bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of risk factors and complications associated with atrial fibrillation after oesophagectomy
Authors: Schizas D , Kosmopoulos M , Giannopoulos S , Giannopoulos S , Kokkinidis D G , Karampetsou N , Papanastasiou C A , Rouvelas I , Liakakos T
Published: March 2019

Background

Oesophagectomy is associated with high morbidity and mortality rates. New-onset atrial fibrillation (AF) is a frequent complication following oesophagectomy. Several studies have explored whether new-onset AF is associated with adverse events after oesophagectomy.

Methods

This review was performed according to PRISMA guidelines. Eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 25 November 2018. A meta-analysis was conducted with the use of random-effects modelling. The I2 statistic was used to assess for heterogeneity.

Results

In total, 53 studies including 9087 patients were eligible for analysis. The overall incidence of postoperative AF was 16·5 per cent. Coronary artery disease and hypertension were associated with AF, whereas diabetes, smoking and chronic obstructive pulmonary disease were not. Patients with AF had a significantly higher risk of overall postoperative adverse events than those without fibrillation (odds ratio (OR) 5·50, 95 per cent c.i. 3·51 to 8·30), including 30-day mortality (OR 2·49, 1·70 to 3·64), anastomotic leak (OR 2·65, 1·53 to 4·59) and pneumonia (OR 3·42, 2·39 to 4·90).

Conclusion

Postoperative AF is frequently observed in patients undergoing oesophagectomy for cancer. It is associated with an increased risk of death and postoperative complications.
When both Km and Vmax are altered, Is the enzyme inhibited or activated?
Authors: Silverstein Todd P.
Published: March 2019

Enzyme activators lower Km (the Michaelis constant) and/or raise Vmax (the asymptotic reaction velocity at infinite substrate concentration); conversely, inhibitors raise Km and/or lower Vmax. But what if an effector moves both Km and Vmax in the same direction? Uncompetitive inhibitors, which decrease both Km and Vmax by the same factor, are the most common example of this. A less well‐known example occurs often when crowding agents are added to the buffer in order to mimic the environment commonly encountered in vivo. Crowding agents tested on different enzymes have been shown to have every conceivable effect on Km or Vmax, causing them to rise, fall, or stay the same. In this article, a mathematical analysis is presented allowing biochemists to judge whether an effector that causes Km and Vmax to both move in the same direction serves as an inhibitor, an activator, or most surprising, as both. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):446–449, 2019.
Hope and challenge: Precision medicine in bladder cancer
Authors: Su Hongwei , Jiang Haitao , Tao Tao , Kang Xing , Zhang Xu , Kang Danyue , Li Shucheng , Li Chengxi , Wang Haifeng , Yang Zhao , Zhang Jinku , Li Chong
Published: March 2019

Bladder cancer (BC) is a complex disease and could be classified into nonmuscle‐invasive BC (NMIBC) or muscle‐invasive BC (MIBC) subtypes according to the distinct genetic background and clinical prognosis. Until now, the golden standard and confirmed diagnosis of BC is cystoscopy and the major problems of BC are the high rate of recurrence and high costs in the clinic. Recent molecular and genetic studies have provided perspectives on the novel biomarkers and potential therapeutic targets of BC. In this article, we provided an overview of the traditional diagnostic approaches of BC, and introduced some new imaging, endoscopic, and immunological diagnostic technology in the accurate diagnosis of BC. Meanwhile, the minimally invasive precision treatment technique, immunotherapy, chemotherapy, gene therapy, and targeted therapy of BC were also included. Here, we will overview the diagnosis and therapy methods of BC used in clinical practice, focusing on their specificity, efficiency, and safety. On the basis of the discussion of the benefits of precision medicine in BC, we will also discuss the challenges and limitations facing the non‐invasive methods of diagnosis and precision therapy of BC. The molecularly targeted and immunotherapeutic approaches, and gene therapy methods to BC treatment improved the prognosis and overall survival of BC patients.
Nucleophilic Substitution of Aliphatic Fluorides via Pseudohalide Intermediates
Authors: Jaiswal Amit K. , Prasad Pragati K. , Young Rowan D.
Published: March 2019

A method for aliphatic fluoride functionalization with a variety of nucleophiles has been reported. Carbon–fluoride bond cleavage is thermodynamically driven by the use of silylated pseudohalides TMS‐OMs or TMS‐NTf2, resulting in the formation of TMS‐F and a trapped aliphatic pseudohalide intermediate. The rate of fluoride/pseudohalide exchange and the stability of this intermediate are such that little rearrangement is observed for terminal fluoride positions in linear aliphatic fluorides. The ability to convert organofluoride positions into pseudohalide groups allows facile nucleophilic attack by a wide range of nucleophiles. The late introduction of the nucleophiles also allows for a wide range of functional‐group tolerance in the coupling partners. Selective alkyl fluoride mesylation is observed in the presence of other alkyl halides, allowing for orthogonal synthetic strategies.
Electrocatalysis of a Europium‐Dependent Bacterial Methanol Dehydrogenase with Its Physiological Electron‐Acceptor Cytochrome cGJ
Authors: Kalimuthu Palraj , Daumann Lena J. , Pol Arjan , Op den Camp Huub J. M. , Bernhardt Paul V.
Published: March 2019

We report the first electrochemical study of a lanthanoid‐dependent methanol dehydrogenase (Eu‐MDH) from the acidophilic verrucomicrobial methanotroph Methylacidiphilum fumariolicum SolV with its own physiological cytochrome cGJ electron acceptor. Eu‐MDH harbours a redox active 2,7,9‐tricarboxypyrroloquinoline quinone (PQQ) cofactor which is non‐covalently bound but coordinates trivalent lanthanoid elements including Eu3+. Eu‐MDH and the cytochrome were co‐adsorbed with the biopolymer chitosan and cast onto a mercaptoundecanol (MU) monolayer modified Au working electrode. Cyclic voltammetry of cytochrome cGJ reveals a well‐defined quasi‐reversible FeIII/II redox couple at +255 mV vs. NHE at pH 7.5 and this response is pH independent. The reversible one‐electron response of the cytochrome cGJ transforms into a sigmoidal catalytic wave in the presence of Eu‐MDH and its substrates (methanol or formaldehyde). The catalytic current was pH‐dependent and pH 7.3 was found to be optimal. Kinetic parameters (pH dependence, activation energy) obtained by electrochemistry show the same trends as those obtained from an artificial phenazine ethosulfate/dichlorophenol indophenol assay.
Reactions of GeCl2 with the Thiolate LiSC(SiMe3)3: From thf Activation to Insertion of GeCl2 Molecules into C−S Bonds
Authors: Kunz Tanja , Schrenk Claudio , Schnepf Andreas
Published: March 2019

The reaction system GeCl2⋅dioxane/LiSTsi (Tsi=C(SiMe3)3) opens a fruitful area in germanium chemistry, depending on the stoichiometry and solvent used during the reaction. For example, the reaction of GeCl2⋅dioxane in toluene with two equivalents of the thiolate gives the expected germylene Ge(STsi)2 in excellent yield. This germylene readily reacts with hydrogen and acetylene, however, in a non‐selective way. By using an excess amount of the thiolate and toluene as the solvent, the germanide [Ge(STsi)3][Li(thf)] is obtained. Performing the same reaction in thf leads to a C−H activation of thf to give (H7C4O)Ge[STsi](μ2‐S)2Ge[STsi]2, in which the thf molecule is still intact. Using a sub‐stoichiometric amount of the thiolate leads to the heteroleptic compound [ClGe(STsi)]2 and to the insertion product (thf)Ge[S‐GeCl2‐Tsi]2, in which additional GeCl2 molecules insert into the C−S bonds of Ge(STsi)2. The synthesis and the experimentally determined structures of all compounds are presented together with first reactivity studies of Ge(STsi)2.
Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins
Authors: Laporte Fanny A. , Lebrun Colette , Vidaud Claude , Delangle Pascale
Published: March 2019

Some phosphoproteins such as osteopontin (OPN) have been identified as high‐affinity uranyl targets. However, the binding sites required for interaction with uranyl and therefore involved in its toxicity have not been identified in the whole protein. The biomimetic approach proposed here aimed to decipher the nature of these sites and should help to understand the role of the multiple phosphorylations in UO22+ binding. Two hyperphosphorylated cyclic peptides, pS168 and pS1368 containing up to four phosphoserine (pSer) residues over the ten amino acids present in the sequences, were synthesized with all reactions performed in the solid phase, including post‐phosphorylation. These β‐sheet‐structured peptides present four coordinating residues from four amino acid side chains pointing to the metal ion, either three pSer and one glutamate in pS168 or four pSer in pS1368. Significantly, increasing the number of pSer residues up to four in the cyclodecapeptide scaffolds produced molecules with an affinity constant for UO22+ that is as large as that reported for osteopontin at physiological pH. The phosphate‐rich pS1368 can thus be considered a relevant model of UO22+ coordination in this intrinsically disordered protein, which wraps around the metal ion to gather four phosphate groups in the UO22+ coordination sphere. These model hyperphosphorylated peptides are highly selective for UO22+ with respect to endogenous Ca2+, which makes them good starting structures for selective UO22+ complexation.
Cyclic(Alkyl)(Amino)Carbene (CAAC)‐Supported Zn Alkyls: Synthesis, Structure and Reactivity in Hydrosilylation Catalysis
Authors: Bruyere Jean‐Charles , Specklin David , Gourlaouen Christophe , Lapenta Rosita , Veiros Luis F. , Grassi Alfonso , Milione Stefano , Ruhlmann Laurent , Boudon Corinne , Dagorne Samuel
Published: March 2019

The reactivity of ZnII dialkyl species ZnMe2 with a cyclic(alkyl)(amino)carbene, 1‐[2,6‐bis(1‐methylethyl)phenyl]‐3,3,5,5‐tetramethyl‐2‐pyrrolidinylidene (CAAC, 1), was studied and extended to the preparation of robust CAAC‐supported ZnII Lewis acidic organocations. CAAC adduct of ZnMe2 (2), formed from a 1:1 mixture of 1 and ZnMe2, is unstable at room temperature and readily undergoes a CAAC carbene insertion into the Zn−Me bond to produce the ZnX2‐type species (CAAC‐Me)ZnMe (3), a reactivity further supported by DFT calculations. Despite its limited stability, adduct 2 was cleanly ionized to robust two‐coordinate (CAAC)ZnMe+ cation (5+) and derived into (CAAC)ZnC6F5+ (7+), both isolated as B(C6F5)4− salts, showing the ability of CAAC for the stabilization of reactive [ZnMe]+ and [ZnC6F5]+ moieties. Due to the lability of the CAAC−ZnMe2 bond, the formation of bis(CAAC) adduct (CAAC)2ZnMe+ cation (6+) was also observed and the corresponding salt [6][B(C6F5)4] was structurally characterized. As estimated from experimental and calculations data, cations 5+ and 7+ are highly Lewis acidic species and the stronger Lewis acid 7+ effectively mediates alkene, alkyne and CO2 hydrosilylation catalysis. All supporting data hints at Lewis acid type activation–functionalization processes. Despite a lower energy LUMO in 5+ and 7+, their observed reactivity is comparable to those of N‐heterocyclic carbene (NHC) analogues, in line with charge‐controlled reactions for carbene‐stabilized ZnII organocations.
The Role of Electrochemistry in Future Dynamic Bio‐Refineries: A Focus on (Non‐)Kolbe Electrolysis
Authors: Palkovits Stefan , Palkovits Regina
Published: March 2019

The vision of a circular economy with closed carbon dioxide cycles is inevitably connected to a change of raw materials. Non‐edible biomass is an attractive carbon source for chemical industry. Brought together with renewable energy, the electrocatalytic transformation of biomass‐based feedstocks enables to directly integrate renewable electrical energy into chemical value chains. Considering the major role of natural carboxylic acids, the well‐known Kolbe and non‐Kolbe electrolysis attract increasing interest as versatile tools to valorize renewable feedstocks providing access to both biofuels and bulk or fine chemicals. They allow via decarboxylation access either to the corresponding dimerization product or the terminal alkene. Here, the electrochemical valorization of biomass is discussed with special emphasis on the possible role of (non‐)Kolbe electrolysis in a future electrified biorefinery.
Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial
Authors: Guimarães Patricia O. , Pokorney Sean D. , Lopes Renato D. , Wojdyla Daniel M. , Gersh Bernard J. , Giczewska Anna , Carnicelli Anthony , Lewis Basil S. , Hanna Michael , Wallentin Lars , Vinereanu Dragos , Alexander John H. , Granger Christopher B.
Published: March 2019

Background

The optimal anticoagulation strategy for patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) replacement or native valve repair remains uncertain.

Hypothesis

We evaluated the safety and efficacy of apixaban vs warfarin in patients with AF and a history of BPV replacement or native valve repair.

Methods

Using data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) (n = 18 201), a randomized trial comparing apixaban with warfarin in patients with AF, we analyzed the subgroup of patients (n = 251) with prior valve surgery. We contacted sites by telephone to obtain additional data about prior valve surgery. Full data were available for 156 patients. The primary efficacy endpoint was stroke/systemic embolism. The primary safety endpoint was major bleeding. Treatment groups were compared using a Cox regression model.

Results

In ARISTOTLE, 104 (0.6%) patients had a history of BPV replacement (n = 73 [aortic], n = 26 [mitral], n = 5 [mitral and aortic]) and 52 (0.3%) had a history of valve repair (n = 50 [mitral], n = 2 [aortic]). Among patients with BPVs, 55 were randomized to apixaban and 49 to warfarin. Among those with a history of native valve repair, 32 were randomized to apixaban and 20 to warfarin. Overall clinical event rates were low, with no significant differences between apixaban and warfarin for any outcomes.

Conclusions

In patients with AF and a history of BPV replacement or repair, the safety and efficacy of apixaban compared with warfarin was consistent with results from ARISTOTLE. These data suggest that apixaban may be reasonable for patients with BPVs or prior valve repair, though future larger randomized trials are needed.

ClinicalTrials.gov

NCT00412984.
H2O2‐Responsive Organosilica‐Doxorubicin Nanoparticles for Targeted Imaging and Killing of Cancer Cells Based on a Synthesized Silane‐Borate Precursor
Authors: Xu Yanhui , Shi Wen , Li Hongyu , Li Xiaohua , Ma Huimin
Published: March 2019

Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane‐borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol‐containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si‐Dox@HA nanoparticles with the ability to target CD44‐overexpressing cancer cells. The Si‐Dox@HA nanoparticles exhibited H2O2‐responsive release of about 80 % Dox and displayed seven‐fold selectivity for killing cancer cells over normal cells, relative to Dox and Si‐Dox nanoparticles. Moreover, these Si‐Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44‐overexpressing cancer cells.
Bridging the demand and the offer in data science
Authors: Belloum Adam S.Z. , Koulouzis Spiros , Wiktorski Tomasz , Manieri Andrea
Published: March 2019

During the last several years, we have observed an exponential increase in the demand for Data Scientists in the job market. As a result, a number of trainings, courses, books, and university educational programs (both at undergraduate, graduate and postgraduate levels) have been labeled as “Big data” or “Data Science”; the fil‐rouge of each of them is the aim at forming people with the right competencies and skills to satisfy the business sector needs. In this paper, we report on some of the exercises done in analyzing current Data Science education offer and matching with the needs of the job markets to propose a scalable matching service, ie, COmpetencies ClassificatiOn (E‐CO‐2), based on Data Science techniques. The E‐CO‐2 service can help to extract relevant information from Data Science–related documents (course descriptions, job Ads, blogs, or papers), which enable the comparison of the demand and offer in the field of Data Science Education and HR management, ultimately helping to establish the profession of Data Scientist.
The Effect of Crucible Rotation and Crucible Size in Top‐Seeded Solution Growth of Single‐Crystal Silicon Carbide
Authors: Horiuchi Takashi , Wang Lei , Sekimoto Atsushi , Okano Yasunori , Yamamoto Takuya , Ujihara Toru , Dost Sadik
Published: March 2019

The top‐seeded solution growth method is a promising technique for growing high‐quality silicon carbide single crystal. Some inherent issues in this growth process, such as morphological instability, polycrystalline growth, and low growth rate, should be clarified. A high temperature difference between the seed and the crucible wall in this system is needed to enhance growth. However, such a high temperature gradient makes the radial growth rate profile non‐uniform due to the effect of Marangoni convection below the seed crystal, which leads to poor crystal quality. In the present work, the effects of crucible size and crucible rotation are numerically investigated to minimize the effect of Marangoni convection. The possibilities of the occurrence of growth‐rate non‐uniformity and undesired impurity incorporation are examined. A smaller crucible (in radius) leads to a more uniform growth rate profile. However, it gives rise to a higher possibility of impurity incorporation. It is also predicted that crucible rotation is ineffective in suppressing the Marangoni flow near the seed edge. This leads to a flow stagnation in the center of the melt, and consequently, it does not enhance the carbon transport below the seed. It also does not reduce the possibility of undesired impurity incorporation.
High‐Performance Jet Fuels Derived from Bio‐Based Alkenes by Iron‐Catalyzed [2+2] Cycloaddition
Authors: Morris David M. , Quintana Roxanne L. , Harvey Benjamin G.
Published: March 2019

A series of high‐performance cycloparaffinic fuels have been generated by [2+2] cycloaddition of the bio‐derived alkenes 1‐hexene, isoprene, and 1‐pentene, catalyzed by a low‐valent iron pyridine(diimine) complex [(MePDI)Fe(N2)2(μ‐N2)] [MePDI=N,N′‐(2,6‐pyridinediyldiethylidyne)bis(2,6‐dimethylbenzenamine)]. Reactions with 1‐pentene and 1‐hexene resulted in 85 % selectivity to 1,2‐cyclobutanes, and 12 % selectivity to acyclic alkenes generated by β‐hydride elimination. Self‐dimerization of isoprene was sluggish and generated heavier oligomer products, but cross‐dimerization of isoprene with 1‐hexene afforded primarily a 1,3‐cyclobutane product, along with isomers of acyclic C11 mixed dimers. Hydrocarbon mixtures were hydrogenated and fractionally distilled to yield finished fuel mixtures in overall yields of 83–93 % at the multigram scale. The fuels exhibited densities ranging between 0.767 and 0.783 g mL−1, and net heats of combustion (NHOC) of up to 120.6 kBtu gal−1 (43.8 MJ kg−1). These values are higher than conventional synthetic paraffinic kerosenes owing to the higher density and ring strain afforded by the cyclobutane rings. The fuel mixtures also exhibited extremely low viscosities ranging from 2.38 to 4.78 mm2 s−1 at −20 °C, due in part to the presence of the acyclic dimers. The excellent fuel properties of the product mixtures, selectivity for dimer products, high yields, and the ability to use simple bio‐derived alkenes as substrates, make the [Fe]‐catalyzed [2+2] cycloaddition of unactivated alkenes a compelling route to the synthesis of sustainable high‐performance fuels.
Diabetic lung, an underrated complication from restrictive functional pattern to pulmonary hypertension
Authors: Fuso Leonello , Pitocco Dario , Antonelli‐Incalzi Raffaele
Published: March 2019

In patients with type 1 and type 2 diabetes mellitus (DM), respiratory function abnormalities have been reported with regard to lung volumes, pulmonary diffusing capacity, control of ventilation, bronchomotor tone, and neuroadrenergic bronchial innervation. Indeed, the decrease in lung volumes and the impairment of diffusing capacity might have important clinical implications. Furthermore, there is an increasing evidence of a link between DM and pulmonary hypertension (PH) related to an involvement of the pulmonary vascular structures. These findings support the view of the lung as target organ in DM. In this paper, we briefly describe the main derangements of the respiratory system in DM and the inherent mechanisms.
A strong colonizer rules the trematode guild in an intertidal snail host
Authors: Alda Pilar , Bonel Nicolás , Cazzaniga Néstor J. , Martorelli Sergio R. , Lafferty Kevin D.
Published: March 2019

We examined the extent to which supply‐side, niche, and competition theories and concepts help explain a trematode community in which one species comprises 87% of the trematode individuals, and the remaining 15 species each have <3%. We collected and dissected the common and wide‐ranging snail host Heleobia australis over four seasons from three distinct habitats from the intertidal area of the Bahía Blanca estuary, Argentina. Inside a snail, trematodes interact with each other with outcomes that depend on facilitation, competition, and preemption, suggesting that dominant species should be common. The abundant trematode species, Microphallus simillimus, is a weak competitor, but has life‐history traits and strategies associated with higher colonization ability that could increase its probability of invading the host first, allowing it to preempt the rare species. Rather than segregate by habitat, trematode species aggregated in pans during the summer where dominant trematode species often excluded subordinate ones. Despite losses to competition, and a lack of niche partitioning, M. simillimus ruled this species‐rich trematode guild through strong recruitment and (potentially) preemption. Therefore, extremely skewed species abundance distributions, like this one, can derive from extremely skewed colonization abilities.
Influence of Carbon Supports on Palladium Nanoparticle Activity toward Hydrodeoxygenation and Aerobic Oxidation in Biomass Transformations
Authors: Espinosa Juan C. , Contreras Rubén Castro , Navalón Sergio , Rivera‐Cárcamo Camila , Álvaro Mercedes , Machado Bruno F. , Serp Philippe , Garcia Hermenegildo
Published: March 2019

Three palladium catalysts at similar loadings supported on few‐layers graphene (FLG), carbon nanotubes (CNT) and carbon nanofibers (CNF) have been prepared by wet impregnation of palladium nitrate with the purpose of determine the influence of the support on Pd catalytic activity. The supports and catalysts have been characterized by chemical analysis, Raman spectroscopy, XRD, electron microscopy and XPS. The average Pd particle size depends on the carbon support, ranging from 1.6 nm for CNF to 2.6 nm for FLG. The catalytic activity of these catalysts was evaluated for two different reactions of interest for biomass transformations, namely hydrodeoxygenation of vanillin to 2‐methoxy‐4‐methyl‐phenol (creosol) that requires a bifunctional catalyst with hydrogenating and Lewis acid sites, and aerobic oxidation of 5‐hydroxymethylfurfural to 2,5‐furandicarboxylic acid. Both compounds have application either as food flavouring additive and polyester co‐monomer. For the two reactions the activity order of the fresh catalyst was Pd/FLG > Pd/CNF > Pd/CNT, indicating that FLG contributes favorably to the activity in spite of the larger Pd size of the nanoparticles on this support, a fact that has been attributed to the interaction with the prismatic planes on where Pd nanoparticles are located.
Concise Synthesis of a New Chiral Cyclopentenone Building Block for Prostaglandins and their Derivatives
Authors: Żurawiński Remigiusz , Łukasik Beata
Published: March 2019

(4R,5R)‐4,5‐O‐isopropylidene‐2‐(dimethoxyphosphoryl)cyclopen‐2‐enone was obtained in enantiomerically pure form in four steps starting from commercially available 2,3‐O‐isopropylidene‐D‐erythronolactone. The key steps involved are diastereoselective lactone ring opening leading in a one‐pot procedure to the ε‐silyloxy Weinreb‐type amide, and the cyclopentenone ring formation by the rhodium catalyzed carbenoid cyclization of the corresponding ε‐silyloxy‐α‐diazo‐β‐ketophosphonate followed by the elimination of tert‐butyldimethylsilanol. During the synthetic study on the construction of the cyclopentanone ring by the intramolecular nucleophilic substitution reaction of an anion generated from ε‐bromo‐β‐ketophosphonate, the formation of cyclopropane derivative was observed. This stereochemical outcome was rationalized using quantum chemical calculations.
Investigation of the Influence of Deposition Accuracy of Electrodes on the Electrochemical Properties of Lithium‐Ion Batteries
Authors: Leithoff Ruben , Fröhlich Arian , Dröder Klaus
Published: March 2019

Nowadays, battery production involves the use of cost‐intensive materials and highly complex production processes. The knowledge of interactions between product properties and process parameters is often limited to best‐practice‐experience rather than based on actual quantitative correlations. This work quantifies the influence of electrode deposition accuracy (process parameter) on the electrochemical performance (product property) of large battery cells (discharge capacity >8 Ah). In total, 40 lithium‐ion battery cells with five different deposition error configurations are manufactured and electrochemically tested. The electrochemical results of these tests show a linear decrease in the discharge capacity with a linear increase in the deposition error. The reduced discharge capacity is attributed to the extended nonoverlap of cathode and anode areas as well as the larger travel distances of intercalating ions.
A 17‐Beta‐Hydroxysteroid Dehydrogenase 13 Variant Protects From Hepatocellular Carcinoma Development in Alcoholic Liver Disease
Authors: Yang Jie , Trépo Eric , Nahon Pierre , Cao Qian , Moreno Christophe , Letouzé Eric , Imbeaud Sandrine , Bayard Quentin , Gustot Thierry , Deviere Jacques , Bioulac‐Sage Paulette , Calderaro Julien , Ganne‐Carrié Nathalie , Laurent Alexis , Blanc Jean Frédéric , Guyot Erwan , Sutton Angela , Ziol Marianne , Zucman‐Rossi Jessica , Nault Jean‐Charles
Published: March 2019

Recently, a loss of function variant (rs72613567) in 17‐beta‐hydroxysteroid dehydrogenase 13 (HSD17B13) has been identified as protective of nonalcoholic (NAFLD) and alcoholic liver disease (ALD). However, the role of this single‐nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) is currently unknown. A total of 3,315 European patients with HCC (n = 1,109) or without HCC, but with chronic liver disease (CLD; n = 2,206), from four centers were analyzed either by whole‐exome sequencing (WES; exploratory cohort, 285 HCC) or genotyped for HSD17B13 rs72613567 (validation cohort, 824 HCC and all CLD). We included a control group of 33,337 healthy European individuals from the Exome Aggregation Consortium. We compared distribution of genotype using the chi‐square test and logistic regression. In the exploratory cohort analyzed by WES, frequency of the TA allele of HSD17B13 rs72613567 was significantly decreased in HCC patients compared to healthy controls (P = 1.52 × 10−06). In the validation cohort, frequency of TA allele carriers was also decreased in patients with CLD and without HCC (39%) compared to healthy individuals (47%; P < 0.0001). The protective effect of the TA allele of HSD17B13 rs72613567 was identified in patients with ALD (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.65‐0.82; P < 0.0001), NAFLD (OR = 0.64; 95% CI, 0.49‐0.83; P = 0.0007), and hepatitis C (OR = 0.71; 95% CI, 0.60‐0.85; P = 0.0002). In patients with ALD, the proportion of TA allele carriers with HCC was significantly lower (32%) than in CLD patients without HCC (40%), even after adjustment for age, sex, and fibrosis (OR = 0.64; 95% CI, 0.46‐0.87; P = 0.005). Conclusion: The HSD17B13 rs72613567 loss of function variant is protective of HCC development in patients with ALD.
Patients With Acute on Chronic Liver Failure Grade 3 Have Greater 14‐Day Waitlist Mortality Than Status‐1a Patients
Authors: Sundaram Vinay , Shah Parth , Wong Robert J. , Karvellas Constantine J. , Fortune Brett E. , Mahmud Nadim , Kuo Alexander , Jalan Rajiv
Published: March 2019

Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF‐3) portends low survival without transplantation, which may not be reflected by the Model for End‐Stage Liver Disease‐Sodium (MELD‐Na) score. We compared short‐term waitlist mortality for patients listed status 1a and those with ACLF‐3 at listing. Data were analyzed from the United Network for Organ Sharing database, years 2002‐2014, for 3,377 patients listed status 1a and 5,099 patients with ACLF‐3. Candidates with ACLF were identified based on the European Association for the Study of the Liver Chronic Liver Failure Consortium criteria. MELD‐Na score was treated as a categorical variable of scores <36, 36‐40, and >40. We used competing risks regression to assess waitlist mortality risk. Evaluation of outcomes through 21 days after listing demonstrated a rising trend in mortality among ACLF‐3 patients at 7 days (18.0%), 14 days (27.7%), and 21 days (32.7%) (P < 0.001) compared to a stable trend in mortality among individuals listed as status 1a at 7 days (17.9%), 14 days (19.3%), and 21 days (19.8%) (P = 0.709). Multivariable modeling with adjustment for MELD‐Na category revealed that patients with ACLF‐3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31‐1.61) within 14 days of listing compared to status‐1a candidates. Analysis of the interaction between MELD‐Na category and ACLF‐3 showed that patients with ACLF‐3 had greater risk of 14‐day mortality than status‐1a‐listed patients, across all three MELD‐Na categories. Conclusion: Patients with ACLF‐3 at the time of listing have greater 14‐day mortality than those listed as status 1a, independent of MELD‐Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF‐3.
Association Between Institutional Factors and Long‐Term Survival Following Transjugular Intrahepatic Portosystemic Shunt
Authors: Mah Jeffrey M. , DeWit Yvonne , Djerboua Maya , Menard Alexandre , Booth Christopher M. , Flemming Jennifer A.
Published: March 2019

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure designed to treat portal hypertension. Hospital teaching status is an institutional factor found to be predictive of outcomes following several complex procedures; however, its impact on outcomes following TIPS is unknown. The aim of this study was to determine the association between hospital teaching status and long‐term survival in patients with cirrhosis receiving TIPS. We performed a retrospective population‐based cohort study using linked administrative health data from Ontario, Canada. Adult patients with cirrhosis who received TIPS between January 1, 1998, and December 31, 2016, with follow‐up until December 31, 2017, were included. Hospital teaching status was defined based on hospital participation in the instruction of medical students and/or resident physicians. Liver transplant‐free (LTF) survival was evaluated using Kaplan‐Meier analysis, and overall survival was assessed using competing risks regression analysis, which accounted for hospital clustering. A total of 857 unique patients were included (mean age 57.1 years; 69.1% male). The TIPS procedures were performed in teaching hospitals (84.3%) as well as nonteaching hospitals (15.7%). Median LTF survival was more than twice as long for procedures performed in teaching hospitals compared to nonteaching hospitals (2.2 years versus 0.9 year, respectively; P < 0.001). After adjusting for confounders and clustering, hospital teaching status was not independently associated with mortality (nonteaching subdistribution hazard ratio [sHR], 1.32; 95% confidence interval [CI], 0.97‐1.81; P = 0.08); however, annual hospital procedure volume was (per unit increase sHR, 0.96; 95% CI, 0.93‐0.99; P = 0.003). Conclusion: Hospital procedure volume is associated with long‐term survival following TIPS. These results further support the centralization of TIPS to high‐volume hospitals to improve long‐term outcomes in this population.
The Fish Community Index: A Practical Management Tool for Monitoring and Reporting Estuarine Ecological Condition
Authors: Hallett Chris S , Trayler Kerry M , Valesini Fiona J
Published: March 2019

Indicators of ecological health based on biological communities, including numerous multimetric indices, are used worldwide to assess and report the condition of aquatic ecosystems such as estuaries. Yet, these tools have rarely been applied to support estuary management in Australia. We present a case study of one such multimetric indicator, the Fish Community Index (FCI), which was developed and applied to quantify the ecological condition of estuaries in southwestern Australia (SWA). We outline the rationale, development, and implementation of the FCI for annual monitoring and reporting of the ecological condition of a highly urbanized estuary, highlighting the key research and management outcomes that it has delivered, and evaluating its potential future applications to support estuary management more broadly, both across Australia and internationally. The FCI is founded upon a conceptually simple and scientifically robust rationale and is sensitive to the ecological stressors that affect many estuaries across the region (e.g., hypoxia, algal blooms). Together with an accompanying annual fish monitoring regime, the FCI provides managers with a consistent, robust basis for quantifying and reporting spatiotemporal changes in estuary condition, with easily comprehensible outputs that facilitate communication with stakeholders, ranging from politicians to the general public. We attribute the successful implementation of this management tool to several characteristics, namely 1) support from a long-term, collaborative partnership between managers and researchers; 2) comprehensive testing and validation of the index prior to implementation; 3) a robust, standardized monitoring regime; and 4) sustained resourcing from managers to implement the index as part of a reporting framework. The FCI has also been applied to other SWA estuaries and could provide a platform for more coordinated assessment and reporting of estuarine condition at the bioregional scale, thereby helping to improve the gap in reporting on the biotic integrity of Australian estuaries. Integr Environ Assess Manag 2019;15:726–738. © 2019 SETAC.
When Are Adverse Outcome Pathways and Associated Assays “Fit for Purpose” for Regulatory Decision-Making and Management of Chemicals?
Authors: Coady Katie , Browne Patience , Embry Michelle , Hill Thomas , Leinala Eeva , Steeger Thomas , Maślankiewicz Lidka , Hutchinson Tom
Published: March 2019

There have been increasing demands for chemical hazard and risk assessments in recent years. Chemical companies have expanded internal product stewardship initiatives, and jurisdictions have increased the regulatory requirements for the manufacture and sale of chemicals. There has also been a shift in chemical toxicity evaluations within the same time frame, with new methodologies being developed to improve chemical safety assessments for both human health and the environment. With increased needs for chemical assessments coupled with more diverse data streams from new technologies, regulators and others tasked with chemical management activities are faced with increasing workloads and more diverse types of data to consider. The Adverse Outcome Pathway (AOP) framework can be applied in different scenarios to integrate data and guide chemical assessment and management activities. In this paper, scenarios of how AOPs can be used to guide chemical management decisions during research and development, chemical registration, and subsequent regulatory activities such as prioritization and risk assessment are considered. Furthermore, specific criteria (e.g., the type and level of AOP complexity, confidence in the AOP, as well as external review and assay validation) are proposed to examine whether AOPs and associated tools are fit for purpose when applied in different contexts. Certain toxicity pathways are recommended as priority areas for AOP research and development, and the continued use of AOPs and defined approaches in regulatory activities are recommended. Furthermore, a call for increased outreach, education, and enhanced use of AOP databases is proposed to increase their utility in chemicals management. Integr Environ Assess Manag 2019;15:633–647. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Nimotuzumab inhibits epithelial–mesenchymal transition in prostate cancer by targeting the Akt/YB‐1/AR axis
Authors: Hu Sheng , Duan Yi‐Xing , Zhou Qiang , Wang Yong , Lu Qiang
Published: March 2019

Nimotuzumab is a humanized anti‐EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3‐AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial–mesenchymal transition (EMT) in vitro and in vivo. The EMT makers were detected by immunohistochemistry, qRT‐PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y‐box binding protein‐1 (YB‐1)/AR axis in nimotuzumab‐induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB‐1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo, which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell‐cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3‐AR cells in vitro. On the molecular level, nimotuzumab inactivated Akt and YB‐1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3‐AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB‐1 activation, and both critical for regulating the levels of AR and EMT‐related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB‐1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1–14, 2019
Undercarboxylated Osteocalcin Improves Insulin-Stimulated Glucose Uptake in Muscles of Corticosterone-Treated Mice
Authors: Lin Xuzhu , Parker Lewan , McLennan Emma , Hayes Alan , McConell Glenn , Brennan-Speranza Tara C , Levinger Itamar
Published: March 2019

Short-term administration of glucocorticoids (GCs) impairs muscle insulin sensitivity at least in part via the reduction of undercarboxylated osteocalcin (ucOC). However, whether ucOC treatment reverses the GC-induced muscle insulin resistance remains unclear. To test the hypothesis that ucOC directly ameliorates impaired insulin-stimulated glucose uptake (ISGU) induced by short-term GC administration in mice muscle and to identify the molecular mechanisms, mice were implanted with placebo or corticosterone (CS) slow-release pellets. Two days post-surgery, insulin-tolerance tests (ITTs) were performed. On day 3, serum was collected and extensor digitorum longus (EDL) and soleus muscles were isolated and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 µU/mL), or both. Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins were assessed. CS administration reduced both serum osteocalcin and ucOC levels, whole-body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment restored ISGU in CS-affected muscle, without increasing non-insulin-stimulated glucose uptake. In CS-affected EDL muscle, ucOC enhanced insulin action on phosphorylated (p-)protein kinase B (Akt)Ser473and the p-extracellular signal-regulated kinase isoform 2 (ERK2)Thr202/Tyr204/total (t)ERK2 ratio, which correlated with ISGU. In CS-affected soleus muscle, ucOC enhanced insulin action on p-mammalian target of rapamycin (mTOR)Ser2481, the p-mTORSer2481/tmTOR ratio, p-Akt substrate of 160kD (AS160)Thr642, and p-protein kinase C (PKC) (pan)Thr410, which correlated with ISGU. Furthermore, p-PKC (pan)Thr410 correlated with p-AktSer473 and p-AS160Thr642. ucOC exerts direct insulin-sensitizing effects on CS-affected mouse muscle, likely through an enhancement in activity of key proteins involved in both insulin and ucOC signaling pathways. Furthermore, these effects are muscle type-dependent. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Circular RNA expression profile in human fibroblast premature senescence after repeated ultraviolet B irradiations revealed by microarray
Authors: Si Chenchen , Wang Jie , Ma Weiwei , Hua Hui , Zhang Meijie , Qian Wen , Zhou Bingrong , Luo Dan
Published: March 2019

Circular RNA (circRNA) is a class of noncoding RNA that regulates the activity of microRNAs and gene expression. Altered circRNA expression is associated with human diseases. The present study profiled differentially expressed circRNAs in the ultraviolet B stress‐induced human fibroblast premature senescence (UVB‐SIPS) model, and assessed the role of circRNA_100797 in UVB‐SIPS. The UVB‐SIPS model was confirmed by ß‐galactosidase staining, cell viability CCK‐8 assay, and flow cytometric cell cycle distribution assay, and subjected to circRNA gene chip profiling. These differentially expressed circRNAs were analyzed using the clusterProfiler R package for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways. The selected circRNAs were confirmed using quantitative reverse transcription polymerase chain reaction (qRT‐PCR), the relationship of circRNA_100797 with miR‐23a‐5p was assessed using luciferase reporter assay, and their functions were determined by qRT‐PCR and western blot analysis. A total of 472 differentially expressed circRNAs occurred in the UVB‐SIPS. qRT‐PCR confirmed five of eight differentially expressed circRNAs. The GO and KEGG analyses revealed that these differently expressed circRNAs function in biology process, cell component, and molecular function. Furthermore, it was found that circRNA_100797 had a low expression in UVB‐SIPS. However, when circRNA_100797 was overexpressed, the acceleration of cell proliferation and alleviation of cell cycle arrest were observed. Moreover, circRNA_100797 could target miR‐23a‐5p, their expression levels were inversely associated in fibroblasts, and the miR‐23a‐5p overexpression blocked the effect of the overexpression of circRNA_100797 in UVB‐SIPS. The present study demonstrated that circRNA_100797 acts as a sponge of miR‐23a‐5p, and has a photoprotection role in UVB‐irradiated fibroblasts.
Inhibition of lncRNA HULC improves hepatic fibrosis and hepatocyte apoptosis by inhibiting the MAPK signaling pathway in rats with nonalcoholic fatty liver disease
Authors: Shen Xingtong , Guo Huaiyuan , Xu Jinjin , Wang Jinliang
Published: March 2019

This study is conducted to investigate the role of long noncoding RNA highly upregulated in liver cancer (lncRNA HULC) on hepatic fibrosis and hepatocyte apoptosis by inhibiting the mitogen‐activated protein kinase (MAPK) signaling pathway in rats with nonalcoholic fatty liver disease (NAFLD). The successfully modeled rats were injected with HULC siRNA or small interfering RNA (siRNA) negative control into the tail vein. The expression of HULC in liver tissues was detected by reverse transcription quantitative polymerase reaction chain. The role of HULC in pathological state and liver function‐related indexes of liver lipid deposition, the degree of hepatic fibrosis and hepatocyte apoptosis in rats with NAFLD were also investigated through a series of experiments. Increased expression of HULC was found in liver tissue of NAFLD rats. Inhibition of HULC improved the pathological state and liver function‐related indexes of liver lipid deposition, improved the degree of hepatic fibrosis, reduced hepatocyte apoptosis, and inhibited the MAPK signaling pathway in the liver tissue of NAFLD rats. The inhibition of p38 and JNK improved the pathological state of liver lipid deposition and liver function to some extent, improved the degree of hepatic fibrosis, and reduced the apoptosis of hepatocytes in NAFLD rats. Collectively, this present study provides evidence that inhibition of lncRNA HULC improves hepatic fibrosis and decrease hepatocyte apoptosis in rats with NAFLD by inhibiting the MAPK signaling pathway.
Epithelial–mesenchymal transition induced cancer‐stem‐cell‐like characteristics in hepatocellular carcinoma
Authors: Jing Li , Ruan Zhiping , Sun Haifeng , Li Qing , Han Lili , Huang Lanxuan , Yu Sizhe , Wang Yu , Guo Hui , Jiao Min
Published: March 2019

Hepatocellular carcinoma in China accounts for half of the world's incidence. Both epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are thought to be involved in tumor malignant progression. However, the relationship between EMT and CSCs is still unclear. Bioinformatics analysis was performed to evaluate the relationship between EMT and CSCs. The EMT and CSC regulatory mechanism was investigated through Transwell, wound‐healing, sphere formation, colony‐forming, and western blotting assays. Immunofluorescence and immunoprecipitation were used to study the interaction of hypoxia inducible factor 1α (HIF‐1α) /Notch1. Immunohistochemical study was applied to investigate the expression pattern in the process of hepatocellular carcinogenesis and development. In our present study, bioinformatics results indicate that the expression of EMT‐related molecules is correlated with CSCs. In vitro studies indicated that EMT activation could induce CSC characteristics. Notch1 was confirmed to mediate the process of EMT‐induced CSCs through the interaction with HIF‐1α directly. Our findings indicate that EMT could induce CSC‐like characteristics, which is mediated by HIF‐1α‐upregulated Notch intracellular domain expression.