bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted sequencing identifies genetic polymorphisms of flavin‐containing monooxygenase genes contributing to susceptibility of nicotine dependence in European American and African American
Authors: Zhang Tian‐Xiao , Saccone Nancy L. , Bierut Laura J. , Rice John P.
Published: March 2017

Background

Smoking is a leading cause of preventable death. Early studies based on samples of twins have linked the lifetime smoking practices to genetic predisposition. The flavin‐containing monooxygenase (FMO) protein family consists of a group of enzymes that metabolize drugs and xenobiotics. Both FMO1 and FMO3 were potentially susceptible genes for nicotine metabolism process.

Methods

In this study, we investigated the potential of FMO genes to confer risk of nicotine dependence via deep targeted sequencing in 2,820 study subjects comprising 1,583 nicotine dependents and 1,237 controls from European American and African American. Specifically, we focused on the two genomic segments including FMO1, FMO3, and pseudo gene FMO6P, and aimed to investigate the potential association between FMO genes and nicotine dependence. Both common and low‐frequency/rare variants were analyzed using different algorithms. The potential functional significance of SNPs with association signal was investigated with relevant bioinformatics tools.

Results

We identified different clusters of significant common variants in European (with most significant SNP rs6674596, p = .0004, OR = 0.67, MAF_EA = 0.14, FMO1) and African Americans (with the most significant SNP rs6608453, p = .001, OR = 0.64, MAF_AA = 0.1, FMO6P). No significant signals were identified through haplotype‐based analyses. Gene network investigation indicated that both FMO1 and FMO3 have a strong relation with a variety of genes belonging to CYP gene families (with combined score greater than 0.9). Most of the significant variants identified were SNPs located within intron regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals.

Conclusions

Our findings indicated significant association between FMO genes and nicotine dependence. Replications of our findings in other ethnic groups were needed in the future. Most of the significant variants identified were SNPs located within intronic regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals.
Bifunctional Tripeptide with a Phosphonic Acid as a Brønsted Acid for Michael Addition: Mechanistic Insights
Authors: Cortes‐Clerget Margery , Jover Jesús , Dussart Jade , Kolodziej Emilie , Monteil Maelle , Migianu‐Griffoni Evelyne , Gager Olivier , Deschamp Julia , Lecouvey Marc
Published: March 2017

Enamine catalysis is a widespread activation mode in the field of organocatalysis and is often encountered in bifunctional organocatalysts. We previously described H‐Pro‐Pro‐pAla‐OMe as a bifunctional catalyst for Michael addition between aldehydes and aromatic nitroalkenes. Considering that opposite selectivities were observed when compared to H‐Pro‐Pro‐Glu‐NH2, an analogue described by Wennemers, the activation mode of H‐Pro‐Pro‐pAla‐OMe was investigated through kinetic, linear effect studies, NMR analyses, and structural modifications. It appeared that only one bifunctional catalyst was involved in the catalytic cycle, by activating aldehyde through an (E)‐enamine and nitroalkene through an acidic interaction. A restrained tripeptide structure was optimal in terms of distance and rigidity for better selectivities and fast reaction rates. Transition‐state modeling unveiled the particular selectivity of this phosphonopeptide.
Fluorinated Unsymmetrical N,N′‐Diaryl Imidazolium Salts—New Functionalized NHC‐Ligand Precursors
Authors: Topchiy Maxim A. , Zotova Maria A. , Masoud Salekh M. , Mailyan Artur K. , Ananyev Ivan V. , Nefedov Sergey E. , Asachenko Andrey F. , Osipov Sergey N.
Published: March 2017

An efficient and scaled‐up synthesis of the imidazol‐2‐ylidene‐based unsymmetrical NHC precursors bearing the sterically demanding hexafluoroisopropylalkoxy group [(CF3)2(OR)C−] at the ortho position of the N‐aryl substituent was developed. The key step of the method involved the transformation of a Mes‐substituted oxazolinium tetrafluoroborate salt through the reaction with the corresponding binucleophilic fluoroalkyl‐substituted aniline. The subsequent post‐modification of the resulting hydroxyl‐containing salt through a simple one‐step O‐alkylation protocol provided access to a new family of unsymmetrical fluorinated NHC precursors. These compounds were successfully utilized for the preparation of several novel metal complexes. The molecular structures of some NHC precursors and their metal complexes have been unambiguously characterized by single‐crystal X‐ray diffraction analysis. A preliminary evaluation of the catalytic activity of the palladium complexes was performed on a Buchwald–Hartwig amination reaction. As a result, two PEPPSI‐type (PEPPSI=pyridine‐enhanced pre‐catalyst preparation stabilization and initiation) Pd complexes have demonstrated promising activity in alkane solvents.
Efficient Benzodithiophene/Benzothiadiazole‐Based n‐Channel Charge Transporters
Authors: Sandoval‐Torrientes Rafael , Calbo Joaquín , Matsuda Wakana , Choi Wookjin , Santos José , Seki Shu , Ortí Enrique , Martín Nazario
Published: March 2017

A series of donor–acceptor (D‐A) small molecules based on electron‐deficient benzothiadiazole (BTD) and electron‐rich benzodithiophene (BDT) featuring an A‐D‐A structure is presented. Exhaustive spectroscopic, electrochemical, and computational studies evidence their electroactive nature and their ability to form well‐ordered thin films with broad visible absorptions and low band gaps (ca. 2 eV). Time‐resolved microwave conductivity (TRMC) studies unveil unexpected n‐type charge transport displaying high electron mobilities around 0.1 cm2 V−1 s−1. Efficient electron transport properties are consistent with the low electron reorganization energies (0.11–0.17 eV) theoretically predicted.
Quantum screened interactions in moderately dense plasmas and atomic contributions to thermodynamics
Authors: Ballenegger V. , Wendland D. , Alastuey A.
Published: March 2017

The screened Coulomb interaction φ through which particles interact in the path integral description of quantum plasmas is studied analytically and numerically. This interaction, which is a key ingredient in quantum Mayer diagrams, is closely related to the random‐phase approximation potential known from finite‐temperature many‐body perturbation theory. An efficient way to compute numerically φ and its contributions in quantum Mayer diagrams under weak degeneracy conditions is proposed. Two key contributions to the thermodynamics of a moderately dense hydrogen plasma are studied using this method: polarization of the plasma and the electron– proton cluster function which accounts for the contributions from hydrogen atoms at finite density and finite temperature. The calculations include effects from dynamical screening and from shifts as well as broadening of spectral lines. When κ λ≪1, with κ the inverse Debye screening length and λ the electronic thermal de Broglie wavelength, a simple fast‐to‐evaluate approximation for φ can be used without loss of accuracy. The error induced on the electron– proton cluster function by the common approximation of replacing φ by a statically screened Debye potential is assessed for κ λ in the range 0⩽κ λ⩽0.5.
Long‐term and widespread changes in agricultural practices influence ring‐necked pheasant abundance in California
Authors: Coates Peter S. , Brussee Brianne E. , Howe Kristy B. , Fleskes Joseph P. , Dwight Ian A. , Connelly Daniel P. , Meshriy Matt G. , Gardner Scott C.
Published: March 2017

Declines in bird populations in agricultural regions of North America and Europe have been attributed to agricultural industrialization, increases in use of agrochemical application, and increased predation related to habitat modification. Based on count data compiled from Breeding Bird Survey (BBS) from 1974 to 2012, Christmas Bird Count (CBC) collected from 1914 to 2013, and hunter data from Annual Game Take Survey (AGTS) for years 1948–2010, ring‐necked pheasants (Phasianus colchicus) in California have experienced substantial declines in agricultural environments. Using a modeling approach that integrates all three forms of survey data into a joint response abundance index, we found pheasant abundance was related to the amount of harvested and unharvested crop land, types of crops produced, amount of total pesticide applied, minimum temperature, precipitation, and numbers of avian competitors and predators. Specifically, major changes in agricultural practices over the last three decades were associated with declines in pheasant numbers and likely reflected widespread loss of habitat. For example, increases in cropland were associated with increased pheasant abundance during early years of study but this effect decreased through time, such that no association in recent years was evidenced. A post hoc analysis revealed that crops beneficial to pheasant abundance (e.g., barley) have declined substantially in recent decades and were replaced by less advantageous crops (e.g., nut trees). An additional analysis using a restricted data set (1990–2013) indicated recent negative impacts on pheasant numbers associated with land use practices were also associated with relatively high levels of pesticide application. Our results may provide valuable information for management policies aimed at reducing widespread declines in pheasant populations in California and may be applicable to other avian species within agricultural settings. Furthermore, this general analytical approach is not limited to pheasants and could be applied to other taxa for which multiple survey data sources exist.
The effect of exercise training on biventricular myocardial strain in heart failure with preserved ejection fraction
Authors: Angadi Siddhartha S. , Jarrett Catherine L. , Sherif Moustafa , Gaesser Glenn A. , Mookadam Farouk
Published: March 2017

Aims

High‐intensity interval training (HIIT) improves peak oxygen uptake and left ventricular diastology in patients with heart failure with preserved ejection fraction (HFpEF). However, its effects on myocardial strain in HFpEF remain unknown. We explored the effects of HIIT and moderate‐intensity aerobic continuous training (MI‐ACT) on left and right ventricular strain parameters in patients with HFpEF. Furthermore, we explored their relationship with peak oxygen uptake (VO2peak).

Methods and results

Fifteen patients with HFpEF (age = 70 ± 8.3 years) were randomized to either: (i) HIIT (4 × 4 min, 85–90% peak heart rate, interspersed with 3 min of active recovery; n = 9) or (ii) MI‐ACT (30 min at 70% peak heart rate; n = 6). Patients were trained 3 days/week for 4 weeks and underwent VO2peak testing and 2D echocardiography at baseline and after completion of the 12 sessions of supervised exercise training. Left ventricular (LV) and right ventricular (RV) average global peak systolic longitudinal strain (GLS) and peak systolic longitudinal strain rate (GSR) were quantified. Paired t‐tests were used to examine within‐group differences and unpaired t‐tests used for between‐group differences (α = 0.05). Right ventricular average global peak systolic longitudinal strain improved significantly in the HIIT group after training (pre = −18.4 ± 3.2%, post = −21.4 ± 1.7%; P = 0.02) while RV‐GSR, LV‐GLS, and LV‐GSR did not (P > 0.2). No significant improvements were observed following MI‐ACT. No significant between‐group differences were observed for any strain measure. ΔLV‐GLS and ΔRV‐GLS were modestly correlated with ΔVO2peak (r = −0.48 and r = −0.45; P = 0.1, respectively).

Conclusions

In patients with HFpEF, 4 weeks of HIIT significantly improved RV‐GLS.
Malonic Acid Derivatives on Duty as Electron‐Withdrawing Units in Push–Pull Molecules
Authors: Klikar Milan , Jelínková Veronika , Růžičková Zdeňka , Mikysek Tomáš , Pytela Oldřich , Ludwig Miroslav , Bureš Filip
Published: March 2017

Based on the 2‐(N‐piperidinyl)thiophene central donor, 32 model push–pull molecules with systematically varied malonic acid‐derived peripheral acceptors have been prepared. Further property tuning has been achieved by modifying the π‐linker and the structural arrangement (linear vs. quadrupolar D–π–A systems). Malonic acid derivatives such as cyanoacetic acid, malondinitrile, diethyl malonate, Meldrum′s acid, and N,N′‐dibutyl(thio)barbituric acid as well as 1,3‐diketo analogues dimedone and indan‐1,3‐dione were employed as acceptor moieties. Knoevenagel condensation with four thiophene aldehydes afforded the target chromophores in satisfactory yields. The electron‐withdrawing abilities of malonic acid acceptors were examined both by experiment including X‐ray analysis, differential scanning calorimetry, electrochemistry, and UV/Vis absorption spectroscopy, and by DFT calculations. Details of the structure–property relationships have been elucidated. According to the increasing electron‐withdrawing ability, the widely used malonic acid acceptor units can be ordered: diethyl malonate ≤ cyanoacetic acid < malondinitrile < Meldrum's acid < dimedone ≤ N,N′‐dibutylbarbituric acid < indan‐1,3‐dione ≤ N,N′‐dibutylthiobarbituric acid.
Multicomponent Reactions of Arylglyoxal, 4‐Hydroxycoumarin, and Cyclic 1,3‐C,N‐Binucleophiles: Binucleophile‐Directed Synthesis of Fused Five‐ and Six‐Membered N‐Heterocycles
Authors: Mishra Richa , Panday Anoop Kumar , Choudhury Lokman H. , Pal Jagannath , Subramanian Ranga , Verma Ajay
Published: March 2017

The multicomponent reaction (MCR) of arylglyoxal, 4‐hydroxycoumarin, and various cyclic 1,3‐C,N‐binucleophiles in acetic acid under microwave conditions provides fused five‐ or six‐ membered N‐heterocycles depending on the ring size of the binucleophiles. 1,3‐C,N‐binucleophiles, such as amino‐pyrazole/oxazole, that have a five‐membered ring provide fused six‐membered dihydropyridines or pyridine derivatives, whereas aminouracil, cytosine, and 4/3‐aminocoumarines that have a six‐membered ring provide the corresponding five‐membered fused pyrroles. By using DFT calculations, the mechanism of the ring‐size‐dependent multicomponent cyclization reaction is explained. Cyclic 1,3‐C,N‐binucleophiles, such as aminopyrazole, aminooxazole, aminocoumarin, aminouracil, and cytosine, were explored in this MCR, and the corresponding fused pyrroles/dihydropyridines or pyridines were obtained in very good yields. The structures of the fused molecules were unambiguously confirmed by spectroscopic techniques and single‐crystal X‐ray analysis.
Local disruption or global condition? El Niño as weather and as climate phenomenon
Authors: Höhler Sabine
Published: March 2017

El Niño denotes a periodical warm water stream in the Pacific Ocean. But who knew about this phenomenon, where and how? El Niño ‘the boy’ emerged as a fabric of local experiences and stories of extreme weather events: tropical winter storms, floods, droughts and famines in the coastal states of South America, Indonesia and Southeast Asia. In the Northern Hemisphere this rich cultural history went largely unnoticed. Only in the 1980s and 1990s did El Niño acquire global recognition as an effect of the oceanic and atmospheric currents in the tropical Pacific region. As the oceans moved from a marginal to a central position in the discourse on the Earth's climate cycles, ENSO – the ‘El Niño Southern Oscillation’ – became part of a global climate pattern. This paper explores El Niño ‘the boy’ and ENSO El Niño Southern Oscillation as juxtaposed and superposed environmental perceptions. While El Niño the boy conveyed horrific weather experiences on the human scale, ENSO became known through terrific scientific views of Earth from space. Earth observation by remote sensing satellites collected vast arrays of local measurements into new data fabrics. Studying the case of the US–French orbital satellite mission of TOPEX/Poseidon, this paper examines both the imagery from satellite data and the forecasting efforts preceding the strong El Niño winter of 1997–8. From the data and image sets of remote sensing satellites, recurring local disruptions emerged as a periodic global climate condition. Local experiences of El Niño and scientific perceptions of ENSO as a global climate cycle did not translate easily into each other. The paper discusses some of the epistemological tensions across spatial scales. While El Niño's shift from exception to regularity fed into the framing of ‘climate change’ as a global disaster, the emerging ENSO regime obscured disaster locally.
Are rare variants really independent?
Authors: Turkmen Asuman , Lin Shili
Published: March 2017

Recent advances in genotyping with high‐density markers allow researchers access to genomic variants including rare ones. Linkage disequilibrium (LD) is widely used to provide insight into evolutionary history. It is also the basis for association mapping in humans and other species. Better understanding of the genomic LD structure may lead to better‐informed statistical tests that can improve the power of association studies. Although rare variant associations with common diseases (RVCD) have been extensively studied recently, there is very limited understanding, and even controversial view of LD structures among rare variants and between rare and common variants. In fact, many popular RVCD tests make the assumptions that rare variants are independent. In this report, we show that two commonly used LD measures are not capable of detecting LD when rare variants are involved. We present this argument from two perspectives, both the LD measures themselves and the computational issues associated with them. To address these issues, we propose an alternative LD measure, the polychoric correlation, that was originally designed for detecting associations among categorical variables. Using simulated as well as the 1000 Genomes data, we explore the performances of LD measures in detail and discuss their implications in association studies.
Coercion and Access to Health Care
Authors: Reiter Keramet
Published: March 2017

In this issue of the Hastings Center Report, Paul Christopher and colleagues describe a study of why prisoners choose to enroll in clinical research. The article represents an important methodological and policy contribution to the literature on prisoner participation in research and medical experimentation. Given the methodological and ethical debates to which this research seeks to make an empirical contribution, the careful manner in which the study was conducted and the transparency with which the authors describe the research is especially noteworthy. In sum, I respect the research steps the authors took. However, I disagree with their conclusions about both the absence of coercion for prisoner clinical research participants and the merits of applying risk‐benefit models to govern prisoner research participation.
Justifying Clinical Nudges
Authors: Gorin Moti , Joffe Steven , Dickert Neal , Halpern Scott
Published: March 2017

The shift away from paternalistic decision‐making and toward patient‐centered, shared decision‐making has stemmed from the recognition that in order to practice medicine ethically, health care professionals must take seriously the values and preferences of their patients. At the same time, there is growing recognition that minor and seemingly irrelevant features of how choices are presented can substantially influence the decisions people make. Behavioral economists have identified striking ways in which trivial differences in the presentation of options can powerfully and predictably affect people's choices. Choice‐affecting features of the decision environment that do not restrict the range of choices or significantly alter the incentives have come to be known as “nudges.”

Although some have criticized conscious efforts to influence choice, we believe that clinical nudges may often be morally justified. The most straightforward justification for nudge interventions is that they help people bypass their cognitive limitations—for example, the tendency to choose the first option presented even when that option is not the best for them—thereby allowing people to make choices that best align with their rational preferences or deeply held values. However, we argue that this justification is problematic. We argue that, if physicians wish to use nudges to shape their patients’ choices, the justification for doing so must appeal to an ethical and professional standard, not to patients’ preferences. We demonstrate how a standard with which clinicians and bioethicists already are quite familiar—the best‐interest standard—offers a robust justification for the use of nudges.
Expression of AKR1B10 as an independent marker for poor prognosis in human oral squamous cell carcinoma
Authors: Ko Hui‐Hsin , Cheng Shih‐Lung , Lee Jang‐Jaer , Chen Hsin‐Ming , Kuo Mark Yen‐Ping , Cheng Shih‐Jung
Published: March 2017

Background

Aldo‐keto reductase family 1 member B10 (AKR1B10) is implicated in xenobiotic detoxification and has disparate functions in tumorigenesis that are dependent on the cell types. The purpose of this study was to investigate the clinicopathological significance of AKR1B10 as a prognostic marker for oral squamous cell carcinomas (OSCCs).

Methods

AKR1B10 protein expression was analyzed by immunohistochemistry in 77 patients with OSCC.

Results

The AKR1B10 labeling score for OSCCs (1.16 ± 1.14) was significantly higher than that for normal oral mucosa (0.10 ± 0.23; p < .0001). High expression of AKR1B10 significantly correlated with large tumor size (p = .041), advanced TNM classification (p = .037), and patient's areca quid chewing habit (p = .025). Multivariate analysis revealed that high AKR1B10 labeling score >1.16 (hazard ratio, 3.647; p = .001) significantly correlated with mortality.

Conclusion

AKR1B10 overexpression is an independent poor prognostic biomarker for OSCC. AKR1B10 inhibitors may be promising in clinical trials against OSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1327–1332, 2017
Narratives of effort among Chinese, Hungarian and Chinese immigrant students in Hungary
Authors: Sebestyén Nóra , Ivaskevics Krisztián , Fülöp Márta
Published: March 2017

The present study aimed to reveal the effect of migration processes on the conceptualisation of effort involving two cultures with different approaches towards effort: China with an effort‐promoting mindset and Hungary with an effort‐repressing mindset. In the study, narrative approach was used in cross‐sectional design involving Chinese, Hungarian and Chinese immigrant students living in Hungary. Altogether 139 students—49 Hungarian, 47 Chinese, 43 Chinese immigrants—aged 13–15 years provided narratives on past personal effort. Content analyses were done on 222 narratives. The results showed that the Chinese narratives of effort were characterised by learning and achievement orientation with elaborated effort process. In contrast, the Hungarian narratives were characterised by relationship orientation and emotional coping with a non‐elaborated effort process. The narratives of the Chinese immigrants showed great similarity to those of the Chinese students reflecting academic effort, achievement goals and elaborated process. The findings suggest that the traditional Chinese approach towards effort persists in cultural transition, and academic effort tends to be a primary resource for educational success for the Chinese immigrant students in Hungary.
The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children
Authors: Fu Wen , Liu Guo‐Chang , Zhao Zhang , Zhu Jinhong , Jia Wei , Zhu Shi‐Bo , Hu Jin‐Hua , Wang Feng‐Hua , He Jing , Xia Huimin
Published: March 2017

Background

Wilms tumor (WT) is the most common urologic cancer in children. However, genetic bases underlying WT remain largely unknown. Previous studies indicated that Lin28 homolog B (LIN28B) level is significantly elevated in some WTs. Enforced expression of Lin28b during kidney development could induce WT. Genetic variations in the LIN28B gene may be related to WT susceptibility.

Method

In this study, we aimed to assess the association between LIN28B gene polymorphisms and WT susceptibility in Chinese children. Four potentially functional polymorphisms in the LIN28B gene (rs314276 C>A, rs221634 A>T, rs221635 T>C and rs9404590 T>G) were genotyped in 145 cases and 531 cancer‐free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.

Results

Our results showed that the rs314276 CA genotype was associated with a decreased WT risk (CA vs CC: adjusted OR=0.65, 95% CI=0.43‐0.98, P=.042). Moreover, we found that carriers of the 1‐3 risk genotypes had a significantly increased WT risk when compared to the non‐carriers (adjusted OR=1.51, 95% CI=1.03‐2.20, P=.035). The association with risk genotypes was more predominant in children 18 month old or younger and in females.

Conclusion

In summary, these results indicated that the LIN28B gene rs314276 C>A polymorphism alone and three combined polymorphisms may be able to modify WT susceptibility in Southern Chinese children. Our findings call for further validation in large studies with different ethnicities involved.
Depressive Symptoms and the Anticipation and Experience of Uplifting Events in Everyday Life
Authors: Starr Lisa R. , Hershenberg Rachel
Published: March 2017

Objective

Despite proliferation of laboratory‐based studies examining reward functioning in depression, few studies have examined these processes in everyday life. We addressed this shortcoming by exploring experience and anticipation of uplifting experiences under ecologically valid conditions

Method

One hundred fifty‐seven young adults, oversampled for depressive symptoms, completed a 14‐day diary tracking mood in relation to recent and anticipated positive events

Results

Consistent with studies supporting “mood‐brightening” effects in depression, participants with greater baseline dysphoria showed stronger associations between elevated daily uplifts and lower daily depressive symptoms, particularly when events were interpersonal in nature. Baseline dysphoria was associated with lower daily anticipation of positive next‐day experiences; however, when dysphoric individuals did anticipate positive experiences, they experienced greater reductions in depressed mood

Conclusion

Results suggest that despite reward processing deficits found in laboratory studies, dysphoric individuals show improvements in mood in conjunction with anticipation and consumption of uplifting events in daily life.
Comparison of MR flow quantification in peripheral and main pulmonary arteries in patients after right ventricular outflow tract surgery: A retrospective study
Authors: Rutz Tobias , Meierhofer Christian , Naumann Susanne , Martinoff Stefan , Ewert Peter , Stern Heiko C. , Fratz Sohrab
Published: March 2017

Purpose

To compare the quantification of pulmonary stroke volume (SV) by phase contrast magnetic resonance (PC‐MR) in the main pulmonary artery (MPA) to the sum of SVs in both peripheral pulmonary arteries (PPA) in different right ventricular (RV) outflow pathologies.

Materials and Methods

Pulmonary SV was determined by PC‐MR in the MPA and the PPA in healthy individuals (H, n = 54), patients after correction for tetralogy of Fallot with significant pulmonary regurgitation and without pulmonary or RV outflow tract stenosis (PR, n = 50), and in patients with RV outflow tract or pulmonary valve stenosis (PS, n = 50). Resulting SVs were compared to aortic SV in the ascending aorta.

Results

Mean age was similar between the groups: H 28 ± 17 vs. PR 24 ± 11 vs. PS 22 ± 10 years. Bland–Altman analyses revealed in all groups a relatively small systemic (bias) but large random error (limits of agreement) for pulmonary SV determined in the MPA as compared to summed SVs in the PPA. The largest limits of agreement were present in PS patients: H: MPA 3.9% (–11, + 19) vs. PPA 0.4% (–15, + 15); PR: MPA 5.2% (–25, + 36) vs. PPA 0.6% (–24, + 26); PS: MPA 5% (–36; + 46), PPA –0.03% (–34, + 35).

Conclusion

The accuracy of PC‐MR in the MPA is reasonable; however, a large random error (precision) is observed that is most pronounced in PS patients. This potential error should be taken into consideration when interpreting MPA flow measurements.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017;46:1839–1845.
DWI of the prostate: Comparison of a faster diagonal acquisition to standard three‐scan trace acquisition
Authors: Corcuera‐Solano Idoia , Wagner Mathilde , Hectors Stefanie , Lewis Sara , Titelbaum Nicholas , Stemmer Alto , Rastinehad Ardeshir , Tewari Ashutosh , Taouli Bachir
Published: March 2017

Purpose

To compare a faster diagonal diffusion‐weighted imaging (d‐DWI) to conventional three‐scan trace DWI (t‐DWI) acquisition for prostate magnetic resonance imaging (MRI) in terms of image quality, tumor detection/conspicuity, Prostate Imaging Reporting and Data System (PI‐RADS) characterization, quantitative estimated signal‐to‐noise ratio (eSNR), and apparent diffusion coefficient (ADC) measurement.

Patients and Methods

A total of 34 consecutive men with suspected prostate cancer (PCa) who underwent 3T MRI of the prostate were assessed. MRI included t‐DWI and d‐DWI (using b‐values of 50, 1000, and 1600 s/mm2, number of averages 1/5/10 for t‐DWI vs. 2/8/14 for d‐DWI, acquisition time 6:21 min vs. 4:17 min, respectively). Two independent observers evaluated image quality, including image sharpness, anatomic distortion, and artifacts on a 5‐point scale (1–5) and assessed tumor detection, conspicuity, and PI‐RADS classification with both DWI sequences. eSNR and ADC were measured in the peripheral zone (PZ), transitional zone (TZ), and detected tumors. Data was compared using paired Wilcoxon signed rank tests and McNemar test. Coefficients of variations (CV) between ADC obtained with both sequences were calculated.

Results

Significantly fewer artifacts were observed on d‐DWI at b 1600 for observer 2 (P < 0.01), while the other image quality scores were equivalent for both sequences. eSNR was lower with d‐DWI vs. t‐DWI in PZ and TZ for b 1000 (P < 0.01 and P = 0.03, respectively) and b 1600 (P < 0.01 for both). ADC reproducibility between sequences was excellent (CV <10%). No significant differences were found for tumor detection (P ≥ 0.25), conspicuity (P ≥ 0.12), or PI‐RADS classification (P ≥ 0.10).

Conclusion

d‐DWI can provide a substantial reduction in acquisition time (∼30%) while maintaining equivalent tumor detection, PI‐RADS score, image quality, and ADC values.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017;46:1767–1775.
Effect of mechanical stresses on graphene‐based devices
Authors: Zheng Yi , Valerio Guido , Ren Zhuoxiang
Published: March 2017

In this work, we analyse the effect of mechanical stresses on graphene devices for application in flexible electronics. The possible Schottky contacts in the transistor are modeled through suitable transmission coefficients describing the tunnelling through the electrostatic potential along the graphene channel. The surface potential is determined by imposing an equality between the charges computed with a micromodel and a macromodel. All these computation tools are explicitly dependent on the choice of geometrical parameters, thus allowing the description of uniform geometrical deformations due to strains along a given direction. Numerical results are computed and discussed.
Hearing loss as a risk factor for dementia: A systematic review
Authors: Thomson Rhett S. , Auduong Priscilla , Miller Alexander T. , Gurgel Richard K.
Published: March 2017

Objectives

To review evidence of hearing loss as a risk factor for dementia.

Data Sources: PubMed

Review methods: A systematic review was conducted using the PubMed database using the search terms (hearing loss OR presbycusis) AND (dementia OR cognitive decline). Initially, 488 articles were obtained. Only those studies evaluating an association between hearing loss and incident dementia or cognitive decline were included in the analysis. This resulted in 17 articles which were thoroughly evaluated with consideration for study design, method for determining hearing loss and cognitive status, relevant covariates and confounding factors, and key findings.

Results

All of the 17 articles meeting inclusion criteria indicate that hearing loss is associated with dementia or cognitive decline. The methods used among the studies for ascertaining hearing loss and dementia were notably varied. For hearing loss, peripheral auditory function was tested far more than central auditory function. For peripheral audition, pure tone audiometry was the most commonly reported method for defining hearing loss. Only a few studies measured central auditory function by using the Synthetic Sentence Identification with Ipsilateral Competing Message test (SSI‐ICM) and the Staggered Spondaic Word Test (SSW). Dementia was most often defined using the Mini Mental State Exam (MMSE). However, many studies used extensive batteries of tests to define cognitive status, often including a neuropsychologist. Confounding variables such as cardiovascular risk factors were measured in 17 studies and family history of dementia was only evaluated in 1 study. Overall, the methods used by studies to ascertain hearing loss, cognitive status and other variables are valid, making their evaluation appear reliable.

Conclusion

While each of the studies included in this study utilized slightly different methods for evaluating participants, each of them demonstrated that hearing loss is associated with higher incidence of dementia in older adults.

Level of Evidence

Level V, systematic review.
Bi‐allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer
Authors: Mutter Robert W , Riaz Nadeem , Ng Charlotte KY , Delsite Rob , Piscuoglio Salvatore , Edelweiss Marcia , Martelotto Luciano G , Sakr Rita A , King Tari A , Giri Dilip D , Drobnjak Maria , Brogi Edi , Bindra Ranjit , Bernheim Giana , Lim Raymond S , Blecua Pedro , Desrichard Alexis , Higginson Dan , Towers Russell , Jiang Ruomu , Lee William , Weigelt Britta , Reis‐Filho Jorge S , Powell Simon N
Published: March 2017

Homologous recombination (HR) DNA repair‐deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51‐based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole‐exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large‐scale state transitions and specific mutational signatures. Somatic and/or germline genetic alterations resulting in bi‐allelic loss‐of‐function of HR genes underpinned functional HRD in 89% of cases, and were observed in only one of the 15 HR‐proficient samples tested. These findings indicate the importance of a comprehensive genetic assessment of bi‐allelic alterations in the HR pathway to deliver a precision medicine‐based approach to select patients for therapies targeting tumour‐specific DNA repair defects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bone morphogenetic protein and Notch signalling crosstalk in poor‐prognosis, mesenchymal‐subtype colorectal cancer
Authors: Irshad Shazia , Bansal Mukesh , Guarnieri Paolo , Davis Hayley , Al Haj Zen Ayman , Baran Brygida , Pinna Claudia Maria Assunta , Rahman Haseeb , Biswas Sujata , Bardella Chiara , Jeffery Rosemary , Wang Lai Mun , East James Edward , Tomlinson Ian , Lewis Annabelle , Leedham Simon John
Published: March 2017

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context‐dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ‐secretase‐independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co‐localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal‐subtype tumours, where it interacts with Notch to induce an epithelial–mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP–Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal‐subtype tumours promotes a synergistic BMP–Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal‐subtype CRC insensitive to γ‐secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Ethanol Extract of Pinus koraiensis Leaf Ameliorates Alcoholic Fatty Liver via the Activation of LKB1–AMPK Signaling In Vitro and In Vivo
Authors: Hong Sang‐Hyuk , Lee Hyemin , Lee Hyo‐Jung , Kim Bonglee , Nam Min‐Ho , Shim Bum‐Sang , Kim Sung‐Hoon
Published: March 2017

Although Pinus koraiensis leaf (PKL) was reported for its anti‐diabetes, anti‐obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP‐activated protein kinase signaling, low‐density lipoprotein receptor and decreased fatty acid biosynthesis‐related proteins such as sterol regulatory element‐binding protein 1c, fatty acid synthase, 3‐hydroxy‐3‐methylglutaryl‐CoA reductase in HepG2 cells. In SD rats with 25% alcohol‐induced fatty liver, PKL suppressed the levels of aspartate aminotransferase and triglyceride and also enhanced the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione s‐transferase compared with untreated control. Furthermore, PKL increased serum alcohol dehydrogenase and serum aldehyde dehydrogenase, but decreased serum alcohol concentration in ICR mice after alcohol administration. Consistently, histochemical analysis revealed that PKL attenuated alcohol‐induced fatty liver in SD rats. Overall, these findings suggest that PKL ameliorates alcohol‐induced fatty liver via activation of LKB1–AMP‐activated protein kinase and modulation of proteins related to lipogenesis synthesis, cholesterol synthesis and fatty acid oxidation. Copyright © 2017 John Wiley & Sons, Ltd.
Decentralized summation‐based triggering mechanism for Lipschitz nonlinear systems
Authors: Mousavi Seyed Hossein , Marquez Horacio J.
Published: March 2017

In this paper, a decentralized event‐based triggering mechanism for a class of nonlinear control systems is studied. It is assumed that the measurement sensors are geographically distributed and so local event generator modules are employed. Then, a novel periodic triggering condition is proposed for each module, which can potentially reduce the information exchange between subsystems compared with traditional control approaches, while maintaining closed‐loop asymptotic stability. The triggering condition parameters are designed through a convex optimization problem with LMI constraints. Finally, simulations are carried out to illustrate the performance of the introduced scheme. Copyright © 2017 John Wiley & Sons, Ltd.
Waterscape: a perspective for understanding the contested geography of water
Authors: Karpouzoglou Timothy , Vij Sumit
Published: March 2017

The waterscape is a perspective that has captured the imagination of diverse scholars interested in the interaction of water and society. This includes the way water travels in time and space and is shaped by culture and geography. In this article, we pay particular attention to the study of the waterscape in the political ecology tradition. Scholars following this tradition have placed strong emphasis on understanding the role of power and the contested nature of water in diverse rural, urban, and periurban landscapes. The article provides a brief account of the main strands of literature and serves the purpose of an introductory overview of the waterscape for beginners. We focus both on major works that have helped define the waterscape as a perspective in political ecology and recent studies on the role of unequal power and gender relationships, informal water practices, and local water flows such as ponds and wastewater. WIREs Water 2017, 4:e1210. doi: 10.1002/wat2.1210

This article is categorized under:

Engineering Water > Planning Water

Human Water > Water Governance

Human Water > Water as Imagined and Represented
A Selenium‐Nitrogen Chain with Selenium in Different Oxidation States
Authors: Karhu Aino J. , Jämsä Juho , Rautiainen J. Mikko , Oilunkaniemi Raija , Chivers Tristram , Laitinen Risto S.
Published: March 2017

The reaction of tBuNH2 with a mixture of SeCl2 and SeOCl2 in a 6:2:1 molar ratio produces the novel selenium‐nitrogen chain ClSeN(tBu)Se(O)Cl (4), in which the selenium atoms are in two different oxidation states, SeII and SeIV. The crystal structure of 4 is compared with that of the related SeII/SeII system ClSeN(tBu)SeCl (1) and differences are attributed to hyperconjugative effects. The energetics of the formation of 4 via two different routes are elucidated by PBE0/def2‐TZVPP calculations.
Plutarch'sLivesin the Byzantine chronographic tradition: the chronicle of John Zonaras
Authors: Kampianaki Theofili
Published: March 2017

This article focuses on the presence of material from Plutarch'sLivesin Byzantine chronicles, particularly that of John Zonaras, the only chronicler to draw heavily on Plutarch's biographies. Zonaras’ strong appreciation of Plutarch is evident when he repeatedly digresses from the main narrative to incorporate Plutarchean material related to secondary topics. His method of selection from Plutarch's RomanLivesis governed by particular principles: Zonaras’ individual literary tastes, as well as those of his contemporary audience, and the adaptation of Plutarch's material to the Byzantine social and cultural context. These considerations reveal Zonaras to be not merely a copyist of earlier writings, but instead a compiler with his own authorial agenda.
The beard and its philosopher: Theodore Prodromos on the philosopher's beard in Byzantium
Authors: Kucharski Janek , Marciniak Przemysław
Published: March 2017

The following paper analyses Theodore Prodromos’ satire,Against the old man with a long beard. It argues that the text which is heavily based on the ancient tradition of ridiculing philosophers is in fact directed against the twelfth-century fellow teachers of Prodromos.
Separating the Wheat from the Chaff: Dating Charred Plant Remains Extracted from Daub (With Reference to the 14C Chronology of the Epi-Lengyel Culture in Upper Silesia)
Authors: Chmielewski Tomasz J , Sady Agata , Goslar Tomasz , Furmanek Mirosław , Juchelka Jiři
Published: March 2017

Despite their great potential, charred particles of chaff-and-straw temper from daub architecture have very rarely been considered as material suitable for 14C dating. This short paper is intended to change this situation. With this aim in mind, we first present the rationale and objectives of the sampling procedure based on archaeobotanical exploration of prehistoric remains of daub architecture, and then report and discuss the results of a short chronometric exercise based on such samples. The empirical verification of the sampling procedure was based on finds related to the epi-Lengyel culture from Upper Silesia.
AESCHINES ΚΟΙΤΟΦΟΡΟΣ (DEM. 18.260)
Authors: Olson S. Douglas
Published: March 2017

According to the manuscripts of On the Crown (18.260), Demosthenes mockingly claims that, as the youthful Aeschines led processions in his mother's mystery-cult celebrations, he was hailed by various old women as ἔξαρχος καὶ προηγεμὼν καὶ κιττοφόρος καὶ λικνοφόρος καὶ τοιαῦθ’ (‘leader and guide and ivy-bearer and bearer-of-the-winnowing-fan and the like’). Τhese are clearly special titles—Aeschines is not just one celebrant among many but a leading figure in the train of worshippers—and recent editors accordingly note that κιττοφόρος seems weak and follow Albert Rubens (‘Rubenius’) in printing instead κιστοφόρος (‘basket-bearer’), which Harpocration reports was read by some authorities here. κιστοφόρος appears to be supported by ΣF2 18.260 (296 Dilts) ὁ φέρων τὰς κίστας (‘the man who carries the baskets’), which is easily taken to confirm that Demosthenes meant that Aeschines stood out in the crowd of celebrants inter alia because he carried containers within which must have been sacred implements of some sort.
ὌΡΧΙΣ: TESTICLE, TESTICULATE AND GLANS PENIS
Authors: Cotter Joseph
Published: March 2017

Goffredo Coppola, the Italian editor of this papyrus, supposed that τὸν ὄρχιν (the testicle) = τοὺς ὄρχεις; but he was puzzled when no likely erotic word seemed available to finish the line. He suggested φαλ[ῆς, from φαλός = λευκός (‘white’) to be followed by some metaphorical word for penis such as κέρκου. Romagnoli noted that it made no sense to have the testicle(s) dependent on the penis, and argued that Hipponax here intended ὄρχις to refer metaphorically to the glans penis; therefore, he emended to καί μοι τὸν ὄρχιν τῆς φαλ[ῆς ἐκλέψασα (= peeling back the penis’ foreskin); but his feminine form τῆς φαλ[ῆς is unlikely given the masculine form τοῦ φάλεω in Hipponax fr. 21 W. Medeiros suggested ὄρχις, sing. = ὄσχη ‘scrotum’; West actually exalted the role of the testicle by emending to τῆς φαλ[άκρης ἕλκουσα ‘pulling my testicle by the bald spot’; but it is not obvious why hitting the testicles merits such attention in a narrative fixed on the failure to attain an erection.
RITES AND RELIGIOUS BELIEFS OF SOCRATES ACCORDING TO XENOPHON (APOLOGY OF SOCRATES11 ANDMEMORABILIA1.1.2)
Authors: Jakubiec Alexandre
Published: March 2017

Two excerpts from Xenophon, in which he states that Socrates avidly practised religious ceremonies promoted by Athens, are subject to two different interpretations by modern historians. For some, they are the proof that the Athenian city was only concerned with the rituals of its fellow citizens, and in no way with their beliefs. In contrast with this view, Hendrick Versnel feels that, by writing that Socrates performed ceremonies, Xenophon thinks that he proves that his master really did believe in the gods. Both of these interpretations are incorrect, as a careful new consideration of these passages can demonstrate.