient relationship was measured using the Patient Practitioner Orientation Scale (PPOS), which measures two components of the relationship: power sharing and patient caring. Pearson correlation and linear regression analysis were used to analyze the data via SPSS v.21.

Results

A total of 515 doctors consented to take part in the study (response rate 85.83%). The final sample consisted of 487 doctors. The burnout score was not associated with the total and caring domain scores of PPOS (P > 0.05). However, it was associated with the power sharing sub-scale of PPOS. Multiple linear regression analysis yielded a significant model, by virtue of which CBI scores were positively associated with factors such as female gender, feeling of burn out, scoring high on sharing domain of PPOS and a lack of personal control while CBI scores were negatively associated with private medical college education, having a significant other, accommodation away from home and a sense of never ending competition. Burnout levels varied significantly between house officers and post graduate trainees. Twenty-three percent of the participants (mostly house officers) had high/very high burnout levels on the CBI (Kristenson’s burnout scoring). Both groups showed significant differences with respect to working hours, smoking status and income.

Conclusion

Although burnout showed no significant association with total and caring domain scores of PPOS (scale used to assess doctor–patient relationship), it showed a significant association with the power sharing domain of PPOS suggesting some impact on the overall delivery of patient care. Thus, it necessitates the monitoring of stressors in order to provide an atmosphere where patient autonomy can be practiced.
Short‐term tamoxifen treatment has long‐term effects on metabolism in high‐fat diet‐fed mice with involvement of Nmnat2 in POMC neurons
Authors: Liu Zhiyuan , Cheng Yalan , Luan Yi , Zhong Wuling , Lai Hejin , Wang Hui , Yu Huimin , Yang Yale , Feng Ning , Yuan Feixiang , Huang Rui , He Zhishui , Zhang Fang , Yan Menghong , Yin Hao , Guo Feifan , Zhai Qiwei
Published: September 2018

Short‐term tamoxifen treatment has effects on lipid and glucose metabolism in mice fed chow. However, its effects on metabolism in mice fed high‐fat diet (HFD) and the underlying mechanisms are unclear. Here, we show that tamoxifen treatment for 5 days decreases fat mass for as long as 18 weeks in mice fed HFD. Tamoxifen alters mRNA levels of some genes involved in lipid metabolism in white adipose tissue and improves glucose and insulin tolerance as well as hepatic insulin signaling for 12–20 weeks. Proopiomelanocortin (POMC) neuron‐specific deletion of nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) attenuates the effects of tamoxifen on glucose and insulin tolerance. These data demonstrate that short‐term injection of tamoxifen has long‐term effects on lipid and glucose metabolism in HFD mice with involvement of Nmnat2 in POMC neurons.
Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels
Authors: Nakamura Takumi , Kawarabayashi Takeshi , Seino Yusuke , Hirohata Mie , Nakahata Naoko , Narita Sakiko , Itoh Ken , Nakaji Shigeyuki , Shoji Mikio
Published: September 2018

Objective

The aim of this study was to confirm determinative factors for plasma Aβ and its association with cognitive function.

Methods

Fasting plasma Aβ40 and Aβ42 levels were measured by ELISA in 1019 participants in the Iwaki Health Promotion Project. The relationships between plasma Aβ and health‐related items, including physical characteristics, cognitive function tests, blood chemistry, and APOE‐ε4 genotype were analyzed.

Results

The plasma levels of Aβ40 and Aβ42, and Aβ40/42 ratio were found to significantly increase with aging. The age‐dependent increase in Aβ42 level was significantly suppressed by APOE‐ε4. Renal function was an associated factor for the plasma Aβ40 level. The plasma Aβ42 level and Aβ40/42 ratio correlated with cognitive function.

Interpretation

Age and APOE‐ε4 are major determinative factors of plasma levels of Aβ42 and the Aβ40/42 ratio. These factors are critical adjustment factors for the usage of plasma Aβ as a biomarker of central nervous system amyloidosis.
Psoriatic Arthritis Disease Activity During and After Pregnancy: A Prospective Multicenter Study
Authors: Ursin Kristin , Lydersen Stian , Skomsvoll Johan F. , Wallenius Marianne
Published: September 2018

Objective

To study disease activity in women with peripheral psoriatic arthritis (PsA) during and after pregnancy. Previous knowledge on this topic is sparse.

Methods

The study included 108 pregnancies in 103 women with PsA from a Norwegian nationwide register. Disease activity was assessed prospectively at 7 time points before, throughout, and after pregnancy with the 3‐variable Disease Activity Score in 28 joints (DAS28) using C‐reactive protein levels and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Scores assessed at each time point were analyzed in a linear mixed model. We did additional analyses with “tumor necrosis factor inhibitor (TNFi) in pregnancy” as a covariate. The same statistical method was used to study self‐reported physical function, pain, and mental health.

Results

Approximately 75% of the women were in remission or had low disease activity during and after pregnancy according to the DAS28‐CRP score. Although disease activity was altogether stable, we found that it decreased in pregnancy and increased within 6 months postpartum. Disease activity at 6 months postpartum was significantly higher than at 6 weeks postpartum (mean DAS28‐CRP score 2.71 versus 2.45; P = 0.016). Women using TNFi in pregnancy had significantly lower disease activity than women not using TNFi (mean DAS28‐CRP score at 6 months postpartum 2.22 versus 2.72; P = 0.043). BASDAI scores were also low and stable during pregnancy but significantly higher at 6 months postpartum than at 6 weeks postpartum (mean BASDAI score 3.69 versus 2.95; P = 0.013).

Conclusion

Studying women with PsA, we found that disease activity was highest at 6 months postpartum but altogether low and stable in the period from planning pregnancy to 1 year after delivery. Women using TNFi in pregnancy had significantly lower disease activity.
Data‐driven approach for fault detection and isolation in nonlinear system
Authors: Kallas Maya , Mourot Gilles , Maquin Didier , Ragot José
Published: September 2018

System diagnosis has been of a great interest for all aspects of industrial processes more precisely to gain in quality. It is based essentially on the analysis of the links between the variables of a system and more precisely on the changes of the relations between these variables, which testify to the presence of faults or anomalies. For that purpose, data modeling is the process of finding a mathematical expression that provides a good fit between given finite sample values of the independent variables and the associated values of the dependent variables of the process.

The aim of this paper is to detect and, above all, localize faults affecting a system with nonlinear behavior, when its model is not known a priori. An important part of the presentation is dedicated to the construction of fault indicators capable of locating faults, ie, recognizing the input or output of a system affected by a fault. The first part of this paper is devoted to how to predict the output of a nonlinear behavior system. The second part proposes a way for the detection and isolation of measurement faults based on the proposed prediction model. The relevance of the proposed technique, for modeling and system diagnosis, is illustrated on a simulated example in the context of SIMO and MIMO systems.
Raised serum cystatin C can be a potential biomarker of frailty detected by cumulative deficit model
Authors: Gunasekaran Venugopalan , Dey Sharmistha , Chakrawarty Avinash , Chatterjee Prashun , Sati Hem Chandra , Dwivedi Sada Nand , Dey Aparajit Ballav
Published: September 2018

Objective

Identification of frailty by clinical criteria is often delayed to the advanced stage. A reliable biomarker to identify frailty or its risk does not currently exist. We aimed to determine the association between serum cystatin C and frailty in subjects without renal dysfunction.

Methods

We carried out a cross‐sectional observational study in the Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India. The study involved 125 participants, aged 65 years or older. Frailty status was assessed with Frailty Index criteria (cumulative deficit model). Serum cystatin C was estimated with the nephelometry method and its association with frailty was analyzed.

Results

Mean age of the study sample was 76.32 years with 72 (57.6%) male and 53 (42.4%) female participants. Seventy‐three subjects were frail; the mean cystatin C levels in the frail and non‐frail groups were 1.28 mg/L (±0.39) and 1.12 mg/L (±0.27), respectively, and the difference was significant (P < 0.05). A cutoff of 1.12 mg/L was found to be 60.27% sensitive and 57.69% specific in identification of frailty. Multivariate analysis showed that higher cystatin C level was associated with 2.52 (1.05‐6.02) times the risk of being frail.

Conclusion

Higher levels of cystatin C were found in frail subjects. Cystatin C seems to be a promising marker for identifying frailty in older adults without renal abnormalities.
The daily grind: Sex‐ and age‐related activity patterns inferred from cross‐sectional geometry of long bones in a pre‐Columbian muisca population from Tibanica, Colombia
Authors: Miller Melanie J. , Agarwal Sabrina C. , Aristizabal Lucero , Langebaek Carl
Published: September 2018

Objectives

Daily activities involve biomechanical strains acting on skeletal structures. This study identifies differences in activity patterns between males and females, and between young, middle, and older aged individuals within an excavated Muisca skeletal sample from the Eastern Andes region of Northern South America.

Materials and methods

The Tibanica archaeological site (AD 1000‐1400) is located at 2600 masl on the Sabana de Bogotá, Colombia. Cross‐sectional geometric analysis of femurs from 63 individuals and paired‐humerii from 33 individuals was used to examine bone size (TA), strength (J) and diaphyseal shape (Imax/Imin, Ix/Iy).

Results

The findings indicate both age‐ and sex‐related differences in activity patterns. An emphasis on upper body strength and robusticity was observed in the females, while males performed more strenuous work using their lower bodies, suggesting gender‐based differences in labor. Men showed significant asymmetry in their humerii, with most showing right‐hand dominance for upper body activities, while females showed high levels of humeral symmetry indicating similar levels of biomechanical stress for both arms. Female femoral diaphyseal shape changes with age, suggesting more mobility in youth and decreased mobility in middle and older ages.

Discussion

These results suggest that daily life may have been structured through patterns of routine labor that united and divided particular age and sex groups. Cross‐sectional geometry data indicate women likely spent significant time and energy preparing food, especially grinding maize or other foods, while men may have done more long‐distance walking potentially to work in agricultural fields or procure other resources.
Katalytische, isofunktionelle Reaktionen – Erweiterung des Repertoires an Shuttle‐ und Metathesereaktionen
Authors: Bhawal Benjamin N. , Morandi Bill
Published: September 2018

Transferhydrierungsreaktionen, genauso wie Metathesereaktionen von Alkenen und Alkinen, sind von großer Bedeutung in der Synthesechemie. Ein gemeinsames Schlüsselmerkmal dieser Verfahren ist ihre Reversibilität, die davon herrührt, dass sowohl Startverbindungen als auch Produkte die gleiche Anzahl und Art von funktionellen Gruppen aufweisen und die Verfahren somit isofunktionell machen. Diese klassischen Reaktionen trugen in letzter Zeit dazu bei, neuartige Shuttle‐ und Metathesereaktionen zu entwickeln, die vielversprechend für die Synthesechemie sein könnten. Dieser Aufsatz beschreibt und ordnet aktuelle wie auch ältere Beispiele von Shuttle‐ und Metathesereaktionen (mit Ausnahme von Transferhydrierungen und Metathesereaktionen von Alkenen und Alkinen).
Dynamic Kinetic Asymmetric Reductive Amination: Synthesis of Chiral Primary β‐Amino Lactams
Authors: Lou Yazhou , Hu Yutao , Lu Jiaxiang , Guan Fanfu , Gong Gelin , Yin Qin , Zhang Xumu
Published: September 2018

A highly efficient ruthenium‐catalyzed asymmetric reductive amination (ARA) of racemic β‐keto lactams with molecular hydrogen and ammonium salts is disclosed for the synthesis of enantiomerically pure primary amino lactams through dynamic kinetic resolution (DKR). By this approach, a range of syn primary β‐amino lactams were obtained in high yields with high chemo‐, enantio‐, and diastereoselectivity (up to 98 % yield, 99 % ee, >20:1 d.r., syn products). The utility of the products has been demonstrated by rapid access to a key synthetic intermediate towards biologically active drug molecules. Meanwhile, mechanistic studies and control experiments indicate that the reaction may proceed through the hydrogenation of an iminium intermediate.
Total Syntheses of Asperchalasines A–E
Authors: Bao Ruiyang , Tian Chong , Zhang Haoyu , Wang Zhiguo , Dong Zhen , Li Yuanhe , Gao Mohan , Zhang Haolin , Liu Gang , Tang Yefeng
Published: September 2018

The first total syntheses of asperchalasines A–E, a collection of unprecedented merocytochalasans, are reported. Aspochalasin B, a key tricyclic cytochalasan monomer, was first synthesized through a unified approach that hinges on a Diels–Alder reaction and a ring‐closing metathesis reaction. The bioinspired Diels–Alder reactions of aspochalasin B with different epicoccine precursors were then explored, which enabled the divergent access of the heterodimers asperchalasines B–E as well as related congeners. Furthermore, the heterotrimer asperchalasine A was obtained from one epicoccine unit and two aspochalasin B units through a biomimetic Diels–Alder reaction followed by an oxidative [5+2]‐cycloaddition.
Enantioselective Functionalization of Enamides at the β‐Carbon Center with Indoles
Authors: Saputra Mirza A. , Nepal Binod , Dange Nitin S. , Du Pu , Fronczek Frank R. , Kumar Revati , Kartika Rendy
Published: September 2018

We report an enantioconvergent approach for the functionalization of enamides at the β‐carbon atom, which involves a chiral Brønsted acid induced tautomerization of 2‐amidoallyl into 1‐amidoallyl cations. These putative reactive intermediates were produced by ionization of racemic α‐hydroxy enamides with a chiral Brønsted acid and captured with substituted indoles in a highly regio‐ and enantioselective manner.
Chemical Probes for Human UDP‐Glucuronosyltransferases: A Comprehensive Review
Authors: Lv Xia , Zhang Jian‐Bin , Hou Jie , Dou Tong‐Yi , Ge Guang‐Bo , Hu Wen‐Zhong , Yang Ling
Published: September 2018

UGTs play crucial roles in the metabolism and detoxification of both endogenous and xenobiotic compounds. The key roles of UGTs in human health have garnered great interest in the design and development of specific probes for human UGTs. However, in contrast to other human enzymes, the probe substrates for human UGTs are rarely reported, owing to the highly overlapping substrate specificities of UGTs and the lack of the integrated crystal structures of UGTs. Over the past decades, many efforts are made to develop specific probe substrates for UGTs and use them in both basic research and drug discovery. This review focuses on recent progress in the development of probe substrates for UGTs and their biomedical applications. A long list of chemical probes for UGTs, including non‐fluorescent and fluorescent probes along with their structural information and kinetic parameters, are prepared and analyzed. Additionally, challenges and future directions in this field are highlighted in the final section. All information and knowledge presented in this review provide practical tools/methods for measuring UGT activities in complex biological samples, which will be very helpful for rapid screening and characterization of UGT modulators, and for exploring the relevance of UGT enzymes to human diseases.
Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones
Authors: Ai Huasong , Guo Yu , Sun Demeng , Liu Sanling , Qi Yunkun , Guo Jing , Qu Qian , Gong Qingyue , Zhao Suwen , Li Jiabin , Liu Lei
Published: September 2018

Histone ubiquitylation and deubiquitylation processes and the mechanisms of their regulation are closely relevant to the field of epigenetics. Recently, the deubiquitylating enzyme USP51 was reported to selectively cleave ubiquitylation on histone H2A at K13 or K15 (i.e., H2AK13Ub and H2AK15Ub), but not at K119 (i.e., H2AK119Ub), in nucleosomes in vivo. To elucidate the mechanism for the selectivity of USP51, we constructed structurally well‐defined in vitro protein systems with a ubiquitin modification at precise sites. A total chemical protein synthesis procedure was developed, wherein hydrazide‐based native chemical ligation was used to efficiently generate five ubiquitylated histones (H2AK13Ub, H2AK15Ub, H2AK119Ub, H2BK34Ub, and H2BK120Ub). These synthetic ubiquitylated histones were assembled into nucleosomes and subjected to in vitro USP51 deubiquitylation assays. Surprisingly, USP51 did not show preference between H2AK13/15Ub and H2AK119Ub, in contrast to previous in vivo observations. Accordingly, an understanding of the selectivity of USP51 may require consideration of other factors, such as alternative pre‐existing histone modifications, competitive reader proteins, or different nucleosome quality among the in vivo extraction nucleosome and the in vitro reconstitution one. Further experiments established that USP51 in vitro could deubiquitylate a nucleosome carrying H2BK120Ub, but not H2BK34Ub. Molecular dynamics simulations suggested that USP51‐catalyzed hydrolysis of ubiquitylated nucleosomes was affected by steric hindrance of the isopeptide bond.
A Photoenzymatic NADH Regeneration System
Authors: Höfler Georg T. , Fernández‐Fueyo Elena , Pesic Milja , Younes Sabry H. , Choi Eun‐Gyu , Kim Yong H. , Urlacher Vlada B. , Arends Isabel W. C. E. , Hollmann Frank
Published: September 2018

A photoenzymatic NADH regeneration system was established. The combination of deazariboflavin as a photocatalyst with putidaredoxin reductase enabled the selective reduction of NAD+ into the enzyme‐active 1,4‐NADH to promote an alcohol dehydrogenase catalysed stereospecific reduction reaction. The catalytic turnover of all the reaction components was demonstrated. Factors influencing the efficiency of the overall system were identified.
A Sustainable Method for the Synthesis of Acetic Acid Based on Dehydrogenation of an Ethanol–Water Solution Catalyzed by an Iridium Complex Bearing a Functional Bipyridonate Ligand
Authors: Kuwahara Masato , Nishioka Masaaki , Yoshida Masato , Fujita Ken‐ichi
Published: September 2018

The front cover artwork for issue 17/2018 is provided by Prof. Ken‐ichi Fujita′s group from Kyoto University, Japan. The image shows the synthesis of acetic acid via dehydrogenation of a mixture of ethanol and water using a new iridium catalyst bearing a functional bipyridonate ligand with N,N‐dimethylamino substituents. See the Communication itself at https://doi.org/10.1002/cctc.201800680.
Ectonucleotidase Inhibitory and Redox Activity of Imidazole‐Based Organic Salts and Ionic Liquids
Authors: Boldescu Veaceslav , Sucman Natalia , Hassan Sidra , Iqbal Jamshed , Neamtu Mariana , Lecka Joanna , Sévigny Jean , Prodius Denis , Macaev Fliur
Published: September 2018

Cytotoxicity against cancer and normal cells, inhibition of ectonucleotidase, and redox properties of a new group of imidazole‐based organic salts and ionic liquids were studied. The tetrachloroferrate salt of a 1‐methylimidazole derivative of salicylic aldehyde had most prominent inhibitory activity against ectonucleotidase as well as a higher cytotoxicity against HeLa cells and lower cytotoxicity against BHK‐21 cells than the reference compound carboplatin. The studied compounds exhibited a moderate level of antioxidant activity with better results for the salicylic aldehyde derivatives than for spiropyrans. Moreover, these compounds did not generate singlet oxygen.
Optimistic, realistic, and pessimistic illness perceptions; quality of life; and survival among 2457 cancer survivors: the population‐based PROFILES registry
Authors: de Rooij Belle H. , Thong Melissa S.Y. , van Roij Janneke , Bonhof Cynthia S. , Husson Olga , Ezendam Nicole P. M.
Published: September 2018

BACKGROUND

Threatening illness perceptions (IPs) have been associated with poorer health outcomes. However, to the authors' knowledge, it remains unclear whether threatening IPs that are consistent with disease severity are equally harmful. The aim of the current study was to: 1) identify subgroups of cancer survivors based on IPs and prognosis; and 2) assess the health‐related quality of life (HRQOL) and survival associated with these subgroups.

METHODS

The authors used survey data from the population‐based Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry, which were collected between 2008 and 2015 and included 2457 cancer survivors who were <5 years after their cancer diagnosis (colon, rectal, prostate, endometrial, or ovarian cancer or non‐Hodgkin lymphoma). Clinical and survival data were collected through the Netherlands Cancer Registry. Subgroups were defined by IPs (Brief Illness Perception Questionnaire) and prognosis (conditional 5‐year relative survival) into survivors with 1) IPs consistent with prognosis (“realistic”); 2) less threatening IPs than expected based on prognosis (“optimistic”); and 3) more threatening IPs than expected based on prognosis (“pessimistic”).

RESULTS

Compared with survivors with realistic IPs (1230 survivors), those with optimistic IPs (582 survivors) were found to have a higher HRQOL (P < .01 on all European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ‐C30] scales) and a lower all‐cause mortality (hazard ratio, 0.72; P < .01), whereas those with pessimistic IPs (645 survivors) had a lower HRQOL (P < .01 on all scales) and a higher all‐cause mortality (hazard ratio, 1.52; P < .01).

CONCLUSIONS

Optimistic IPs are associated with better HRQOL and survival, even if they may appear to be unrealistic with respect to cancer survivors' prognosis. Survivors with pessimistic IPs appear to have the worst outcomes. Therefore, efforts are needed to provide better support to patients with pessimistic IPs to improve their outcomes. Cancer 2018;124:3609‐17. © The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Towards scalable pattern‐based optimization for dense linear algebra
Authors: Berényi Dániel , Leitereg András , Lehel Gábor
Published: September 2018

Linear algebraic expressions are the essence of many computationally intensive problems, including scientific simulations and machine learning applications. However, translating high‐level formulations of these expressions to efficient machine‐level representations is far from trivial: developers should be assisted by automatic optimization tools so that they can focus their attention on high‐level problems, rather than low‐level details. The tractability of these optimizations is highly dependent on the choice of the primitive constructs in terms of which the computations are to be expressed. In this work, we propose to describe operations on multi‐dimensional arrays using a selection of higher‐order functions, inspired by functional programming, and we present rewrite rules for these such that they can be automatically optimized for modern hierarchical and heterogeneous architectures. Using this formalism, we systematically construct and analyze different subdivisions and permutations of the dense matrix multiplication problem.
Anion Exchange at the Liquid/Solid Interface of Ultrathin Ionic Liquid Films on Ag(111)
Authors: Lexow Matthias , Heller Bettina S. J. , Maier Florian , Steinrück Hans‐Peter
Published: September 2018

Thin ionic liquid (IL) films play an important role in many applications. To obtain a better understanding of the ion distribution within IL mixture films, we sequentially deposited ultrathin layers of two ILs with the same cation but different anions onto Ag(111), and monitored their dynamic behaviour by angle‐resolved X‐ray photoelectron spectroscopy. Upon depositing [C8C1Im][PF6] on top of a wetting layer of [C8C1Im][Tf2N] at room temperature (RT), we found a pronounced enrichment of the [Tf2N]− anions at the IL/vacuum interface, due to a rapid anion exchange at the IL/solid interface. In contrast, at 90 K, the [Tf2N]− anions remain at the IL/solid interface. Upon heating, we observe a rearrangement of the cations between 140 and 160 K, such that the octyl chains preferentially point towards the vacuum. Above 170 K, the ions start to become mobile, and at 220 K, the anion exchange is completed, with the [Tf2N]− anions enriched at the IL/vacuum interface in the same way as found for deposition at RT. The temperature range for the anion exchange corresponds well to glass transition temperatures reported in literature. We propose two driving forces to be cooperatively responsible for the replacement/exchange of [Tf2N]− at the IL/solid interface and its enrichment at the IL/vacuum interface. First, the adsorption energy of [C8C1Im][PF6] is significantly larger than that of [C8C1Im][Tf2N], and second, the surface tension of [C8C1Im][Tf2N] is lower than that of [C8C1Im][PF6].
Pancreatic Beta Cell Differentiation From Human Pluripotent Stem Cells
Authors: Sui Lina , Leibel Rudolph L. , Egli Dieter
Published: September 2018

Insulin‐expressing beta cells are crucial for the maintenance of systemic glucose homeostasis. Elucidation of the molecular and cellular mechanisms of beta cell development, expansion, survival, and function are required for full understanding of the molecular pathogenesis of diabetes. However, access to human beta cells for such studies is limited by virtue of the logistics of acquisition, prior medical status of donor, and imperfect culture systems for maintaining beta cell identity and function after isolation from human pancreas. Here, a technique for generation of beta cells from human pluripotent stem cells (hPSCs) by modification of key signaling pathways during islet development is described. Up to 70% C‐peptide–positive beta cells can be obtained from endodermal anlagen after 27 days of differentiation with specific growth factors and small molecules. Although 50% of them are monohormonal C‐peptide–positive cells and have molecular and cellular characteristics consistent with human beta cells in the Islets of Langerhans, a sub‐population co‐expressing other endocrine markers are also generated, indicating the immaturity of these cells. © 2018 by John Wiley & Sons, Inc.
Mechanistic Study of the Synergy between Iron and Transition Metals for the Catalysis of the Oxygen Evolution Reaction
Authors: Gong Luo , Koh Jiarui , Yeo Boon Siang
Published: September 2018

A comprehensive study of the synergy between Fe and six transition metals (M=Ti, Co, Ni, Cu, Ag, Au), and how their M–Fe oxides electrocatalyze the oxygen evolution reaction (OER) was undertaken. Measurements were made using metal disks as the working electrodes and the addition of Fe3+ ions to the 1 m KOH electrolyte. The surfaces of the metal disks were oxidized after the OER. Interestingly, Fe interacted synergistically with all metal oxide layers except for that of Ti, resulting in enhanced catalytic activity for the OER. At an overpotential (η) of 400 mV, the current densities of the Ni and Ag disks in the Fe3+ ions‐spiked electrolyte increased by 253 and 132 times, respectively, whereas it was only 20–30 times for the Co and Cu disks (compared with the OER in pure KOH at η=400 mV). The Tafel slopes of the Fe, Co, Ni, Cu, and Ag disks in 1 m KOH+Fe3+ electrolyte were in the range of 29–42 mV dec−1. The surface morphology and post‐OER concentration of Fe in the catalysts could not be used to account for differences in the OER activities. Cyclic voltammetry showed that improvements in the OER performance were accompanied by changes in the redox features of the metal disk electrodes, which indicated the presence of electronic interactions between them and the Fe3+. Strikingly, this was not observed between Ti and the Fe3+ ions, which could explain the lack of synergy between Ti and Fe3+ towards the OER catalysis. Electrochemical impedance spectroscopy indicated that the charge‐transfer resistances of all the electrodes (except Ti) decreased after the addition of Fe3+ ions. Fe plays an important role in all these observed phenomena and we propose that the surface‐adsorbed Fe species serve as the main active sites for OER in these synergistic M–Fe combinations.
A causality dilemma: ARFID, malnutrition, psychosis, and hypomagnesemia
Authors: Wassenaar Elizabeth , O'Melia Anne Marie , Mehler Philip S
Published: September 2018

We present a novel case of a woman with coincident occurrence of auditory and visual hallucinations, electrolyte disturbances, chloride unresponsive alkalosis, and an eating disorder. The patient was ultimately diagnosed with Gitelman syndrome comorbid with schizophreniform disorder and avoidant restrictive food intake disorder. Eating disorders are often associated with electrolyte abnormalities which, in turn, can cause or contribute to other neuropsychiatric symptoms. At the same time, psychotic disorders can lead to food intake aversions or overconsumption of fluids with associated effects on electrolyte balance. In this case, a third factor, Gitelman syndrome, resulted in persistent hypomagnesemia with metabolic alkalosis and, while separate from her eating disorder, simultaneously reinforced the patient's strong food preferences, excessive fluid intake, and excessive movement related to her complaints of persistent joint pain.
Gender differences in eating disorder psychopathology across DSM‐5 severity categories of anorexia nervosa and bulimia nervosa
Authors: Zayas Lazaro V. , Wang Shirley B. , Coniglio Kathryn , Becker Kendra , Murray Helen B. , Klosterman Eric , Kay Brian , Bean Pamela , Weltzin Theodore , Franko Debra L. , Eddy Kamryn T. , Thomas Jennifer J.
Published: September 2018

Objective

This study examined whether patterns of eating‐disorder (ED) psychopathology differed by gender across DSM‐5 severity specifiers in anorexia nervosa (AN) and bulimia nervosa (BN).

Method

We tested whether ED psychopathology differed across DSM‐5 severity specifiers among 532 adults (76% female) in a residential treatment center with AN or BN. We hypothesized that severity of ED psychopathology would increase in tandem with increasing severity classifications for both males and females with AN and BN.

Results

Among females with BN, DSM‐5 severity categories were significantly associated with increasing ED psychopathology, including Eating Disorder Examination‐Questionnaire dietary restraint, eating concern, shape concern, and weight concern; and Eating Disorder Inventory drive for thinness and bulimia. ED psychopathology did not differ across DSM‐5 severity levels for males with BN. For both males and females with AN, there were no differences in ED psychopathology across severity levels.

Discussion

Results demonstrate that DSM‐5 severity specifiers may function differently for males versus females with BN. Taken together, data suggest DSM‐5 severity specifiers may not adequately capture severity, as intended, for males with BN and all with AN. Future research should evaluate additional clinical validators of DSM‐5 severity categories (e.g., chronicity, treatment non‐response), and consider alternate classification schemes.
Activation of protein phosphatase 1 by a selective phosphatase disrupting peptide reduces sarcoplasmic reticulum Ca2+ leak in human heart failure
Authors: Fischer Thomas H. , Eiringhaus Jörg , Dybkova Nataliya , Saadatmand Alireza , Pabel Steffen , Weber Silvio , Wang Yansong , Köhn Maja , Tirilomis Theodor , Ljubojevic Senka , Renner André , Gummert Jan , Maier Lars S. , Hasenfuß Gerd , El‐Armouche Ali , Sossalla Samuel
Published: September 2018

Background

Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII‐dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown.

Methods and results

Human myocardium from three groups of patients was investigated: (i) healthy controls (non‐failing, NF, n = 8), (ii) compensated hypertrophy (Hy, n = 16), and (iii) end‐stage heart failure (HF, n = 52). Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its endogenous inhibitor‐1 (I‐1) was markedly lower expressed in both compared to NF, suggesting increased total PP1 activity. In contrast, PP2A expression was lower in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective activation of PP1 by a PP1‐disrupting peptide (PDP3) in HF potently reduced SR Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise systolic Ca2+ release and SR Ca2+ load.

Conclusion

This study is the first to functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased human myocardium. Our data indicate that a modulation of phosphatase activity potently impacts Ca2+ cycling properties. An activation of PP1 counteracts increased kinase activity in heart failure and successfully seals the arrhythmogenic SR Ca2+ leak. It may thus represent a promising future antiarrhythmic therapeutic approach.
Further evidence for sustainable alternatives to replace threatened animal horn based on quantitative proteomic analysis
Authors: Liu Rui , Huang Qiong , Zhu Zhenhua , Zhang Yan , Qian Dawei , Duan Jin‐Ao
Published: September 2018

In the present study, a quantitative proteomic approach was used to analyze and compare the proteome in horns from endangered species (rhinoceros, Saiga antelope, and Tibetan antelope) and common species (yak, water buffalo, and goat) based on the isobaric tag for relative and absolute quantification techniques. In total, 591 proteins were identified, and 321 were quantified and categorized based on molecular function, cellular component, and biological process. Principal component analysis and hierarchical clustering analysis results based on differences in the amount of protein identified three major clusters, and proteins including transglutaminase, desmocollin, and elongation factors were selected as trait components from proteomic patterns of horn samples from different species. Quantitative proteomic analysis based strategies can therefore provide further evidence for sustainable alternatives to replace animal horn from threatened species.
Rosmarinic acid‐loaded electrospun nanofibers: In vitro release kinetic study and bioactivity assessment
Authors: Vatankhah Elham
Published: September 2018

This study seeks to develop a nanofibrous matrix containing rosmarinic acid (RosA), an herbal non‐steroidal anti‐inflammatory and antioxidant drug with low water solubility, for drug delivery applications. Neat and two types of RosA‐loaded cellulose acetate (CA) mats varying in the initial content of RosA were electrospun. Microstructure of nanofibers, chemistry and physical state of RosA in nanofibers, RosA loading efficiency and RosA release in acetate buffer were investigated. To evaluate bioactivity of RosA‐loaded nanofibers, their ability to inhibit protein denaturation was assayed as an indicator of anti‐inflammatory properties and their antioxidant activity was determined by radical scavenging assay. The indirect cytotoxicity assay was used to find if there is a cytotoxic response to nanofibers. The homogeneous distribution of the drug within nanofibers through electrospinning led to high loading efficiency, low burst release and prolonged release of a large percentage of RosA over a period of 64h following Fickian diffusion mechanism. Nanofibers with higher RosA content exhibited anti‐inflammatory activity comparable to ibuprofen, and higher antioxidant activity compared to nanofibers with lower RosA content. Additionally, extracts from nanofibers did not give any major harmful effect on cells. Sustained release of RosA, and bioactivity of RosA‐loaded nanofibers confirmed the potential of the produced matrix as a drug delivery system.
Performance of viscous damping in inelastic seismic analysis of moment‐frame buildings
Authors: Hall John F.
Published: September 2018

This paper investigates the performance of viscous damping in the inelastic seismic analysis of moment‐frame buildings using a detailed model of a 20‐story steel structure. Damping schemes included are Rayleigh, condensed Rayleigh, Wilson‐Penzien, tangent Rayleigh, elastic velocity Rayleigh, and capped damping. Caughey damping is found not to be computationally viable. Differences among the damping schemes, as quantified by plastic hinge rotations and story drifts, become noticeable once these quantities reach the 3% level. In order of least to greatest hinge rotations and story drifts that occur under lateral response to horizontal ground motion, the damping schemes rank as Rayleigh (most damping action), condensed Rayleigh, Wilson‐Penzien, tangent Rayleigh and capped damping, which are about the same, and elastic velocity Rayleigh (least damping action). Performance of Rayleigh damping under vertical ground motion is discussed, including the effect of soil‐structure interaction. The propensity of Rayleigh damping to generate excessive damping forces and moments during inelastic seismic analysis is explained, and a parameter is introduced that can predict the potential magnitude of the effect. A review of some literature on amplified Rayleigh damping moments is also presented.
The U.S. Federal Evaluation Market
Authors: Lemire Sebastian , Fierro Leslie A. , Kinarsky Alana R. , Fujita‐Conrads Emi , Christie Christina A.
Published: September 2018

This chapter describes the main features of the demand side of the U.S. federal evaluation market. The chapter is structured according to three sections. Section one provides a historical account of the overarching developments of the U.S. federal evaluation market, awarding special attention to the legislative drivers of federal funding for evaluation. In logical extension, the second section documents the current federal evaluation funding across the twenty‐two non‐defense departments subject to the provisions in the 2010 Government Performance and Results Modernization Act. Advancing toward a better understanding of the federal procurement and contracting of evaluation, a more fine‐grained analysis of evaluation contracts in the Department of Health and Human Services is provided. Finally, the third section concludes the chapter by summarizing and considering the implications of the findings in relation to evaluation practice.
The Evolving Market for Systematic Evaluation in Canada
Authors: Lahey Robert , Elliott Catherine , Heath Sarah
Published: September 2018

The professionalization of evaluation and the need for educational programs and accreditation has taken on increasing importance in Canada over the 2000s. Central to these issues is the need to understand the nature of the evaluation industry, both from the “supply” and “demand” side. While there have been fragmented discussions about the nature of evaluation in the federal government (e.g., Lahey, 2010; Segsworth, 2005) and the provinces and territories (e.g., Gauthier et al., 2009), there remains a dearth of information about the nature and behavior of the evaluation industry in Canada as a whole. This chapter offers an exploratory investigation into the evaluation industry in Canada, examining both the demand and the supply side, along with a historical context that serves as a backdrop in understanding the current structure of the Canadian industry. The study examines how various factors affect market behavior, and reflects on considerations for the future of the Canadian evaluation industry.
Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Authors: Adam Leonie , Zoldan Katharina , Hofmann Maike , Schultheiss Michael , Bettinger Dominik , Neumann‐Haefelin Christoph , Thimme Robert , Boettler Tobias
Published: September 2018

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases. While PBC is generally accepted to be an autoimmune disorder characterized by pathognomonic autoantibodies against mitochondrial antigens, the pathogenesis of PSC is less precisely defined; however, some degree of altered immunity toward autoantigens has been suggested. Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T‐cell subset specialized in facilitating antibody responses, have been shown to contribute to humoral autoimmunity in various disorders; yet, there is only limited information on possible alterations of Tfh cells in the context of cholestatic liver diseases. Thus, we addressed this important question by analyzing the frequency, activation status, and function of Tfh cells and frequencies of regulatory follicular T helper (Tfr) cells in well‐defined cohorts of patients with PBC and patients with PSC. Interestingly, we observed a significant increase in circulating chemokine (C‐X‐C motif) receptor 5 (CXCR5)+programmed death 1 (PD‐1) +CD4+ Tfh cells in patients with PBC but not in those with PSC. Although the frequency of potentially pathogenic chemokine (C‐C motif) receptor 7 (CCR7)lowCXCR5+PD‐1+CD4+ Tfh cells was increased in both disorders compared to healthy donors, the increase was significantly more pronounced in PBC. Furthermore, in patients with PBC, Tfh cells displayed stronger expression of the activation markers OX40 and inducible costimulator of T cells, correlated with anti‐anti‐mitochondrial antibody M2 and immunoglobulin M titers, and were most significantly increased in patients with cirrhosis. Tfr cell numbers were similarly increased; however, Tfh/Tfr ratios were unaltered in PSC and PBC. These alterations did not correlate with increased secretion of the Tfh signature cytokine interleukin‐21 in sorted CD4 T cells. Conclusion: Significant alterations occur in the Tfh cell compartment in cholestatic liver diseases, suggesting that Tfh cells influence the pathogenesis of PBC and to a lesser extend PSC.
Diagnostic framing of IgM monoclonal gammopathy: Focus on Waldenström macroglobulinemia
Authors: Tedeschi Alessandra , Conticello Concetta , Rizzi Rita , Benevolo Giulia , Laurenti Luca , Petrucci Maria Teresa , Zaja Francesco , Varettoni Marzia
Published: September 2018

The finding of an IgM monoclonal gammopathy often represents a diagnostic challenge. In fact, there are many pathological disorders associated with this condition, each of which has distinctive characteristics and requires specific clinical, instrumental, and laboratory assessments to set the appropriate treatment. This review has two aims. Firstly, to provide a framework of the broad spectrum of IgM‐associated disorders: (1) monoclonal gammopathy of undetermined significance (MGUS); (2) Waldenström macroglobulinemia (WM); (3) IgM‐related disorders (among which hyperviscosity syndrome, light chain amyloidosis, cold agglutinin disease, cryoglobulinaemia, IgM neuropathy, Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome, Castleman disease); (4) IgM‐secreting multiple myeloma (IgM‐MM); and (5) other lymphoproliferative disorders which may be associated with IgM (such as chronic lymphocytic leukemia, small lymphocytic lymphoma, and B‐cell non Hodgkin lymphoma). Secondly, to give a detailed insight regarding diagnosis and treatment of WM.
Genome‐wide microRNA analysis of HPV‐positive self‐samples yields novel triage markers for early detection of cervical cancer
Authors: Snoek Barbara C. , Verlaat Wina , Babion Iris , Novianti Putri W. , van de Wiel Mark A. , Wilting Saskia M. , van Trommel Nienke E. , Bleeker Maaike C.G. , Massuger Leon F.A.G. , Melchers Willem J.G. , Sie Daoud , Heideman Daniëlle A.M. , Snijders Peter J.F. , Meijer Chris J.L.M. , Steenbergen Renske D.M.
Published: September 2018

Offering self‐sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self‐samples are needed to stratify HPV‐positive women at risk of cervical cancer (so‐called triage) and to avoid over‐referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self‐samples. Our study is the first to establish genome‐wide miRNA profiles in HPV‐positive self‐samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self‐samples. Small RNA sequencing (sRNA‐Seq) was conducted to determine genome‐wide miRNA expression profiles in 74 HPV‐positive self‐samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRridge, a penalized method on logistic regression. Six miRNAs were validated by qPCR in 191 independent HPV‐positive self‐samples. Classification of sRNA‐Seq data yielded a 9‐miRNA marker panel with a combined area under the curve (AUC) of 0.89 for CIN3 detection. Validation by qPCR resulted in a combined AUC of 0.78 for CIN3+ detection. Our study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected by sRNA‐Seq in HPV‐positive self‐samples. Validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self‐samples.