bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate generalized hyperbolic laws for modeling financial log‐returns: Empirical and theoretical considerations
Authors: Fotopoulos Stergios B. , Paparas Alex , Jandhyala Venkata K.
Published: March 2020

The aim of this study is to consider the multivariate generalized hyperbolic (MGH) distribution for modeling financial log‐returns. Beginning with the multivariate geometric subordinated Brownian motion for asset prices, we first demonstrate that the mean‐variance mixing model of the multivariate normal law is natural for log‐returns of financial assets. This multivariate mean‐variance mixing model forms the basis for deriving the MGH family as a class of distributions for modeling the behavior of log‐returns. While theory suggests MGH to be an appropriate family, empirical considerations must also support such a proposition. This article reviews various empirical criteria in support of the MGH family. From a theoretical perspective, we present an alternative form of the density for the MGH family. This alternative density for the MGH family is more convenient for deriving certain limiting results. Numerical study on the distributional behavior of six stocks from the US market forms the foundation of investigating the suitability of the MGH family and some of its well‐known subfamilies. Along the way, we implement the multicycle expectation conditional maximization algorithm for estimating the parameters of the MGH family. Then adapting a recently developed algorithmic procedure, we develop a self‐contained methodology for carrying out goodness‐of‐fit tests for the MGH distribution. The numerical study on the six stocks confirms the suitability of the MGH distribution for different time scales of the log‐returns such as daily, monthly, and 6‐monthly data.
Optimizing Ni−Fe−Ga alloys into Ni2FeGa for the Hydrogenation of CO2 into Methanol
Authors: Smitshuysen Thomas E. L. , Nielsen Monia R. , Pruessmann Tim , Zimina Anna , Sheppard Thomas L. , Grunwaldt Jan‐Dierk , Chorkendorff Ib , Damsgaard Christian D.
Published: March 2020

A screening study of the catalytic performance of ternary alloy nanoparticles containing nickel, iron and gallium supported on silica for methanol synthesis from CO2 and H2 was performed. Catalysts were prepared by incipient wetness impregnation and subsequently reduced in H2 before catalytic testing. Ni2FeGa showed the best performance of the tested catalysts in terms of methanol yield. An optimization of the preparation was done to improve activity and selectivity, reaching a performance close to that of commercially available Cu/ZnO/Al2O3/MgO at low reaction temperatures and pressure. Extensive in situ characterisation using environmental TEM, in situ XRD and in situ EXAFS of the formation of the Ni2FeGa catalyst explains an optimal reduction temperature of 550 °C: warm enough that the three atomic species will form an alloy while cold enough to prevent the catalyst from sintering during the formation.
Model‐Based Optimization of Ripening Processes with Feedback Modules
Authors: Spinola Michele , Keimer Alexander , Segets Doris , Leugering Günter , Pflug Lukas
Published: March 2020

In order to obtain high‐quality particulate products with tailored properties, process conditions and their evolution in time must be chosen appropriately. Although the efficiency of these products depends on their dispersity in several dimensions, in established processes the particle size is usually the decisive variable to adjust. As part of the synthesis of these products, feedback modules are often incorporated so that a time‐dependent ratio of the obtained product can flow back into the system. Moreover, the synthesis should be an energy‐ and resource‐efficient process. To provide a means of ensuring this requirement, a model‐ and gradient‐based, numerically efficient optimization tool for particle synthesis is presented which was developed to describe population balance equations incorporating feedback terms.
Fullerene C76: An Unexplored Superior Electrode Material with Wide Operating Potential Window for High‐Performance Supercapacitors
Authors: Ali Basant A. , Biby Ahmed H. , Allam Nageh K.
Published: March 2020

Carbon materials have widely been used to enhance the performance of a plethora of supercapacitor electrode materials. In this regard, it is crucial to identify carbon materials that function over a wide pH range while enjoying a wide potential window. Herein, the DFT calculations were used to elucidate the electronic performance of C76and the C76/electrolyte interface. The electronic investigation revealed the nature of the conductivity and charge storage mechanism of C76based on the bandgap and quantum capacitance calculations. Also, the electrochemical and electronic properties of fullerene C76have been extensively investigated over a wide pH range; acidic H2SO4, basic KOH, and neutral Na2SO4. The results showed a promising performance in the three electrolytes. Moreover, C76electrodes exhibited a potential window of 1.9 V in Na2SO4electrolyte, resulting in capacitances of 171 F/g and 142 F/g at a scan rate of 1 mV/s in the positive and negative potential windows, respectively. The material showed a pseudocapacitance performance of 65 % in Na2SO4electrolyte in the positive potential window. We believe higher fullerenes provide a new class of materials for developing versatile supercapacitor devices for efficient energy storage.
Low‐Temperature Solution Crystallization of Nanostructured Oxides and Thin Films
Authors: Bretos Iñigo , Diodati Stefano , Jiménez Ricardo , Tajoli Francesca , Ricote Jesús , Bragaggia Giulia , Franca Marina , Calzada Maria Lourdes , Gross Silvia
Published: March 2020

As an introduction to this themed issue, a critically selected overview of recent progress on the topic of solution methods for the low‐temperature crystallization of nanoscale oxide materials is presented. It is focused on the low‐temperature solution processing of oxide nanostructures and thin films. Benefits derived from these methods span from minimizing the environmental impact to reducing the fabrication costs. In addition, this topic is regarded as a key objective in the area because it offers a unique opportunity for the use of these materials in areas like flexible electronics, energy conversion and storage, environmental sciences, catalysis, or biomedicine.
CpTiCl2‐Catalyzed Cross‐Coupling between Internal Alkynes and Ketones: A Novel Concept in the Synthesis of Halogenated, Conjugated Dienes
Authors: Roldan‐Molina Esther , Nievas Maria M. , Navarro Jorge A. R. , Oltra J. Enrique
Published: March 2020

A novel concept for the synthesis of halogenated, conjugated dienes is disclosed: the CpTiCl2‐catalyzed coupling of keto‐alkynes, in the presence of Me3SiBr/Et3N⋅HBr. This reaction provided five‐, six‐, and seven‐membered carbocycles, nitrogenated heterocycles, as well as six‐membered oxygenated heterocycles leading to a brominated conjugate diene. These products showed high reactivity in the Diels–Alder, Suzuki, and Sonogashira reactions, giving complex chemical structures in only three steps from the corresponding acyclic keto‐alkyne. Hopefully, this strategy will pave the way towards the synthesis of bioactive natural products and new materials.
Ruthenium(II)‐Catalyzed Double Annulation of Quinones: Step‐Economical Access to Valuable Bioactive Compounds
Authors: da Silva Júnior Eufrânio N. , de Carvalho Renato L. , Almeida Renata G. , Rosa Luisa G. , Fantuzzi Felipe , Rogge Torben , Costa Pedro M. S. , Pessoa Claudia , Jacob Claus , Ackermann Lutz
Published: March 2020

Double ruthenium(II)‐catalyzed alkyne annulations of quinones were accomplished. Thus, a strategy is reported that provides step‐economical access to valuable quinones with a wide range of applications. C−H/N−H activations for alkyne annulations of naphthoquinones provided challenging polycyclic quinoidal compounds by forming four new bonds in one step. The singular power of the thus‐obtained compounds was reflected by their antileukemic activity.
Mind the gap: Gendered publication trends in oncology
Authors: Dalal Nicole H. , Chino Fumiko , Williamson Hannah , Beasley Georgia M. , Salama April K. S. , Palta Manisha
Published: March 2020

Background

Investigating scientific publication trends in the field of oncology may highlight opportunities for improved representation, mentorship, collaboration, and advancement for women.

Methods

We conducted a bibliometric analysis of Annals of Surgical Oncology; Cancer; International Journal of Radiation Oncology, Biology, Physics (IJROBP); JAMA Oncology; and Journal of Clinical Oncology in 1990, 2000, 2010, and 2017. Full name and degree credentials per author role (ie, first or senior author), article type, publication year, and citation metrics were collected. First names were used to identify author gender.

Results

Across 9189 articles, female representation rose between 1990 and 2017 (first authors: 17.7% in 1990, 36.6% in 2017; senior authors: 11.7% in 1990, 28.5% in 2017). For the 50 most cited articles per year, women comprised a smaller percent of first (26.5%) and senior (19.9%) authors. The average citation count was higher for male first (44.8 per article) and senior (47.1) authors compared to female first (39.7) and senior (44.1) authors. With male senior authors, the first author was more likely male (71.4% male; 25.0% female); with female senior authors, first authors were 50.2% male and 47.6% female. IJROBP had the lowest total female representation among first (25.1%) and senior (16.7%) authors. Women had more MDs with Masters degrees, whereas men held more MDs only and more MDs with PhDs.

Conclusion

Despite positive trends, substantial gendered differences in oncology publications persist. Fostering more women in oncology research will benefit female representation at many levels of academia and improve productivity, collaboration, and recruitment, especially in technical fields such as radiation and surgical oncology.
Forty‐year trends in menopausal hormone therapy use and breast cancer incidence among postmenopausal black and white women
Authors: Chlebowski Rowan T. , Aragaki Aaron K. , Anderson Garnet L. , Prentice Ross L.
Published: March 2020

After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age‐adjusted breast cancer incidence in more than 20 years was seen in 2003‐2004 among US women 50 years of age or older. Subsequent trends in breast cancer incidence have been described, but most reports have not focused on the postmenopausal age group or fully engaged the potential influence of reduced hormone therapy on breast cancer incidence trends by race/ethnicity. To address this gap, this commentary examines trends for annual age‐adjusted breast cancer incidence over a 40‐year period from 1975 to 2015 for white and black women on the basis of findings from the Surveillance, Epidemiology, and End Results 9 registries. Overall, the sharp decline in breast cancer incidence seen in 2003‐2004 was followed in the subsequent decade by a continued low breast cancer incidence plateau in white women that has largely persisted. In contrast, a new discordance between breast cancer incidence trends in black and white women has emerged. In the 2005‐2015 decade, a sustained increase in breast cancer incidence in black women has resulted in annual incidence rates comparable, for the first time, to those in white women. This commentary explores the hypothesis that the over‐decade‐long and discordant changes in breast cancer incidence rates in postmenopausal black and white women are, to a large extent, associated with changes in hormone therapy use in these 2 groups.
Computational modeling of braided‐stent deployment for interpreting the mechanism of stent flattening
Authors: Shiozaki Shunya , Otani Tomohiro , Fujimura Soichiro , Takao Hiroyuki , Wada Shigeo
Published: March 2020

This study develops a computational model of the braided stent for interpreting the mechanism of stent flattening during deployment into curved arteries. Stent wires are expressed using Kirchhoff's rod theory and their mechanical behavior is treated using a corotational beam formulation. The equation of motion of the braided stent is solved in a step‐by‐step manner using the resultant elastic force and mechanical interactions of wires with friction. Examples of braided‐stent deployment into idealized arteries with various curvatures are numerically simulated. In cases of low curvature, the braided stent expands from a catheter by releasing the bending energy stored in stent wires, while incomplete expansion is found at both stent ends (ie, the fish‐mouth phenomenon), where relatively little bending energy is stored. In cases of high curvature, much torsional energy is stored in stent wires locally in the midsection of the curvature and the bending energy for stent self‐expansion is not fully released even after deployment, leading to stent flattening. These findings suggest that the mechanical state of the braided stent and its transition during deployment play an important role in the underlying mechanism of stent flattening.

Novelty Statement

This study developed a computational mechanical model of the braided stent for interpreting stent flattening, which is a critical issue observed during deployment into highly curved arteries. Mechanical behaviors of the stent wires are appropriately treated by corotational beam element formulation with considering multiple contacts. We conducted numerical examples of the stent deployment into curved arteries and found that the mechanical state of the braided stent during deployment associated with occurrences of the stent flattening. We believe this finding gives new insight into the mechanism of stent flattening and would advance the design of the stent and its deployment protocol.
A Silyl Ether Based Fluorescent Probe for Rapid Monitoring of Endogenous Peroxynitrite Concentration and Imaging in Living Cells through Multicolor Emission
Authors: Zhuo Jiezhen , Gong Ke , Guo Yuxin , Lu Gonghao , Chi Haijun , Duan Yajun , Zhang Zhiqiang , Li Xue
Published: March 2020

The peroxynitrite ion (ONOO−) has important roles in many biological processes. We have developed a multicolor ONOO−‐sensing probe (SiONNOH) that undergoes deprotonation and desilylation processes, which result in several changes in the emission wavelengths. In response to different concentrations of ONOO−, the probe exhibits fluorescence changes from pink (595 nm at 2 eq. ONOO−) to green (540 nm at 6 eq. ONOO−) via orange (3 eq. ONOO−) and yellow (4 eq. ONOO−) under physiological conditions until no fluorescence signal is observed after ONOO− is completely eliminated by lipoic acid. The probe shows the high selectivity for ONOO− and the limit of detection is calculated to be 1.27 μM. Moreover, the probe shows the capacity to monitor the concentration ranges of ONOO− through multicolor fluorescence in living cells, which will greatly facilitate the rapid detection of ONOO− concentration ranges by the naked eye under a UV light without any precision instrumentation.
Recording of diagnoses in public primary oral health care in a retrospective longitudinal observational study in a Finnish town: Underrepresentation of periodontitis diagnoses
Authors: Kallio Jouko , Kauppila Timo , Suominen Lasse , Heikkinen Anna M.
Published: March 2020

Objectives

This study investigates which oral diagnoses public primary dental care dentists record.

Methods

An observational register‐based retrospective follow‐up study was performed in the public primary oral health care of a Finnish town after the dentists were advised to mark the diagnoses in their practices. The rate of recorded diagnoses resulting from visits to the public primary care dentists was studied. The assessed diagnoses were recorded with the 10th revision of the International Classification of Diseases. The distribution of diagnoses was recorded during a 2‐year follow‐up period.

Results

The most frequent diagnosis groups were dental caries (K02, 38.6%), other diseases of dental hard tissues (K03, 14.9%), diseases of pulp and periapical tissues (K04, 11.4%), periodontal diseases (K05, 9.7%), and different types of bone fractures (S02, 8.1%). Periodontitis was underrepresented.

Conclusions

In public primary oral health care, there may be difficulties in adequate recording of certain chronic diseases.
Sustainable Battery Materials from Biomass
Authors: Liedel Clemens
Published: March 2020

Sustainable sources of energy have been identified as a possible way out of today's oil dependency and are being rapidly developed. In contrast, storage of energy to a large extent still relies on heavy metals in batteries. Especially when built from biomass‐derived organics, organic batteries are promising alternatives and pave the way towards truly sustainable energy storage. First described in 2008, research on biomass‐derived electrodes has been taken up by a multitude of researchers worldwide. Nowadays, in principle, electrodes in batteries could be composed of all kinds of carbonized and noncarbonized biomass: On one hand, all kinds of (waste) biomass may be carbonized and used in anodes of lithium‐ or sodium‐ion batteries, cathodes in metal–sulfur or metal–oxygen batteries, or as conductive additives. On the other hand, a plethora of biomolecules, such as quinones, flavins, or carboxylates, contain redox‐active groups that can be used as redox‐active components in electrodes with very little chemical modification. Biomass‐based binders can replace toxic halogenated commercial binders to enable a truly sustainable future of energy storage devices. Besides the electrodes, electrolytes and separators may also be synthesized from biomass. In this Review, recent research progress in this rapidly emerging field is summarized with a focus on potentially fully biowaste‐derived batteries.
Survey on vehicular ad hoc networks clustering algorithms: Overview, taxonomy, challenges, and open research issues
Authors: Senouci Oussama , Harous Saad , Aliouat Zibouda
Published: March 2020

Vehicular ad hoc networks (VANETs) have recently attracted considerable attention owing to their wide range of applications. However, there are several challenges, such as mobility, routing, scalability, quality of services, and security. Clustering is an important control mechanism in high‐mobility networks and has been verified to be a promising approach in VANETs as well, as it ensures a basic level of network performance. Accordingly, several clustering algorithms have been proposed for these networks, and different protocols typically focus on various performance metrics. In this study, we provide a thorough review of clustering algorithms in VANETs. First, we present background material regarding the clustering process. Secondly, we propose a new taxonomy that categorizes clustering algorithms in VANETs based on different design aspects and provides a description of the algorithms in each category. Thirdly, an analysis of the algorithms in each category is provided according to various comparison metrics. Fourthly, we highlight the main challenges for each category and discuss some open research issues. Finally, we provide a general comparison of different clustering algorithms according to selected key parameters. Thus, this study provides a more thorough understanding of VANET clustering algorithms and the research trends in this area.
Compressed sensing channel estimation for STBC‐SM based hybrid MIMO‐OFDM system for visible light communication
Authors: B. Manur Vishwaraj , Ali Layak
Published: March 2020

This paper presents the idea of sparse channel estimation using compressed sensing (CS) method for space–time block coding (STBC), and spatially multiplexing (SM) derived hybrid multiple‐input multiple‐output (MIMO) Asymmetrically clipped optical‐orthogonal frequency division multiplexing (ACO‐OFDM) optical wireless communication system. This hybrid system accounts multiplexing gain of SM and diversity gain of STBC technique. We present a new variant of sparsity adaptive matching pursuit (SaMP) algorithm called dynamic step‐size SaMP (DSS‐SaMP) algorithm. It makes use of the inherent and implicit structure of SaMP, along with dynamic adaptivity of step‐size feature which is compatible with the energy of the input signal, thus the name dynamic step size. Existing CS‐based recovery algorithms like orthogonal matching pursuit, SaMP, adaptive step‐size SaMP, and proposed DSS‐SaMP were compared for hybrid MIMO‐ACO‐OFDM visible light communication system. The performance analysis is demonstrated through simulation results with respect to bit error rate, symbol error rate, mean square error, computational complexity, and peak‐to‐average power ratio. Simulation results show that the proposed technique gives improved performance and lesser computational complexity in comparison with conventional estimation algorithms.
The aptamer BC 007 for treatment of dilated cardiomyopathy: evaluation in Doberman Pinschers of efficacy and outcomes
Authors: Werner Sabine , Wallukat Gerd , Becker Niels‐Peter , Wenzel Katrin , Müller Johannes , Schimke Ingolf , Wess Gerhard
Published: March 2020

Aims

Aptamer BC 007, a 15‐mer single‐strand DNA oligonucleotide (5'‐GGTTGGTGTGGTTGG‐3'), was developed to neutralize functional autoantibodies that bind to the extracellular domains of G protein‐coupled receptors (GPCR‐AAB), leading to the modulation of receptor‐mediated signalling cascades that induce pathophysiological states. Among the GPCR‐AAB, there are those directed against the β1‐adrenergic receptor (β1‐AAB) that are highly present in patients with dilated cardiomyopathy (DCM) and are increasingly accepted as disease drivers.

Using Doberman Pinschers (DP) with DCM, which possess similarities with human DCM among these β1‐AAB positivity for that the disease‐driving role in DP DCM was demonstrated, the safety of BC 007, efficacy for neutralizing β1‐AAB, and the DP's outcome were investigated.

Methods and results

Fourteen client‐owned β1‐AAB‐positive DP with electrocardiographically and echocardiographically indicated DCM were treated with BC 007. For controlling, two groups were created: 14 β1‐AAB‐positive DP with DCM not treated with BC 007 (Control 1) and 14 DP with DCM closely matched to the BC 007‐treated DP (Control 2), retrospectively selected from the institutional database of DP. After treatment, DP were monitored both echocardiographically, and for β1‐AAB, and survival curves were calculated. Based on clinical and laboratory examination, no adverse effects associated with BC 007 treatment were observed during the study. Forty‐eight hours after treatment, the DP's blood was free of β1‐AAB, which led to a reduction or stabilization of left ventricular end‐systolic volume (ESVI) during β1‐AAB free time in 10 of the treated DP. In one DP, where β1‐AAB returned after 3 months and ESVI worsened again, a second BC 007 treatment after 9 months again cleared the blood from β1‐AAB and improved the ESVI. Compared with the controls, DP treated with BC 007 showed a significantly longer survival time [572 days, interquartile range (IQR) 442–840 days] vs. Control group 1 (266 days, IQR 97–438 days; logrank: P = 0.009) and Control group 2 (229 days, IQR 174–319 days; logrank: P = 0.012).

Conclusions

Treatment with BC 007 for β1‐AAB neutralization was safe, resulted in a long‐lasting reduction of β1‐AAB combined with improved cardiac function and prolonged the survival of DP with DCM. Using a natural large animal model of DCM considered superior to small animal models of immunization‐induced cardiomyopathy, combined with a study design comparable with clinical trials, we believe that our results provide the basis for optimism that treatment with BC 007 might also be effective in human patients with DCM.
The burden of non‐cardiac comorbidities and association with clinical outcomes in an acute heart failure trial – insights from ASCEND‐HF
Authors: Bhatt Ankeet S. , Ambrosy Andrew P. , Dunning Allison , DeVore Adam D. , Butler Javed , Reed Shelby , Voors Adriaan , Starling Randall , Armstrong Paul W. , Ezekowitz Justin A. , Metra Marco , Hernandez Adrian F. , O'Connor Christopher M. , Mentz Robert J.
Published: March 2020

Aims

Non‐cardiac comorbidities are highly prevalent in patients with heart failure (HF). Our objective was to define the association between non‐cardiac comorbidity burden and clinical outcomes, costs of care, and length of stay within a large randomized trial of acute HF patients.

Methods and results

Patients with complete medical history for the following comorbidities were included: diabetes mellitus, chronic obstructive pulmonary disease, chronic liver disease, history of cancer within the last 5 years, chronic renal disease (baseline serum creatinine >3.0 mg/mL), current smoking, alcohol abuse, depression, anaemia, peripheral arterial disease, and cerebrovascular disease. Patients were classified by overall burden of non‐cardiac comorbidities (0, 1, 2, 3, and 4+). Hierarchical generalized linear models were used to assess associations between comorbidity burden and 30‐day all‐cause death or HF hospitalization and 180‐day all‐cause death in addition to costs of care and length of stay. A total of 6945 patients were included in the final analysis. Mean comorbidity number was 2.2 (± 1.34). Patients with 4+ comorbidities had higher rates of 30‐day all‐cause death/HF hospitalization as compared with patients with no comorbidities [odds ratio (OR) 3.32, 95% confidence interval (CI) 1.61–6.84; P < 0.01]. Similar results were seen with respect to 180‐day death (OR 2.13, 95% CI 1.33–3.43; P < 0.01). Higher comorbidity burden was associated with higher 180‐day costs of care and length of
stay.

Conclusions

Higher comorbidity burden is associated with poor clinical outcomes, higher costs of care, and extended length of stay. Further studies are needed to define the impact of comorbidity management programmes on outcomes for HF patients.
Ru‐Catalyzed Sequential Dehydrogenative Friedlander Reaction/sp3 C–H Activation/Knovenagel Condensation in the Regioselective Synthesis of Chimanine B Analogues
Authors: Prameela Soda , Nawaz Khan Fazlur‐Rahman
Published: March 2020

Choline chloride (ChCl) based deep eutectic solvent (DES), facilitated the regioselective synthesis of (E)‐1‐(4‐phenyl‐2‐styrylquinolin‐3‐yl)ethan‐1‐one (4), and (E)‐3‐phenyl‐1‐(4‐phenyl‐2‐((E)‐styryl)quinolin‐3‐yl)prop‐2‐en‐1‐ones, (5) from the corresponding 2‐amino‐5‐chloro benzhydrol, (1) in one‐pot strategy. The 2‐methyl‐3‐acetylquinoline generated in situ from the 2‐amino‐5‐chloro benzhydrol, (1) and acetyl acetone, (2) via dehydrogenative Friedlander reaction in DES could enable subsequent regio‐selective C‐2 methyl group sp3 C–H activation and rapid alkenylation with alcohols, (3) to provide the desired (E)‐2‐styrylquinolin‐3‐yl)ethan‐1‐ones, 4 in short reaction time and high yields and purity. Likewise, through the simultaneous C‐2 and C‐3 sp3 C–H activation with aromatic alcohols, (3) the (E)‐2‐styrylquinolin‐3‐yl)prop‐2‐en‐1‐ones, (5) formation was carried out in DES in high yields and purity. The physicochemical properties viz., UV/Vis, and fluorescence studies of the synthesized compounds were investigated. The absorption and emission properties of these luminophores are attributable to the presence of auxochromes in the 6‐position of quinoline moiety, styryl‐functional group at the 2‐position, and the enone group at 3‐position.
Predicting the strength of urban-rural clines in a Mendelian polymorphism along a latitudinal gradient
Authors: Santangelo James S. , Thompson Ken A. , Cohan Beata , Syed Jibran , Ness Rob W. , Johnson Marc T. J.
Published: March 2020

Cities are emerging as models for addressing the fundamental question of whether populations evolve in parallel to similar environments. Here, we examine the environmental factors that drive the evolution of parallel urban-rural clines in a Mendelian trait—the cyanogenic antiherbivore defense of white clover (Trifolium repens). Previous work suggested urban-rural gradients in frost and snow depth could drive the evolution of reduced hydrogen cyanide (HCN) frequencies in urban populations. Here, we sampled over 700 urban and rural clover populations across 16 cities along a latitudinal transect in eastern North America. In each population, we quantified changes in the frequency of genotypes that produce HCN, and in a subset of the cities we estimated the frequency of the alleles at the two genes (CYP79D15 and Li) that epistatically interact to produce HCN. We then tested the hypothesis that cold climatic conditions are necessary for the evolution of cyanogenesis clines by comparing the strength of clines among cities located along a latitudinal gradient of winter temperature and frost exposure. Overall, half of the cities exhibited urban-rural clines in the frequency of HCN, whereby urban populations evolved lower HCN frequencies. Clines did not evolve in cities with the lowest temperatures and greatest snowfall, supporting the hypothesis that snow buffers plants against winter frost and constrains the formation of clines. By contrast, the strongest clines occurred in the warmest cities where snow and frost are rare, suggesting that alternative selective agents are maintaining clines in warmer cities. Some clines were driven by evolution at only CYP79D15, consistent with stronger and more consistent selection on this locus than on Li. Together, our results demonstrate that urban environments often select for similar phenotypes, but different selective agents and targets underlie the evolutionary response in different cities.
Predictive models for influence of primary delays using high‐speed train operation records
Authors: Li Zhongcan , Huang Ping , Wen Chao , Tang Yixiong , Jiang Xi
Published: March 2020

Primary delays are the driving force behind delay propagation, and predicting the number of affected trains (NAT) and the total time of affected trains (TTAT) due to primary delay (PD) can provide reliable decision support for real‐time train dispatching. In this paper, based on real operation data from 2015 to 2016 at several stations along the Wuhan–Guangzhou high‐speed railway, NAT and TTAT influencing factors were determined after analyzing the PD propagation mechanism. The eXtreme Gradient BOOSTing (XGBOOST) algorithm was used to establish a NAT predictive model, and several machine learning methods were compared. The importance of different delayinfluencing factors was investigated. Then, the TTAT predictive model (using support vector regression (SVR) algorithms) was established based on the NAT predictive model. Results indicated that the XGBOOST algorithm performed well with the NAT predictive model, and SVR was the optimal model for TTAT prediction under the verification index (i.e., the ratio of the difference between the actual and predicted value was less than 1/2/3/4/5 min). Real operational data in 2018 were used to test the applicability of the NAT and TTAT models over time, and findings suggest that these models exhibit sound applicability over time based on XGBOOST and SVR, respectively.
Is implied volatility more informative for forecasting realized volatility: An international perspective
Authors: Liang Chao , Wei Yu , Zhang Yaojie
Published: March 2020

Inspired by the commonly held view that international stock market volatility is equivalent to cross‐market information flow, we propose various ways of constructing two types of information flow, based on realized volatility (RV) and implied volatility (IV), in multiple international markets. We focus on the RVs derived from the intraday prices of eight international stock markets and use a heterogeneous autoregressive framework to forecast the future volatility of each market for 1 day to 22 days ahead. Our Diebold‐Mariano tests provide strong evidence that information flow with IV enhances the accuracy of forecasting international RVs over all of the prediction horizons. The results of a model confidence set test show that a market's own IV and the first principal component of the international IVs exhibit the strongest predictive ability. In addition, the use of information flows with IV can further increase economic returns. Our results are supported by the findings of a wide range of robustness checks.
Neoadjuvant chemotherapy followed by surgery for HPV‐associated locoregionally advanced oropharynx cancer
Authors: Sadeghi Nader , Mascarella Marco A. , Khalife Sarah , Ramanakumar Agnihotram V. , Richardson Keith , Joshi Arjun S. , Taheri Reza , Fuson Andrew , Bouganim Nathaniel , Siegel Robert
Published: March 2020

Background

Neoadjuvant chemotherapy followed by surgery (NAC + S), a paradigm based on systemic escalation coupled with surgery‐based de‐escalation, is under investigation for treatment of HPV‐associated oropharynx cancer (OPC).

Methods

Prospective cohort of patients with non‐metastatic, p16 positive OPC enrolled in a clinical trial of NAC + S was compared to a historic cohort of patients undergoing concurrent chemoradiation (CCRT) to compare disease‐free survival (DFS).

Results

Fifty‐five patients were treated with NAC + S and 142 with CCRT. Stage‐matched patients undergoing CCRT had higher frequency of smoking and alcohol consumption. 5‐year DFS in the NAC + S group was 96.1% (95% CI 90.8‐100) compared to 67.6% (95% CI 50.7‐84.5) for CCRT (P = .01). At 12 months from treatment, 24.5% of patients undergoing CCRT and none of the patients in the NAC + S were feeding tube dependent (P < .0001).

Conclusion

NAC + S may be a novel approach for HPV‐associated OPC as it provides lower feeding tube dependence and improved survival compared to stage‐matched patients undergoing CCRT.
Institutional experience of 200 consecutive papillary thyroid carcinoma patients in transoral robotic thyroidectomy surgeries
Authors: Park Dawon , Kim Hoon Yub , Kim Hong Kyu , You Ji‐Young , Dionigi Gianlorenzo , Russell Jonathon O. , Tufano Ralph P.
Published: March 2020

Background

We evaluated the outcomes of patients with papillary thyroid carcinoma (PTC) who underwent transoral robotic thyroidectomy (TORT).

Methods

We retrospectively analyzed the perioperative outcomes of 200 patients (170 women and 30 men) with PTC who underwent TORT at a single center between March 2016 and February 2018.

Results

There were 182 and 13 cases of lobectomy and total thyroidectomy, respectively, with corresponding mean operative times of 200.6 ± 31.2 and 265.7 ± 63.0 minutes. On average, 5.6 ± 3.45 lymph nodes were retrieved per patient. There were 12 cases of perioperative morbidity. No conversion to endoscopic or conventional open surgery was noted. In a subgroup analysis for predictors of difficult TORT, patient sex was the only factor showing a significant operative time difference between a difficult and a nondifficult thyroidectomy.

Conclusion

TORT can be performed safely in patients with PTC without serious complications.
Clinical management of emerging sinonasal malignancies
Authors: Contrera Kevin J. , Woody Neil M. , Rahman Mobeen , Sindwani Raj , Burkey Brian B.
Published: March 2020

Several emerging sinonasal malignancies have recently been described in the pathology literature. Although not all distinctly classified by the World Health Organization, these rare tumors present a management challenge to surgeons and oncologists. While prior studies have summarized histologic details, a clinically focused review is currently lacking in the literature. This review describes the presentation, histopathology, imaging, treatment, and prognosis of newly described or recently evolving sinonasal malignancies while highlighting the distinguishing features of these entities. It includes teratocarcinosarcoma, human papillomavirus‐related multiphenotypic carcinoma, biphenotypic sinonasal sarcoma, sinonasal renal cell‐like adenocarcinoma, NUT‐midline carcinoma, squamous cell carcinoma associated with inverted papilloma, sinonasal undifferentiated carcinoma, and INI‐1‐deficient sinonasal carcinoma. By describing the diagnosis, treatment, and prognosis of these recently defined entities, this clinical review aims to help guide oncologists in the clinical management of these patients.
Neurologic sequelae following radiation with and without chemotherapy for oropharyngeal cancer: Patient reported outcomes study
Authors: Garden Adam S. , Kamal Mona , Mohamed Abdallah S. R. , Frank Steven J. , Lewin Jan S. , Lai Stephen Y. , Morrison William H. , Phan Jack , Ferrarotto Renata , Rosenthal David I. , Hutcheson Katherine A. , Fuller Clifton D. , Gunn Gary B.
Published: March 2020

Background

There is little data describing neurocognitive late sequelae in patients treated for oropharyngeal cancer.

Methods

Using PROs, scores for “numbness/tingling” and “difficulty remembering” were assessed. Wilcoxon testing was utilized to compare mean assessment scores (1‐10) between treatment subgroups.

Results

Four‐hundred ninety‐seven patients were evaluated and 267 (54%) received chemotherapy. The mean score for numbness/tingling for patients receiving radiation alone was 0.99 and for each chemotherapy subgroup were: Induction chemotherapy (IC), 1.35 (n = 99); concurrent chemotherapy (CCRT), 1.04 (n = 111) and IC + CCRT, 2.48 (n = 57); 30% of patients who received IC + CCRT had scores ≥5. The mean scores for difficulty remembering were XRT: 1.44, chemotherapy: 1.45, and IC + CCRT subgroup: 2.42.

Conclusions

The symptom burden related to peripheral neuropathy and cognitive complaints was minimal. A minority of patients reported high burdens. Particularly, 30% of patients receiving IC + CCRT described moderate to severe numbness/tingling.
Bi‐institutional experience of transoral endoscopic thyroidectomy: Challenges and outcomes
Authors: Hong Yong Tae , Ahn Jong‐hyuk , Kim Jae Hwan , Yi Jin Wook , Hong Ki Hwan
Published: March 2020

Background

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a novel remote‐access endoscopic approach. In this study, we compared the surgical outcomes of TOETVA with those of conventional transcervical approach (TCA) in two tertiary hospitals.

Methods

A total of 82 patients were done by TOETVA and 233 patients received TCA between January 2018 and April 2019. Propensity score matching was used to reduce selection bias.

Results

Operation time of the TOETVA group was longer than that of the TCA group. The mean number or retrieved lymph nodes were significantly higher in the TOETVA group. No significant difference was observed in the overall perioperative complications.

Conclusion

TOETVA is technically acceptable when compared to TCA in terms of equal baseline characteristics of patients. Although future large‐scale multicenter studies with longer follow‐up periods are needed, we expect this novel technique can be performed not only for cosmetic purposes but also for patients with papillary thyroid carcinoma.
PTPN11 mutations in canine and human disseminated histiocytic sarcoma
Authors: Hédan Benoit , Rault Mélanie , Abadie Jérôme , Ulvé Ronan , Botherel Nadine , Devauchelle Patrick , Copie‐Bergman Christiane , Cadieu Edouard , Parrens Marie , Alten Julia , Zalcman Emmanuelle L. , Cario Gunnar , Damaj Gandhi , Mokhtari Karima , Le Loarer Francois , Coulomb‐Lhermine Aurore , Derrien Thomas , Hitte Christophe , Bachelot Laura , Breen Matthew , Gilot David , Blay Jean Y. , Donadieu Jean , André Catherine
Published: March 2020

In humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes. Its rarity and heterogeneity explain that treatment remains a challenge. Sharing high clinical and histopathological similarities with human HS, the canine HS is conversely frequent in specific breeds and thus constitutes a unique spontaneous model for human HS to decipher the genetic bases and to explore therapeutic options. We identified sequence alterations in the MAPK pathway in at least 63.9% (71/111) of HS cases with mutually exclusive BRAF (0.9%; 1/111), KRAS (7.2%; 8/111) and PTPN11 (56.75%; 63/111) mutations concentrated at hotspots common to human cancers. Recurrent PTPN11 mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified PTPN11 mutations in 3/19 (15.7%) human HS patients. Thus, we propose PTPN11 mutations as key events for a specific subset of human and canine HS: the visceral disseminated form. Finally, by testing drugs targeting the MAPK pathway in eight canine HS cell lines, we identified a better anti‐proliferation activity of MEK inhibitors than PTPN11 inhibitors in canine HS neoplastic cells. In combination, these results illustrate the relevance of naturally affected dogs in deciphering genetic mechanisms and selecting efficient targeted therapies for such rare and aggressive cancers in humans.
Multiple low‐frequency and rare HLA‐B allelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province, southern China
Authors: Tian Wei , Zhu FaMing , Cai JinHong , Li LiXin , Jin HeKun , Wang WenYi
Published: March 2020

In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)‐B locus by Sanger sequencing exons 2–4. Besides confirming the NPC association with HLA‐B*46:01 allele, HLA‐A*02:07‐B*46:01 and HLA‐A*33:03‐B*58:01 haplotypes (all positive), and HLA‐B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low‐frequency and rare alleles or lineages, including HLA‐B*07, ‐B*27:04, ‐B*39, ‐B*51:02 and ‐B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all pcorrected < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA‐A and HLA‐B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA‐B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti‐VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55–48.81), p < 0.0001]. HLA‐B allelic variation did not associate with seropositivity for anti‐VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low‐frequency and rare HLA‐B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.
Interleukins 6/8 and cyclooxygenase‐2 release and expressions are regulated by oxidative stress‐JAK2/STAT3 signaling pathway in human bronchial epithelial cells exposed to particulate matter ≤2.5 μm
Authors: Xu Zhenzhen , Wu Hongyan , Zhang Hongmei , Bai Jianying , Zhang Zhihong
Published: March 2020

Atmospheric particulate matter with a diameter ≤2.5 μm (PM2.5) can induce inflammation of the respiratory system, which is the pathological basis of asthma or other respiratory diseases; however, the underlying regulation mechanism has not been clearly addressed. The aim of this study was to explore the potential role of the oxidative stress‐JAK/STAT signaling pathway in the inflammation of human bronchial epithelial cells induced by PM2.5. The human bronchial epithelial cell line 16HBE cells were stimulated with PM2.5 at 50 and 100 μg/mL doses for 12 or 24 hours. Intracellular reactive oxygen species (ROS) was detected using flow cytometry. Gene and protein expressions of JAK2, STAT3 and cyclooxygenase 2 (COX‐2) were determined using reverse transcription‐polymerase chain reaction and western blotting, respectively. The ratio of intracellular glutathione/glutathione disulfide (GSH/GSSG) and the levels of interleukin (IL)‐6 and IL‐8 in cellular supernatant were analyzed using enzyme‐linked immunosorbent assay. The results indicated that PM2.5 treatment significantly increased gene expressions of JAK2/STAT3 and protein levels of p‐JAK2/p‐STAT3, accompanied by increased intracellular ROS levels, decreased GSH/GSSG ratio at 50 and 100 μg/mL of PM2.5, and significantly enhanced levels of IL‐6, IL‐8 and COX‐2 at a dose of 100 μg/mL. Pretreatment with N‐acetyl‐l‐cysteine (NAC) attenuated the oxidative stress induced by PM2.5; similarly, pretreatment with AG490 (an inhibitor of JAK) decreased the cytokine levels stimulated by PM2.5. Therefore, we concluded that PM2.5 exposure could activate oxidative stress‐JAK2/STAT3 signaling pathway, elevate the levels of IL‐6, IL‐8 and COX‐2 in 16HBE cells, which can be inhibited by the NAC or AG490.
Ubiquitin-Specific Protease 34 Inhibits Osteoclast Differentiation by Regulating NF-κB Signaling
Authors: Li Qiwen , Wang Mengyuan , Xue Hanxiao , Liu Weiqing , Guo Yuchen , Xu Ruoshi , Shao Bin , Yuan Quan
Published: March 2020

The ubiquitination and deubiquitination enzymes ensure the stability and proper function of most cellular proteins. Disturbance of either enzyme compromises tissue homeostasis. We recently have identified that the ubiquitin-specific protease 34 (USP34) contributes to bone formation by promoting osteogenic differentiation of mesenchymal stem cells. However, its role in bone resorption, which couples bone formation, remains unknown. Here we show that knockdown of Usp34 promotes osteoclast differentiation of RAW264.7 cells. Conditional knockout of Usp34 in bone marrow–derived macrophages (BMMs) or in osteoclasts leads to elevated osteoclast function and low bone mass. Mechanically, we identify that USP34 restrains NF-κB signaling by deubiquitinating and stabilizing the NF-κB inhibitor alpha (IκBα). Overexpression of IκBα represses osteoclastic hyperfunction of Usp34-deficient RAW264.7 cells. Collectively, our results show that USP34 inhibits osteoclastogenesis by regulating NF-κB signaling. © 2020 American Society for Bone and Mineral Research.
Postnatal Conditional Deletion of Bmal1 in Osteoblasts Enhances Trabecular Bone Formation Via Increased BMP2 Signals
Authors: Qian Zhuang , Zhang Ying , Kang Xiaomin , Li Huixia , Zhang Yan , Jin Xinxin , Gao Xin , Xu Mao , Ma Zhengmin , Zhao Liting , Zhang Zhuanmin , Sun Hongzhi , Wu Shufang
Published: March 2020

A large number of studies in recent years indicated the involvement of peripheral circadian clock in varied pathologies. However, evidence regarding how peripheral clocks regulate bone metabolism is still very limited. The present study aimed to investigate the direct role of Bmal1 (the key activator of peripheral circadian clock system) in vivo during bone developmental and remodeling stages using inducible osteoblast-specific Bmal1 knockout mice. Unexpectedly, the removal of Bmal1 in osteoblasts caused multiple abnormalities of bone metabolism, including a progressive increase in trabecular bone mass in as early as 8 weeks, manifested by an 82.3% increase in bone mineral density and 2.8-fold increase in bone volume per tissue volume. As mice age, an increase in trabecular bone mass persists while cortical bone mass decreases by about 33.7%, concomitant with kyphoscoliosis and malformed intervertebral disk. The increased trabecular bone mass is attributed to increased osteoblast number and osteoblast activity coupled with decreased osteoclastogenesis. Remarkably, the ablation of Bmal1 in osteoblasts promoted the expression level of Bmp2 and phosphorylation of SMAD1, whereas the attenuation of BMP2/SMAD1 signaling partially alleviated the effects of Bmal1 deficiency on osteoblast differentiation and activity. The results revealed that Bmal1 was a transcriptional silencer of Bmp2 by targeting the Bmp2 promoter. The peripheral clock gene Bmal1 in osteoblasts was crucial to coordinate differential effects on trabecular and cortical bones through regulating BMP2/SMAD1 during bone development, thus providing novel insights into a key role of osteoblast Bmal1 in homeostasis and integrity of adult bones. © 2020 American Society for Bone and Mineral Research.