bluuebunny/crossref_metadata_2025 huggingface dataset:
Cocrystals “Divorce and Marriage”: When a Binary System Meets an Active Multifunctional Synthon in a Ball Mill
Authors: Dudek Marta K. , Śniechowska Justyna , Wróblewska Aneta , Kaźmierski Sławomir , Potrzebowski Marek J.
Published: June 2020

A well‐defined and stable “AB” binary system in the presence of “C” a crystalline synthon ground in a ball mill undergoes selective transformation in the solid state according to the equation AB+C→AC+B. When the amount of C is increased two times then the equation AB+2C→AC+BC is valid. The other variants are more complex. The pathway BC+A is allowed and leads to the AC and B products. The pathway AC+B is not preferred, and no transformation is observed. These non‐obvious correlations were observed for cocrystal of barbituric acid (BA):thiobarbituric acid (TBA) recently reported by Shemchuk et al. (Chem. Commun. 2016, 52, 11815–11818) in the presence of 1‐hydroxy‐4,5‐dimethyl‐imidazole 3‐oxide (HIMO). This synthon shows high affinity for the BA0.5TBA0.5 cocrystal as well for its individual components, BA and TBA. Single‐quantum, double‐quantum (SQ‐DQ) 2D 1H very fast MAS NMR with a spinning rate of 60 kHz was employed as a basic and most diagnostic tool for the study of cocrystals transformations. Analysis of the experimental data was supported by theoretical calculations, including computation of the stabilization energy, Estab, defined as the energy difference between the energy of a co‐crystal and the sum of the energies of particular components in the respective stoichiometric ratios. Two mechanisms of synthon replacement have been proposed. Pathway 1 assumes a concerted mechanism of substitution. In this approach, synthon attack is synchronized in time with the departure of one of the components of the binary system. Pathway 2 implies a non‐concerted process, with an intermediate stage in which three separate components are present. Evidence suggesting a preference for Pathway 2 is shown.
Resonance Assisted Chalcogen Bonding as a New Synthon in the Design of Dyes
Authors: Gurbanov Atash V. , Kuznetsov Maxim L. , Mahmudov Kamran T. , Pombeiro Armando J. L. , Resnati Giuseppe
Published: June 2020

Intramolecular chalcogen bonding in arylhydrazones of sulfamethizole is strengthened by conjugation in the π‐system of a noncovalent five‐membered ring. The S⋅⋅⋅O distance in the sulfamethizole moiety of these compounds ranges from 2.698(3) to 2.806(15) Å, which indicates its strong dependence on the attached arylhydrazone fragments. Information on the nature of the intramolecular chalcogen bond was afforded by DFT calculations.
Tetrazole Azasydnone (C2N7O2H) And Its Salts: High‐Performing Zwitterionic Energetic Materials Containing A Unique Explosophore
Authors: Gettings Matthew L. , Thoenen Michael T. , Byrd Edward F. C. , Sabatini Jesse J. , Zeller Matthias , Piercey Davin G.
Published: June 2020

This work reports the first compound containing both a tetrazole and an azasydnone ring, a unique energetic material. Several energetic salts of the tetrazole azasydnone were synthesized and characterized, leading to the creation of new secondary and primary explosives. Molecular structures are confirmed by 1H and 13C NMR, IR spectroscopy, and X‐ray crystallographic analysis. The high heats of formation, fast detonation velocities, and straight‐forward synthesis of energetic azasydnones should capture the attention of future energetics research.
Nonclassical Recrystallization
Authors: Brunner Julian , Maier Britta , Rosenberg Rose , Sturm Sebastian , Cölfen Helmut , Sturm Elena V.
Published: June 2020

Applications in the fields of materials science and nanotechnology increasingly demand monodisperse nanoparticles in size and shape. Up to now, no general purification procedure exists to thoroughly narrow the size and shape distributions of nanoparticles. Here, we show by analytical ultracentrifugation (AUC) as an absolute and quantitative high‐resolution method that multiple recrystallizations of nanocrystals to mesocrystals is a very efficient tool to generate nanocrystals with an excellent and so‐far unsurpassed size‐distribution (PDIc=1.0001) and shape. Similar to the crystallization of molecular building blocks, nonclassical recrystallization removes “colloidal” impurities (i.e., nanoparticles, which are different in shape and size from the majority) by assembling them into a mesocrystal. In the case of nanocrystals, this assembly can be size‐ and shape‐selective, since mesocrystals show both long‐range packing ordering and preferable crystallographic orientation of nanocrystals. Besides the generation of highly monodisperse nanoparticles, these findings provide highly relevant insights into the crystallization of mesocrystals.
Total Synthesis of Terpioside B
Authors: Inaba Kazuki , Endo Masato , Iibuchi Naoto , Takahashi Daisuke , Toshima Kazunobu
Published: June 2020

The first total synthesis of terpioside B (1) has been accomplished. Key steps include the stereoselective installments of a set of challenging 1,2‐cis‐glycosidic linkages. Thus, α(1,4)‐linked d‐galactoside was effectively constructed from a 1,2‐anhydrogalactose donor and an unprotected 1,6‐anhydrogalactose acceptor by using a boron‐mediated aglycon delivery (BMAD) method. In addition, α‐l‐fucofuranosides were stereoselectively and simultaneously constructed by remote group‐assisted 1,2‐cis‐α‐stereoselective glycosylations.
Enantiopure ethyl 2,3‐dibromopropionate: Enantioselective synthesis vs preparative HPLC enantioseparation of racemate on multigram scale
Authors: Pham Hong‐Ngoc , Arrault Axelle , Vanthuyne Nicolas , Acherar Samir
Published: June 2020

Racemic ethyl 2,3‐dibromopropionate, commercially available at low price, is a key intermediate used in the synthesis of several heterocycle fragments, which are present in many biologically active compounds. Surprisingly, the enantiomers are not commercially available and have never been described in the literature. In this work, we undertook two different strategies to obtain these enantiomers, which are enantioselective synthesis and preparative HPLC enantioseparation of commercially available racemate on multigram scale. The first strategy has proved inadequate because racemization occurred during the synthesis (ee ≈ 9‐50%). Conversely, the second strategy produced a very good enantioseparation of commercially available racemate (ee > 99.5% for both enantiomers) on multigram scale.
Kostenkalkulation im Anlagenbau: Modell zur Bewertung der Konkurrenzfähigkeit im Entwicklungsstadium
Authors: Horst Stephan , Höfer Jannik , Kleine‐Möllhoff Peter , Wennagel Fabienne , Wiech Nils , Pfost Michael , Atmaca Bercan , Gries Julia , Epple Rolf
Published: June 2020

Während Grundchemikalien größtenteils im industriellen Maßstab mittels verfahrenstechnisch optimierter Großanlagen hergestellt werden, entwickeln Forschungsinstitute biobasierte Prozesse zur Herstellung von Plattformchemikalien im Labor‐ und Pilotmaßstab. Im Rahmen dieser Arbeit wird ein Kostenkalkulationsmodell zur Abschätzung der Investitions‐ und Betriebskosten verfahrenstechnischer Anlagen vorgestellt, auf dessen Basis die ökonomische Konkurrenzfähigkeit in der Entwicklung befindlicher Verfahren ermittelt werden kann. Das Modell ist für Anwendungen im industriellen Maßstab geeignet.
Managementsysteme helfen – gerade in Krisenzeiten
Authors: Reusche Uwe
Published: June 2020

Managementsysteme wie das „Objectives and Key Results“ (OKR) und das „Management by Objectives“ (MbO) sind nur Hilfsmittel. Entscheidend ist, wie sie genutzt werden. Das gilt insbesondere im Vertrieb, der gerade in Krisenzeiten oft rasch auf veränderte Ra
Report: Alle sollen an Bord bleiben
Authors: Sieß Wolfgang
Published: June 2020

Das gute Abschneiden von Endress+Hauser im Geschäftsjahr 2019 über alle Arbeitsgebiete, Branchen und Regionen hinweg war zwar Inhalt der Bilanz‐Pressekonferenz des Schweizer Messtechnik‐ und Automatisierungsspezialisten. Aber es war in Zeiten der Pandemie natürlich nicht die Hauptsache der erstmals ausschließlich online abgehaltenen Veranstaltung.
Mit dem Ohr an der Anlage
Authors: Michael Fischer Klaus , Sahin Levent
Published: June 2020

Korrosionsangriffe und Fehlstellen können fortschreitende Schäden an Druckgeräten hervorrufen. Deshalb sind Druckbehälter, Rohrleitungen und andere drucktragende Bauteile nach Betriebssicherheitsverordnung (BetrSichV) wiederkehrend zu prüfen. Während bei
Kleinste Tropfen im Visier
Authors: Hecker Meiko
Published: June 2020

Die Bergstraße ist berühmt für gute Tropfen. Aber nicht nur jeder Tropfen Wein wird hier gehegt und gepflegt. Der Messtechnikspezialist AOM‐Systems aus Heppenheim behält mit Hightech‐Lösungen auch kleinste Tropfen stets im Auge. Mit großer Geschwindigkeit und Präzision überwachen seine Geräte in Echtzeit die Sprayqualität von Zerstäubungsprozessen in der Verfahrenstechnik. Das Messsystem wird unter anspruchsvollsten Produktionsbedingungen eingesetzt.
Experimental study and reproduction of a color‐changing bath ball using a smartphone as a photometer
Authors: Rautenstrauch Hanne
Published: June 2020

Gemäß den Bildungsstandards für den mittleren Schulabschluss und den einheitlichen Prüfungsanforderungen für das Abitur ist es im Bereich der Erkenntnisgewinnung ein wesentliches Ziel des Chemieunterrichts, Schülerinnen und Schüler zum Planen von Experimenten, zum Entwickeln von Hypothesen und zum Durchführen und Bewerten der Experimente hinsichtlich einer eingangs gestellten Problemstellung zu befähigen. Um diese Kompetenzen anzubahnen, können offene Experimentalaufgaben, die ein forschendes Lernen ermöglichen und fordern, im Unterricht eingesetzt werden. Eine Möglichkeit für eine alltagsgegenstandsbezogene Problemstellung bietet die Farbwechselbadekugel, welche mit Hilfe nasschemischer Analyseverfahren, einem Smartphone‐Photometer und mit Papierchromatographie von Schülerinnen und Schülern auf ihre Bestandteile hin untersucht und anschließend nachgebaut werden kann.
Pharmacokinetics of Single and Multiple Doses of Omega‐3 Carboxylic Acids in Healthy Chinese Subjects: A Phase I, Open‐Label Study
Authors: Jing Shan , Zhang Zhenxian , Chen Xiaowen , Miao Rui , Nilsson Catarina , Lin Yang
Published: June 2020

In patients with coronary heart disease undergoing primary prevention, hypertriglyceridemia is a residual risk for cardiovascular events. Omega‐3 carboxylic acid (OM3‐CA), a mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be beneficial in reducing triglyceride levels. As part of the clinical development program of OM3‐CA in China, this phase I study evaluated the pharmacokinetics, safety, and tolerability profile of OM3‐CA in healthy subjects. The pharmacokinetic results of this study were also compared with those of available data for Western populations. Fourteen healthy Chinese subjects (aged 18‐45 years) received once‐daily oral OM3‐CA 4 g for 14 consecutive days. Pharmacokinetic parameters were assessed from both baseline‐uncorrected and baseline‐corrected plasma concentrations vs time profile of EPA, DHA, and EPA plus DHA. Following single and multiple oral doses of OM3‐CA, the absorption of EPA, DHA, and EPA plus DHA was steady with median tmax occurring at 5.5–6 hours after both single and multiple dosing. Close to steady‐state concentrations in plasma were reached after 14 days of continuous once‐daily dosing, and accumulation was confirmed for EPA, DHA, and EPA plus DHA. Of the 14 subjects treated with OM3‐CA, 6 (42.9%) reported at least 1 adverse event (diarrhea) during the study, which was determined as mild and treatment emergent. No serious adverse events were reported. In summary, the pharmacokinetic profile of oral OM3‐CA 4 g after single and multiple dosing in healthy Chinese subjects is consistent with that observed in other ethnic populations.
BODIPY on Board of Sugars: A Short Enlightened Journey up to the Cells
Authors: Barattucci Anna , Campagna Sebastiano , Papalia Teresa , Galletta Maurilio , Santoro Antonio , Puntoriero Fausto , Bonaccorsi Paola
Published: June 2020

BODIPY dyes have unique properties including: good stability in many solvents, high extinction coefficients, stability to light, sharp fluorescence emissions in the visible region with high fluorescence quantum yields. Moreover, through small chemical modifications of the skeleton, their luminescence properties can be finely tuned. As a consequence, during the last decades, this family of chromophores found extensive application in a wide range of fields. Carbohydrates play a relevant role in living organisms: their tasks range from energy storage to structural constituents of cells and tissues, they are involved in a variety of molecular recognition phenomena of physiological and biological relevance. The cyclic structure of natural D‐monosaccharides, also offers the conditions to use carbohydrates as building‐blocks in the construction of more complex, supramolecular structures. With these assumptions, in the last years our research in this field has focused on the study of synthesis, the photophysical features, and the application in the biomedical field of molecules that bear the synergic presence of these two tools. Pointing on the rationalization of this research, this article will provide a synthetic review of our last‐year's results in the field of BODIPY/glycosyl species, that can be classified in two principal sections: a) the rational synthesis and the photophysical studies of BODIPY dyads and antennas containing different kind of sugar units as scaffolds, ranging from mono‐ to disaccharide patterns, and b) the synthetic functionalization and modification of suitable BODIPY structures, for their punctual application in the field of bio‐imaging.
A parameter estimation method for time‐frequency‐overlapped frequency hopping signals based on sparse linear regression and quadratic envelope optimization
Authors: Wang Liandong , Liu Zhipeng , Feng Yuntian , Liu Xiaoguang , Xu Xiong , Chen Xiang
Published: June 2020

The frequency hopping (FH) signals have well‐documented merits for commercial and military fields due to near‐far resistance and robustness to jamming. Therefore, the parameter estimation of FH signals is an important task for subsequent information acquisition and autonomous electronic countermeasure or attack. However, under the complex electromagnetic environment, there always exist overlaps in the time‐frequency domain among multiple signals, which bring poor signal sparsity and make the estimation more challenging. In this paper, a novel parameter estimation approach is developed for the time‐frequency‐overlapped FH signals under single‐channel reception. The exact solution is mainly composed of the sparse linear regression‐based matrix optimization (SLR‐MO) and quadratic envelope optimization (QEO). SLR‐MO highlights the removal of noise and distortion features for improving the overall sparsity and time‐frequency resolution. QEO further eliminates parts of the interfering signal features and outliers and then extracts and optimizes the average time‐frequency ridge to complete the parameter estimation (hopping instants, period, and carriers). Simulation results demonstrate that the developed estimator outperforms the traditional methods in the scope of application, estimation accuracy, and the robustness under low signal‐to‐noise ratio (SNR).
Advances in N‐Heterocyclic Carbene Catalysis for Natural Product Synthesis
Authors: Que Yonglei , He Haibing
Published: June 2020

N‐heterocyclic carbenes (NHCs) efficiently catalyze new bond formations with high regio‐ and stereoselectivity through umpolung and non‐umpolung processes. These processes typically involve four species: Breslow intermediates, homoenolates, enolates, and α,β‐unsaturated acyl azoliums. Organic syntheses are increasingly relying on NHC catalysis, and this minireview highlights developments in NHC‐catalyzed reactions that, over the past two decades, have been used as key steps in the total syntheses of natural products. Crucial intermediates and reaction mechanisms are presented in detail.
Determination of the Absolute Configurations of Chiral Alkanes – An Analysis of the Available Tools
Authors: Saito Fumito , Schreiner Peter R.
Published: June 2020

Knowledge of absolute configurations (ACs) is crucial to understand the properties and functions of chiral molecules. Although the development of asymmetric reactions has enabled access to a large variety of enantioenriched compounds, stereochemical assignments of chiral molecules, especially chiral alkanes, remain challenging. In this Minireview, we first summarize common analytical techniques for AC determination with a focus on chiral alkanes as analytical targets. Next, we describe some of our efforts over the last 20 years on syntheses and AC determination of chiral alkanes including [123]tetramantane, hexadeuterated neopentane, and trans‐perhydroazulene. Lastly, microscopic techniques and the crystalline sponge method are discussed as particularly promising approaches to revolutionize the field of stereochemical analysis.
In vivo kinetics of the genotoxic and cytotoxic activities of cladribine and clofarabine
Authors: Quezada‐Vidal Jesús , Ortíz‐Muñiz Rocío , Cervantes‐Ríos Elsa , Cruz‐Vallejo Virginia , Morales‐Ramírez Pedro
Published: June 2020

The aim of the present in vivo study was to determine the kinetics of the genotoxic and cytotoxic activities of cladribine and clofarabine in mouse normoblasts using flow cytometry. Mice in groups of five were treated with cladribine or clofarabine. Blood samples were obtained from the mouse tails before treatment and every 8 hr posttreatment for 72 hr. These samples were cytometrically scored for micronucleated reticulocytes (RETs), and the percentage of RETs was determined. The results showed that clofarabine and cladribine have early cytotoxic effects that are related to the genotoxic effects reported in previous studies; the drugs have both complex long‐lasting genotoxic and cytotoxic kinetic activity, with similar profiles that suggest a relationship between the genotoxic and cytotoxic parameters. The initial genotoxkinetics timing of clofarabine is equivalent to those of difluorodeoxycytidine, likely because both agents inhibit DNA polymerase. Clofarabine shows a higher genotoxic and cytotoxic efficiency than cladribine, in agreement with previous results.
Design of a novel hybrid control strategy for multi‐inverter parallel system for resonance suppression
Authors: Zheng Feng , Lin Xiangqun , Zhang Yachao , Deng Changhong
Published: June 2020

Comparing with the LCL‐type single‐inverter parallel system, the multi‐inverter parallel system has more complex resonance characteristics which are generated by three type resonance sources (reference current changing in the inverter control system, reciprocal effect among multi‐inverters and grid background harmonic) and cause great negative effects on power system. In order to suppress the resonance problem of LCL‐type multi‐inverters parallel system, a novel control strategy is proposed in this paper based on model current predictive control (MCPC) and two‐degree‐of‐freedom control. Through MCPC, this strategy can reduce the number of current inner‐loop PI of control layer and remove PWM module. Then, a potential robustness can be obtained. From the outer loop of control layer perspective, because MCPC's value function consists of inverter's output current and reference current of control layer inner loop, they can be approximately regarded as equal. And then through constructing the inverse model of control object, the two‐degree‐of‐freedom control can be introduced to realized transfer function unitarization of control layer's outer loop, so that the order difference between numerator's highest order term and denominator's highest order term of inverter resonance transfer function can be reduced. Accordingly, it can be found that with the three type resonance sources, there is no peak value in their resonance transfer functions and their gains all present attenuation effects. Therefore, the resonance problems of multi‐inverter parallel system can be eliminated. Through the theoretical derivation and simulation results, it can be proved that the proposed method can not only enhance the transient performance of multi‐inverter parallel system, but also its resonance problems.
Machine‐learning‐based surface tension model for multiphase flow simulation using particle method
Authors: Liu Xiaoxing , Morita Koji , Zhang Shuai
Published: June 2020

Particle methods have shown their potential for simulating multiphase flows due to the convenience in capturing interfaces. However, when it comes to estimate the surface tension, calculation of the curvature of the interface remains challenging. Traditional methods are based on derivative models to estimate the curvature analytically from the particle number density or color function that marks different phases. It is difficult to estimate the curvature accurately in traditional derivative models. In this study, background cells are built up and are used to predict the curvature through machine learning. By training on a data set generated using circles of varying sizes, a relation function is found to predict the curvature from the particle distribution near the interface. Together with the enhanced schemes developed in our previous study, multiphase flows with surface tension are studied within the framework of the moving particle semi‐implicit method.
Group analysis of distance matrices
Authors: Wang Jinjuan , Li Jialu , Xiong Wenjun , Li Qizhai
Published: June 2020

Distance‐based regression model has become a powerful approach to identifying phenotypic associations in many fields. It is found to be particularly useful for high‐dimensional biological and genetic data with proper distance or similarity measures being available. The pseudo F statistic used in this model accumulates information and is effective when the signals, that is the variations represented by the eigenvalues of the similarity matrix, scatter evenly along the eigenvectors of the similarity matrix. However, it might lose power for the uneven signals. To deal with this issue, we propose a group analysis on the variations of signals along the eigenvalues of the similarity matrix and take the maximum among them. The new procedure can automatically choose an optimal grouping point on some given thresholds and thus can improve the power evidence. Extensive computer simulations and applications to a prostate cancer data and an aging human brain data illustrate the effectiveness of the proposed method.
Cenozoic tectonic evolution of South China: A brief review, and new insights from the Huangshadong‐Shiba area, south‐east China
Authors: Kuang Jian , Wang Shuai , Qi Shihua , Xiao Zhicai , Zhang Min , Wang Yousheng
Published: June 2020

The Cenozoic tectonic dynamic process controlled by the Pacific subduction and Tethyan subduction/collision in South China are still controversial and lacks geological evidence of intracontinental deformation to define. Here, we focused on the Huangshadong‐Shiba area (HSA) in the south‐eastern coastal area of China. This study aims to obtain multi‐stage geological events by an integrated multidisciplinary investigation to decipher the multiple tectonic deformation in Cenozoic South China. We found that the Jurassic and Cretaceous granite not only dominates in surface magmatic rocks but also integrates into a whole with buried depth more than 2 km. This plate‐like granite (it means the occurrence of granite is like a tremendous plate) with thickness more than 3 km is sliced by Heyuan Fault, Renzishi Fault, and Zijin‐Boluo Fault. The basalts in the Shiba Basin have an Ocean Island Basalt‐like property, and the Heyuan Fault controlled the distribution of basalt. Our results, merged with a review of the Cenozoic tectonic evolution in South China, emphasise the decisive role of the India–Eurasia collision on the tectonics of South China in the Palaeogene and suggest the continuous northward drift of the Philippine Sea Plate and Australian Plate had a substantial effect on South China in the Neogene. This study also proposes a two‐stage tectonic activity model to visualise the Cenozoic tectonic activity acting on the HSA or South China.
Safety parameters of ferromagnetic device during thyroid surgery: Porcine model using continuous neuromonitoring
Authors: Huang Tzu‐Yen , Lin Yi‐Chu , Tseng Hsin‐Yi , Dionigi Gianlorenzo , Kim Hoon Yub , Chai Young Jun , Lu I‐Cheng , Chang Pi‐Ying , Chiang Feng‐Yu , Wu Che‐Wei
Published: June 2020

Background

The ferromagnetic (FM) device is a new surgical energy modality. This study investigated dynamic recurrent laryngeal nerve (RLN) electromyographic (EMG) data to define safety parameters for using FM devices in thyroidectomy.

Methods

Real‐time EMG tracings obtained under continuous neuromonitoring were recorded from 24 RLNs (12 piglets). In the activation study, FM devices were activated at varying distances from the RLN. In the cooling study, FM devices were cooled for varying time intervals, or muscle touch maneuver was performed, before contact with the RLN.

Results

During the FMwand/FMsealer activation, no adverse EMG events occurred at distances of 2 mm or longer. The cooling study revealed no adverse EMG events after 1‐second (FMwand) or 3‐second (FMsealer) intervals or after muscle touch maneuver.

Conclusions

An FM device should be activated at a distance of 2 mm from the RLN and should be adequately cooled before further contact with the RLN. Surgeons can avoid RLN injury by observing standard procedures for using FM devices.
An Endoplasmic Reticulum Stress–MicroRNA‐26a Feedback Circuit in NAFLD
Authors: Xu Haixia , Tian Yan , Tang Dongmei , Zou Sailan , Liu Geng , Song Jiulin , Zhang Guixiang , Du Xiao , Huang Wei , He Bin , Lin Weiqiang , Jin Liang , Huang Wendong , Yang Jiayin , Fu Xianghui
Published: June 2020

Background and Aims

Endoplasmic reticulum (ER) stress is an adaptive response to excessive ER demand and contributes to the development of numerous diseases, including nonalcoholic fatty liver disease (NAFLD), which is hallmarked by the accumulation of lipid within hepatocytes. However, the underlying mechanisms remain elusive. MicroRNAs (miRNAs) play an indispensable role in various stress responses, but their implications in ER stress have not yet been systemically investigated. In this study, we identify a negative feedback loop consisting of hepatic ER stress and miR‐26a in NAFLD pathogenesis.

Approach and Results

Combining miRNA dot blot array and quantitative PCR, we find that miR‐26a is specifically induced by ER stress in liver cells. This induction of miR‐26a is critical for cells to cope with ER stress. In human hepatoma cells and murine primary hepatocytes, overexpression of miR‐26a markedly alleviates chemical‐induced ER stress, as well as palmitate‐triggered ER stress and lipid accumulation. Conversely, deficiency of miR‐26a exhibits opposite effects. Mechanistically, miR‐26a directly targets the eukaryotic initiation factor 2α, a core ER stress effector controlling cellular translation. Intriguingly, miR‐26a is reduced in the livers of patients with NAFLD. Hepatocyte‐specific restoration of miR‐26a in mice significantly mitigates high‐fat diet–induced ER stress and hepatic steatosis. In contrast, deficiency of miR‐26a in mice exacerbates high‐fat diet–induced ER stress, lipid accumulation, inflammation and hepatic steatosis.

Conclusions

Our findings suggest ER stress–induced miR‐26a up‐regulation as a regulator for hepatic ER stress resolution, and highlight the ER stress/miR‐26a/eukaryotic initiation factor 2α cascade as a promising therapeutic strategy for NAFLD.
Exploratory analysis of intensified conditioning as first line treatment for patients with high risk multiple myeloma
Authors: Bommier Côme , Talbot Alexis , Harel Stéphanie , Cuccuini Wendy , Gérard Laurence , Arnulf Bertrand
Published: June 2020

Multiple myeloma has extremely heterogeneous outcomes. Among prognostic factors, t(4;14) and del(17p) are rare oncogenic events associated with very poor prognosis. In an exploratory case‐control study, we compared the combination of Busulfan‐Melphalan or TBI‐Melphalan with high dose Melphalan as a conditioning regimen in a series of 48 patients with del(17p) or t(4;14). These regimens were preceded by a Bortezomib‐containing induction. Progression‐free survival (PFS) was the primary endpoint whereas overall survival (OS) and complete response (CR) rate were the secondary endpoints. Twenty consecutive cases of high‐risk myeloma received a reinforced conditioning regimen of Busulfan 0.8 mg/kg x4/j IV from day‐6 to day‐3 pre‐ graft (BuMel) or total body irradiation (TBI) 12 Gy (TbiMel), having received Melphalan 140 mg/m2 at day‐2 pre‐graft. These cases were matched to 28 controls treated with Melphalan 200 mg/m2 at day‐2 (Mel200). After intensification ± consolidation, with a median follow‐up of 6.3 years, the CR rate was higher in the BuMel/TbiMel group (65% vs 50%, P = .006). No differences were observed between both groups in terms of PFS and OS (P = .96). PFS in patients with a del(17p) mutation tended to be superior in the BuMel/TbiMel group. Our exploratory study shows that reinforcing the intensification regimen with Busulfan or TBI does not seem to improve the prognosis associated to t(4;14) and del(17p) abnormalities.
Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T‐cell leukemia/lymphoma
Authors: Yanagida Eriko , Miyoshi Hiroaki , Takeuchi Mai , Yoshida Noriaki , Nakashima Kazutaka , Yamada Kyohei , Umeno Takeshi , Shimasaki Yasumasa , Furuta Takuya , Seto Masao , Ohshima Koichi
Published: June 2020

The interaction of CD47 and signal‐regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T‐cell leukemia/lymphoma (ATLL) has not been well‐documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non‐neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD‐L1 (miPD‐L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253‐0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.
Impulse noise reduction using hybrid neuro‐fuzzy filter with improved firefly algorithm from X‐ray bio‐images
Authors: Pugalenthi R. , Oliver A. Sheryl , Anuradha M.
Published: June 2020

Noise filtering performance in medical images is improved using a neuro‐fuzy network developed with the combination of a post processor and two neuro‐fuzzy (NF) filters. By the fact, the Sugeno‐type is found to be less accurate during impulse noise reduction process. In this paper, we propose an improved firefly algorithm based hybrid neuro‐fuzzy filter in both the NF filters to improve noise reduction performance. The proposed noise reduction system combines the advantages of the neural, fuzzy and firefly algorithms. In addition, an improved version of firefly algorithm called searching diversity based particle swarm firefly algorithm is used to reduce the local trapping problem as well as to determine the optimal shape of membership function in fuzzy system. Experimental results show that the proposed filter has proved its effectiveness on reducing the impulse noise in medical images against different impulse noise density levels.
Behavior of Gammarus aequicauda (Crustacea, Amphipoda) during predation on Artemia (Crustacea, Anostraca): New experimental results
Authors: Shadrin Nickolai , Yakovenko Vladimir , Anufriieva Elena
Published: June 2020

Gammarus aequicauda and Artemia spp. are abundant crustacean species in Crimean hypersaline lakes. G. aequicauda preys on Artemia but there was no quantitative data on this before the current study. Predation of G. aequicauda on adult Artemia was studied in experiments with two different approaches evaluating (a) the time balance of the feeding process and (b) the grazing intensity. The threshold prey concentration, when consumption began to increase with increasing concentration, was approximately 15 ind./L in 200‐ml vessels and about 5 ind./L in 500‐ml vessels. When the Artemia abundance reached 20–25 ind./L, there was no further influence on the gammarid consumption rate. There was a significant negative correlation between the consumption rate of gammarids and Artemia abundance. According to study results, an individual G. aequicauda may eat up to 20–24 Artemia/day. Our study suggests that (a) G. aequicauda is an omnivorous species and can significantly suppress populations of its prey. (b) The two experimental approaches used to study the feeding of gammarids on Artemia produced similar results, and both may be used to quantitatively assess relations in a “prey–predator” system. (c) The abundance of predators and prey, as well as the experimental vessel volume, may influence the feeding rate. (d) The presence of plant food resources such as the leaves of Ruppia does not influence on the predatory feeding rate of G. aequicauda. (e) The rate of prey consumption by G. aequicauda is not constant and depends nonlinearly on prey and predator abundance. (f) Cannibalism occurs in the presence of plant resources only, but not in the presence of Artemia. (g) Other gammarids react to the capture of Artemia by one of them. They swim up to the successful individual and try to take some part of the prey.
The melatonin receptor antagonist luzindole induces the activation of cellular stress responses and decreases viability of rat pancreatic stellate cells
Authors: Estaras Matias , Marchena Ana M. , Fernandez‐Bermejo Miguel , Mateos Jose M. , Vara Daniel , Roncero Vicente , Salido Gines M. , Gonzalez Antonio
Published: June 2020

In this study, we have examined the effects of luzindole, a melatonin receptor‐antagonist, on cultured pancreatic stellate cells. Intracellular free‐Ca2+ concentration, production of reactive oxygen species (ROS), activation of mitogen‐activated protein kinases (MAPK), endoplasmic reticulum stress and cell viability were analyzed. Stimulation of cells with the luzindole (1, 5, 10 and 50 μm) evoked a slow and progressive increase in intracellular free Ca2+ ([Ca2+]i) towards a plateau. The effect of the compound on Ca2+ mobilization depended on the concentration used. Incubation of cells with the sarcoendoplasmic reticulum Ca2+‐ATPase inhibitor thapsigargin (1 μm), in the absence of Ca2+ in the extracellular medium, induced a transient increase in [Ca2+]i. In the presence of thapsigargin, the addition of luzindole to the cells failed to induce further mobilization of Ca2+. Luzindole induced a concentration‐dependent increase in ROS generation, both in the cytosol and in the mitochondria. This effect was smaller in the absence of extracellular Ca2+. In the presence of luzindole the phosphorylation of p44/42 and p38 MAPKs was increased, whereas no changes in the phosphorylation of JNK could be noted. Moreover, the detection of the endoplasmic reticulum stress‐sensor BiP was increased in the presence of luzindole. Finally, viability was decreased in cells treated with luzindole. Because cellular membrane receptors for melatonin have not been detected in pancreatic stellate cells, we conclude that luzindole could exert direct effects that are not mediated through its action on melatonin membrane receptors.
A Drug Holiday Reduces the Frequency and Severity of Medication-Related Osteonecrosis of the Jaw in a Minipig Model
Authors: Otto Sven , Pautke Christoph , Arens Daniel , Poxleitner Philipp , Eberli Ursula , Nehrbass Dirk , Zeiter Stephan , Stoddart Martin J
Published: June 2020

Treatment of medication-related osteonecrosis of the jaw (MRONJ) is challenging and no clear consensus has been achieved. This study investigated preventive measures recommended for tooth extractions under antiresorptive (AR) treatment and the role of discontinuation of AR therapy to avoid the onset of MRONJ in a minipig model. Thirty-six Göttingen minipigs were divided into four groups. Group 1 (negative control): tooth extractions but no zoledronate (ZOL). Group 2 (positive control): weekly ZOL infusions for 12 weeks followed by tooth extractions without wound management followed by 8 weeks of ZOL treatment. Group 3: weekly ZOL infusions for 12 weeks followed by tooth extractions; surgical wound management (resection of sharp bone edges, mucoperiosteal coverage); and continuation of ZOL infusions for 8 weeks plus antibiotic treatment. Group 4: 12 weeks of ZOL infusions followed by a drug holiday for 6 weeks. Tooth extractions with preventive wound management followed by antibiotic treatment for 8 weeks but no ZOL infusions. Jawbones were subjected to macroscopic, radiological (CT and micro-CT) and histopathological investigations. No clinical cases of MRONJ were observed in the negative group, in the positive control all animals developed MRONJ. Group 3 developed MRONJ in 83% of cases. With a drug holiday, 40% developed MRONJ in areas of tooth extraction. This is the first large animal model that reduces the occurrence of MRONJ following tooth extraction by the implementation of a drug holiday combined with antibiotic prophylaxis and smoothening of sharp bony edges. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..
A note on 3‐partite graphs without 4‐cycles
Authors: Lv Zequn , Lu Mei , Fang Chunqiu
Published: June 2020

Let be a cycle of order 4. Write for the maximum number of edges in a balanced 3‐partite graph whose vertex set consists of three parts, each has vertices that have no subgraph isomorphic to . In this paper, we show that , where and is a prime number. Note that from Tait and Timmons's works. Since for every integer , one can find a prime such that , we obtain that .
Challenging the role of challenge in intensive short‐term dynamic psychotherapy for social anxiety disorder: A randomized controlled trial
Authors: Rahmani Fateh , Abbass Allan , Hemmati Azad , Ghaffari Niloofar , Rezaei Mirghaed Sahar
Published: June 2020

Objectives

Intensive short‐term dynamic psychotherapy (ISTDP) requires the technique of challenge to defenses when treating resistant patients. As the technique of challenge is difficult for some therapists to practice, it leads us to question whether challenge can be replaced by clarification of defenses without losing treatment effectiveness. This study compared ISTDP with two different technical emphases while treating social anxiety disorder (SAD).

Method

Forty‐two subjects with DSM‐5 SAD were randomly assigned to either a waitlist control, 10 sessions of ISTDP with the use of challenge or 10 sessions of ISTDP without the use of challenge.

Results

ISTDP led to significant, sustained symptom reduction on the Liebowitz Social Anxiety Scale (LSAS‐SR) compared with the control group. There were no significant outcome differences between standard ISTDP and ISTDP where challenge was restricted.

Conclusion

ISTDP is efficacious for SAD. ISTDP may be effective for SAD without the use of challenge elements.
Nail‐biting, scab‐picking, and tattooing as nonsuicidal self‐injury (NSSI): A deviant case series analysis of the proposed NSSI disorder diagnostic criteria
Authors: Mann Adam J. D. , Van Voorhees Elizabeth E. , Patel Tapan A. , Wilson Sarah M. , Gratz Kim L. , Calhoun Patrick S. , Beckham Jean C. , Kimbrel Nathan A.
Published: June 2020

Objective

This study explored the boundaries of the proposed diagnostic criteria for nonsuicidal self‐injury disorder (NSSID) as outlined in the Conditions for Further Study section of the Diagnostic and Statistical Manual, Fifth Edition. We sought to falsify the exclusion of certain NSSI behaviors from a diagnosis of NSSID (Criterion D), arguing that these exclusions are inconsistent with the broader phenomenology of the disorder outlined in the other criteria. 

Method

We describe three case studies involving NSSI (Case 1: scab‐picking; Case 2: nail‐biting; Case 3: tattooing) that cannot be diagnosed as NSSID because the behaviors are explicitly listed in Criterion D.

Results

Despite exclusion as a relevant NSSI behavior per Criterion D, each examined behavior is consistent with the intentionality, functionality, and distress/impairment of NSSID that represent core features of the disorder.

Conclusion

The case studies presented here suggest that Criterion D should be revised or removed from the NSSID criteria.
Pain centrality mediates pain self‐efficacy and symptom severity among individuals reporting chronic pain
Authors: Sucher Jillian , Quenstedt Stella R. , Parnes McKenna F. , Brown Adam D.
Published: June 2020

Chronic pain is consistently associated with the presence of mental health disorders. Although previous research has shown relations between low levels of self‐efficacy with chronic pain severity as well as comorbid mental health symptoms, the link between self‐efficacy and mental health symptoms in chronic pain is not well understood. This study examined whether pain centrality, the extent to which pain is viewed as central to self‐identity, may underlie these associations. Individuals with a diagnosis of chronic pain (N = 89) recruited through MTurkcompleted self‐report measures including demographics, self‐efficacy, pain centrality, pain severity, depression, and anxiety. Pain severity was associated with higher levels of pain centrality, depression, anxiety, and lower levels of self‐efficacy. Path analysis demonstrated pain centrality significantly mediated the relationship between self‐efficacy and pain severity, depression, and anxiety. Future studies would benefit from testing whether modifying pain centrality beliefs shift perceptions of control as well as pain and psychological outcomes.
Characteristics of drug‐facilitated sexual assault in Spain
Authors: Quintana José Manuel , García‐Maroto Álvaro , Moreno Olga , Manzanero Antonio L.
Published: June 2020

The aim of this study consisted in analysing the cases of drug‐facilitated sexual assault— chemical submission—from 2008 to 2017. A total of 240 cases registered during this period within the territorial area of the Spanish Civil Guard were analysed. Results show an increasing incidence of sexual assault cases that are drug‐facilitated in order to annul the will of the victim, or at least that there is a greater awareness to report these cases. From the analyses carried out, distinctive characteristics of this type of sexual offences were observed with respect to other modalities, in the sense that they are linked to leisure situations (at night, on weekends and holiday periods) although the place of commission is fundamentally the victim's or the perpetrator's residence. The profile of the victim is that of a young woman, of legal age (with a mean age of 25 years) and Spanish, although foreign women are also vulnerable victims. When the victim is male, the mean age decreases notably (20 years) with a higher incidence among minors. The aggressor is eminently male, older (around 30 years) and also Spanish. Databases can be a good starting point to frame the phenomenon, elucidating some of the main variables that intervene in these crimes, such as the moment and place of commission, as well as those persons most inclined to suffer them and, in the opposite pole, those most likely to carry out this type of criminal act.
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre
Authors: Ranganath Lakshminarayan R. , Milan Anna M. , Hughes Andrew T. , Khedr Milad , Davison Andrew S. , Wilson Peter J. , Dillon Jane P. , West Elizabeth , Gallagher James A.
Published: June 2020

Background

Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression.

Methods

Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V‐1 (pre‐baseline visit), V0 (baseline visit when 2 mg nitisinone was commenced), and yearly at V1, V2, and V3 visits. Photographs were inspected for evolution of ochronotic pigment and also scored categorically to derive eye, ear, and combined ochronosis scores. An ear cartilage biopsy was also carried out at V0 and one year after V3 (V4) and ochronotic pigment was assessed and quantitated. Visits were compared for changes in pigment. Fasting blood and 24‐hour urine samples were collected for measurement of HGA.

Results

There were 80 AKU patients at V0, and 52, 47, and 40 at V1, V2, and V3 in the group with variable numbers (VAR Group) respectively; 23 patients attended once before V0, in the V‐1 visit. Photographs of patients show increase in eye pigment between V‐1 and V0, followed by decrease post‐nitisinone at V1, V2, and V3. Ear and combined ochronosis semiquantitative scoring showed an increase between V‐1 and V0 (P < .01), followed by a decrease at V1, V2, and V3, in the VAR group (P < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease (P < .05).

Conclusions

Nitisinone decreases HGA and partially reverses ochronosis.
Identification of the association of CD28+CD244+ Tc17/IFN‐γ cells with chronic hepatitis C virus infection
Authors: Han Wenzheng , Li Jiajia , Zhou Hongchang , Qian Jing , Tong Zhaowei , Wang Weihong , Zhong Jianfeng , Xue Tao , Chen Qing , Yao Yunliang , Shao Shengwen
Published: June 2020

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T‐cell subsets were confirmed to be closely related to HCV infection such as TCM, TEM, TEMRA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)‐17/interferon (IFN)‐γ producing CD8+ T (Tc17/IFN‐γ) cells that markedly correlate with CD28+CD244+ cells, IL‐17 levels, and HCV RNA in HCV patients. During early treatment with peg‐IFN‐a2a plus ribavirin, the imbalance of these Tc17/IFN‐γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4‐week course of treatment with peg‐IFN‐a2a plus ribavirin and found that the percentage of CD8+CD28+CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+CD244+ T cells were the only CD8+ T‐cell group that secreted both IL‐17 and IFN‐γ in this axis and blockade with anti‐CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+CD244+ Tc17/IFN‐γ cells may play an important role in persistent HCV infection.