bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between schizophrenia and autism spectrum disorder: A systematic review and meta‐analysis
Authors: Zheng Zhen , Zheng Peng , Zou Xiaobing
Published: October 2018

Schizophrenia and autism spectrum disorder (ASD) are significant public health problems. Scientists have recently explored the association between schizophrenia and ASD, but the findings are inconsistent. Thus, we conducted a systematic review and meta‐analysis of epidemiological studies to examine the association between schizophrenia and ASD. PubMed, Embase, and the Cochrane Library were used for literature searches to identify eligible studies published in English before October 2, 2017. Relevant studies estimating the association between schizophrenia and ASD were included. The meta‐analysis of the prevalence of schizophrenia in individuals with ASD encompassed 1,950,113 participants and 14,945 individuals with ASD. A random‐effects model was chosen to synthesize the effect sizes of individual studies. The prevalence of schizophrenia was significantly higher in individuals with ASD than in controls (odds ratio = 3.55, 95% confidence interval: 2.08–6.05, P < .001). Both sensitivity analysis and publication bias testing revealed that the findings were robust. The systematic review of the prevalence of ASD in individuals with schizophrenia encompassed 930 participants. The prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%. The systematic review and meta‐analysis showed a significant association between schizophrenia and ASD. Autism Research 2018, 11: 1110–1119. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

This systematic review and meta‐analysis explored the association between schizophrenia and ASD. We found that the prevalence of schizophrenia was significantly higher in individuals with ASD than in controls and the prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%. A comprehensive estimation of schizophrenia and ASD has important implications for the diagnosis, treatment, prognosis, and development of a fundamental understanding of these disorders.
Bemessung und experimentelle Untersuchungen von eingeschlitzten Verbindungen mit GFK‐Platten und Stabdübeln für den Ingenieurholzbau
Authors: Hartig Jens , Namari Siavash , Wehsener Jörg , Haller Peer
Published: October 2018

Holz ist für den Einsatz in Tragwerken unter korrosiven Bedingungen aufgrund seiner Korrosionbeständigkeit prädestiniert. Häufig stellen dabei jedoch Verbindungen aus Stahl eine Schwachstelle hinsichtlich der Dauerhaftigkeit dar. In diesem Beitrag wird eine Möglichkeit der Ausbildung von Verbindungen aus nichtmetallischen Werkstoffen in Form von glasfaserverstärkten Kunststoffen (GFK) vorgestellt, die im Pultrusionsverfahren hergestellt werden und kommerziell verfügbar sind. Die GFK‐Platten werden dabei in Schlitze im Holzquerschnitt eingebracht und mit Stabdübeln verbunden. Es wird ein Bemessungsmodell auf Grundlage des Eurocodes 5 und der allgemeinen bauaufsichtlichen Zulassung der GFK‐Platten entwickelt und anhand eines Bemessungsbeispiels verdeutlicht. Die Vorhersagen des Bemessungsmodells werden durch Traglastversuche an Trägern mit bauteilnahen Abmessungen überprüft und bestätigt. Es zeigt sich, dass mit den entwickelten Verbindungen ähnliche Trageigenschaften wie mit herkömmlichen eingeschlitzten Stahlverbindungen erreicht werden können. Ein Grund dafür ist das fehlende Lochspiel, das durch ein gleichzeitiges Bohren von Holz‐ und Plattenquerschnitt erreicht wird. Dies erzeugt im Vergleich zu Stahlverbindungen eine gleichmäßigere Belastung der Dübel und geringere Verformungen.
Recent Progress on Transition Metal Oxides as Bifunctional Catalysts for Lithium‐Air and Zinc‐Air Batteries
Authors: Pan Jing , Tian Xin Long , Zaman Shahid , Dong Zehua , Liu Hongfang , Park Ho Seok , Xia Bao Yu
Published: October 2018

In recent years, rechargeable Li‐air and Zn‐air batteries have attracted wide attention due to their high theoretical specific energy densities. However, the high cost and poor stability of noble metal catalysts for the oxygen redox reactions limit their practical large‐scale application. On contrast, low‐cost transition metal oxide (TMO)‐based composite materials exhibit considerable bifunctional activity for oxygen reduction and oxygen evolution, and excellent stability, which holds great potential over the precious metal‐based catalysts. This work briefly introduces the recent advances in TMO‐based composites as bifunctional oxygen electrocatalysts for Li‐air and Zn‐air batteries. After a brief introduction into the research field of air batteries, metal oxides (including Co‐ and Mn‐based oxides) and polymetallic oxides (mainly spinel and perovskite types) are reviewed. In consideration of the poor electronic conductivity of metal oxide catalysts, composites including additional conductive materials are also introduced. Finally, challenges and perspectives of bifunctional TMOs are emphasized to stimulate innovations for the future development of practical Li‐air and Zn‐air batteries.
How can educational research support practice at scale? Attending to educational designer needs
Authors: McKenney Susan , Schunn Christian D.
Published: October 2018

Curricula, assessments and teacher professional development programmes wield a powerful influence on teaching and learning enactment. Together with the interpretation of those using them, these products mediate the flow of ideas from research to practice. In most countries, those curricula, assessments and professional development programmes that become widely used are created by educational designers. Given their crucial function, it is surprising that the role of educational designers is rarely recognised in the educational research literature, studied empirically or supported in practice. This article argues that educational research stands to (better) support practice at scale when it is attuned to the needs of educational designers. First, mechanisms for knowledge production and use are discussed, including the linkage role played by educational designers in the educational infrastructure of most countries. Then, the importance of understanding and bolstering the linkage between research findings and the work of designers is discussed. Arguments are given for research to better support those who design for scale, along with sample research questions posed by educational designers. In these, a distinction is made between the knowledge designers crave to shape their products (curricula, assessments, teacher professional development) and the knowledge they need to shape the processes through which those products come to fruition. This article closes with a call for educational researchers to explicitly focus their knowledge creation and dissemination efforts towards research consumers with the largest direct effects on teaching and learning: educational designers.
Große Stabdurchmesser und hohe Bewehrungsgrade
Authors: Oettel Vincent , Empelmann Martin
Published: October 2018

Durch die Verwendung von großen Stabdurchmessern und hohen Bewehrungsgraden können Stützen mit kleinen Querschnitten hergestellt werden. Diese Stützen besitzen beispielsweise bei der Errichtung von Hochhäusern ein großes ausführungstechnisches und wirtschaftliches Potenzial, da u. a. die Installation der technischen Gebäudeausrüstung vereinfacht und die vermietbare Nutzfläche maximiert werden kann. Der Einsatz solcher Stützen wird allerdings aufgrund fehlender Versuchserfahrungen und durch die vorhandenen normativen Regelungen begrenzt. Um die Herstellbarkeit, Tragfähigkeit und Robustheit solcher hochbewehrten Stützen zu untersuchen, wurden am iBMB, Fachgebiet Massivbau der TU Braunschweig experimentelle und numerische Untersuchungen an normalfesten Stahlbetonstützen mit großen Stabdurchmessern und hohen Bewehrungsgraden durchgeführt. Der vorliegende Beitrag beschreibt die durchgeführten Versuche und stellt die experimentellen und numerischen Ergebnisse vor.
A metabolic control analysis approach to introduce the study of systems in biochemistry: the glycolytic pathway in the red blood cell
Authors: Angelani Carla R. , Carabias Pablo , Cruz Karen M. , Delfino José M. , de Sautu Marilina , Espelt María V. , Ferreira‐Gomes Mariela S. , Gómez Gabriela E. , Mangialavori Irene C. , Manzi Malena , Pignataro María F. , Saffioti Nicolás A. , Salvatierra Fréchou Damiana M. , Santos Javier , Schwarzbaum Pablo J.
Published: October 2018

Metabolic control analysis (MCA) is a promising approach in biochemistry aimed at understanding processes in a quantitative fashion. Here the contribution of enzymes and transporters to the control of a given pathway flux and metabolite concentrations is determined and expressed quantitatively by means of numerical coefficients. Metabolic flux can be influenced by a wide variety of modulators acting on one or more metabolic steps along the pathway. We describe a laboratory exercise to study metabolic regulation of human erythrocytes (RBCs). Within the framework of MCA, students use these cells to determine the sensitivity of the glycolytic flux to two inhibitors (iodoacetic acid: IA, and iodoacetamide: IAA) known to act on the enzyme glyceraldehyde‐3‐phosphate‐dehydrogenase. Glycolytic flux was estimated by determining the concentration of extracellular lactate, the end product of RBC glycolysis. A low‐cost colorimetric assay was implemented, that takes advantage of the straightforward quantification of the absorbance signal from the photographic image of the multi‐well plate taken with a standard digital camera. Students estimate flux response coefficients for each inhibitor by fitting an empirical function to the experimental data, followed by analytical derivation of this function. IA and IAA exhibit qualitatively different patterns, which are thoroughly analyzed in terms of the physicochemical properties influencing their action on the target enzyme. IA causes highest glycolytic flux inhibition at lower concentration than IAA. This work illustrates the feasibility of using the MCA approach to study key variables of a simple metabolic system, in the context of an upper level biochemistry course. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):502–515, 2018.
Resting cells isobutanol production by Shimwellia blattae (p424IbPSO): Influence of growth culture conditions
Authors: Acedos Miguel G. , Santos Victoria E. , Garcia‐Ochoa Felix
Published: October 2018

Isobutanol is a promising gasoline additive and could even be a potential substitute used directly as combustible. In this work, the production of isobutanol from glucose by Shimwellia blattae (p424IbPSO) in resting cell cultures is studied. This production has two stages, involving a resting cell phase that has not been studied before. The cell growth was carried out under different operating conditions: temperature and medium composition (YE, ammonium, and IPTG concentrations), looking for the highest isobutanol production. Moreover, the cells were collected at three different growth times checking their isobutanol production capacity. The best operating conditions have been determined as: 30°C of temperature, a medium containing 1.5 g L−1 YE and 1.4 g L−1of ammonium as nitrogen sources, adding 0.5 mM IPTG as inducer. The cells collected at early growth times are significantly more active. The use of S. blattae (p424IbPSO) in resting cells is a good strategy for the production of isobutanol from glucose yielding better results than in batch growth cultures, a yield of 60% attainment of theoretical maximum yield is obtained under optimal conditions. In addition, it has been demonstrated that if the cells are cultured at higher temperatures and with high IPTG concentrations, inclusion bodies are formed in the cytoplasm inhibiting the isobutanol production in the resting cell stage.
Establishment of a CFD‐based kLa model in microtiter plates to support CHO cell culture scale‐up during clone selection
Authors: Wutz Johannes , Steiner Robin , Assfalg Kerstin , Wucherpfennig Thomas
Published: October 2018

Microtiter plates are a common tool for clone selection in biopharmaceutical development. A way of visualizing and evaluating these systems and key processes parameters is the application of Computational Fluid Dynamics (CFD). CFD is a powerful tool for the modelling of hydrodynamics and mass transfer parameters. In this work, CFD was used to determine the specific surface area, the volumetric power input and the oxygen mass transfer coefficient kLa for two different microtiter plates with different scales (100 μL ‐ 5 mL). For this purpose, a new method of predicting the kLa is presented and calibrated with literature data. Scaling effects in shaken microtiter plates are evaluated by comparing two culture volume scales under various operating conditions. To test validity of these models, three different Boehringer Ingelheim Pharma proprietary CHO production cell lines with different growth characteristics were cultivated using the respective microtiter plates under different conditions until limitations in growth and viability were observable. The cell culture data then was compared to different parameters obtained by CFD. The calculated kLa values match the cell culture performance in the 96‐deepwell by predicting lowered oxygen transfer with increasing culture volume and decreasing orbital velocity. The same cells behave differently in the 6‐deepwell scale. Here, the overall larger shear stress might cause physical stress for the cells. The kLa model predicts overall higher shear rates for this system, supporting the experimental findings. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018
The effect of feed quality due to clarification strategy on the design and performance of protein A periodic counter‐current chromatography
Authors: El‐Sabbahy Hani , Ward David , Ogonah Olotu , Deakin Lynne , Jellum Gregory M. , Bracewell Daniel G.
Published: October 2018

The impact of two different quality feeds, derived using two different harvest clarification processes, on protein A periodic counter‐current chromatography (PCC) design and performance is investigated. Data from batch experiments were input into a model to design optimal PCC operating parameters specific to each feed material. The two clarification methods were: depth filtration using a wetlaid matrix which has Q‐functionality; and a combination of depth filtration and chromatographic clarification, using a Q‐functional nonwoven with a high anion exchange capacity (Emphaze™ AEX Hybrid Purifier) in which key impurities such as host cell DNA (HCDNA) and host cell proteins (HCP) are removed. The model predicted 34% better productivity for the chromatographically clarified cell culture fluid (CCCF) using a 4 column system, and productivity gains of 28% using only 3 columns enabling the option to simplify the protein A PCC strategy. Experimental validation of the predicted optimized PCC operating parameters using industrially relevant monoclonal antibody (mAb) CCCF feedstock over 100 cycles showed productivity gains of 49% for the chromatographically clarified material. HCP concentration was 11‐fold lower, and HCDNA concentration was reduced by 4.4 Log Reduction Value (LRV) in the protein A PCC eluates. This work, therefore, demonstrates that the removal of HCDNA and HCP during clarification is an effective strategy for improving protein A PCC performance. This was achieved using the Emphaze™ AEX Hybrid Purifier which can be easily incorporated into a batch or continuous process, in a scalable fashion, without adding additional separate unit operations. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1380–1392, 2018
Cell pretreatment with ethylenediaminetetraacetic acid for selective extraction of C‐phycocyanin with food grade purity
Authors: Sala Luisa , Moraes Caroline Costa , Kalil Susana Juliano
Published: October 2018

C‐phycocyanin (C‐PC) is a natural blue dye, and depending on its purity, which is measured by the ratio between the absorbance of the chromophore (A620) and the absorbance of the proteins (A280), it can be used in food (purity > 0.7), cosmetics (purity > 1.5), and therapeutic treatments (purity > 4.0). Several physical, chemical, and enzymatic methods of extraction are reported, however, few are able to extract C‐PC with purity above 0.7. An innovative method of C‐PC extraction with food grade purity from wet Spirulina platensis biomass is proposed. The cells were pretreated with ethylenediaminetetraacetic acid and subsequent C‐PC extraction was performed with tris‐(hydroxymethyl) aminomethane‐SO4 buffer. C‐PC was released after 12 h of cell pretreatment. Six variables of the extraction process were evaluated. The extraction temperature significantly influenced C‐PC extraction yield and purity. In the best condition of cell pretreatment and extraction, C‐PC with purity of 1.0 and extraction yield of 129.0 mg/g could be obtained to be used as a food dye without any purification process. Lastly, an ultrafiltration process was integrated and C‐PC was concentrated 8.8‐fold, resulting in purity of 1.6 and recovery of 93.4%.
Lipase‐catalyzed hydrolysis of (R,S)‐2,3‐diphenylpropionic methyl ester enhanced by hydroxypropyl‐β‐cyclodextrin
Authors: Cheng Qing , Liu Guangyong , Zhang Panliang , Xu Weifeng , Tang Kewen
Published: October 2018

The enantioselective hydrolysis of (R,S)‐2,3‐diphenylpropionic methyl ester ((R,S)‐2,3‐2‐PPAME) catalyzed by lipase to (R)‐2,3‐diphenylpropionic acid ((R)‐2,3‐2‐PPA) was studied in an aqueous system. The catalytic effects of different types of lipase were compared, and Candida antarctica lipase A (CALA) with higher catalytic activity and enantioselectivity was selected. Hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was added to the aqueous system to increase the solubility of 2,3‐2‐PPAME, which resulted in an increase of 35.56% in substrate conversion remaining the high enantiomeric excess. The factors influencing the substrate conversion and the optical purity of product such as temperature, pH, concentrations of CALA and HP‐β‐CD, substrate loading, and reaction time were optimized. The optimal conditions for this reaction were obtained, including pH of 5.5, 30 mg/mL CALA, 25 mmol/L HP‐β‐CD, 0.12 mmol substrate, temperature at 60 °C, agitation speed at 400 rpm, and 48 h for reaction time. Under these optimal conditions, the substrate conversion was up to 44.70% and the optical purity of the product (R)‐2,3‐2‐PPA was up to 98.20%. This work provides an efficient alternative method for lipase‐catalyzed enantioselective hydrolysis of 2,3‐2‐PPAME to (R)‐2,3‐2‐PPA by β‐cyclodextrin inclusion in an aqueous reaction system of hydrolysis. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1355–1362, 2018
The transplantation of corneae from cadavers can prevent blindness
Authors: Tschernig Thomas , Seitz Berthold
Published: October 2018

This Viewpoint describes the process by which corneae are obtained from body donors to anatomical institutes for subsequent clinical transplantation. Corneae from body donors are extremely valuable in clinical medicine. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.
Preservation of neural tissue with a formaldehyde‐free phenol‐based embalming protocol
Authors: Tomalty Diane , Pang Stephen C. , Ellis Randy E.
Published: October 2018

The adverse effects formaldehyde fixation has on tissues both gross anatomically and histologically are well documented. Consequently, researchers are seeking alternative embalming techniques that better preserve in vivo characteristics of tissues. Phenol‐based embalming is one method that has shown promise in its ability to adequately preserve the in vivo qualities of tissues through preliminary explorations at the gross anatomical level. The literature on phenol‐based embalming is currently scarce, especially with regard to its effects on tissues at the microscopic level. For the current study we aimed to document the histologic effects of a formaldehyde‐free phenol‐based embalming solution on neural tissue, with the hope of providing novel insight into the effects of soft‐embalming on tissues at the microscopic level. Cerebral and cerebellar tissue obtained from porcine brains was fixed in phenol‐ and formaldehyde‐based fixatives; the latter served as a control. Fixed samples were processed for histological analysis. The phenol‐based embalming solution provided excellent preservation of the cerebral and cerebellar tissue morphology. Of note was the decrease in separation artifact seen in both tissue types relative to the control tissue, as well as anomalous circular artifacts in the white matter. The results of this study indicate that the phenol‐based embalming solution preserves neural tissue at the histological level, perhaps superiorly in many aspects when compared to the formaldehyde‐fixed samples. Further investigations of both gross anatomy and histology are recommended on the basis of these promising new findings to determine its potential utilities within research and education. Clin. Anat. 32:224–230, 2019. © 2018 Wiley Periodicals, Inc.
It takes time to tango: The relative importance of values versus traits in consumer brand relationships
Authors: Voorn Ronald J.J. , van der Veen Gerrita , van Rompay Thomas J.L. , Pruyn Ad T.H.
Published: October 2018

Brand managers have several options in their quest to connect their brands with consumers. They may stress functional brand attributes and benefits, their brand's personality traits, or their brand's values (the human values attached to the brand). Which of these is most important to consumers is an open question, however. This article proposes that values may take on increased importance over time, as long‐term relationships (in general) require more than just getting the job done (functional aspect) or a sense of recognition (trait correspondence). What is required most of all is a correspondence between long‐term objectives and goals in life. Values are arguably the most relevant factor in longer relationships. An experiment was put together to determine if this is indeed the case. The results of our study suggest that values are indeed considered more important than traits in the case of longer relationships and that this is particularly true with decisions regarding prospective relationships and in the case of services.
The Coordination Chemistry of Copper Uptake and Storage for Methane Oxidation
Authors: Dennison Christopher
Published: October 2018

Methanotrophs are remarkable bacteria that utilise large quantities of copper (Cu) to oxidize the potent greenhouse gas methane. To assist in providing the Cu they require for this process some methanotrophs can secrete the Cu‐sequestering modified peptide methanobactin. These small molecules bind CuI with very high affinity and crystal structures have given insight into why this is the case, and also how the metal ion may be released within the cell. A much greater proportion of methanotrophs, genomes of which have been sequenced, possess a member of a newly discovered bacterial family of copper storage proteins (the Csps). These are tetramers of four‐helix bundles whose cores are lined with Cys residues enabling the binding of large numbers of CuI ions. In methanotrophs, a Csp exported from the cytosol stores CuI for the active site of the ubiquitous enzyme that catalyses the oxidation of methane. The presence of cytosolic Csps, not only in methanotrophs but in a wide range of bacteria, challenges the dogma that these organisms have no requirement for Cu in this location. The properties of the Csps, with an emphasis on CuI binding and the structures of the sites formed, are the primary focus of this review.
One Step up the Ladder of Prebiotic Complexity: Formation of Nonrandom Linear Polypeptides from Binary Systems of Amino Acids on Silica
Authors: Sakhno Yuriy , Battistella Alice , Mezzetti Alberto , Jaber Maguy , Georgelin Thomas , Michot Laurent , Lambert Jean‐François
Published: October 2018

Evidence for the formation of linear oligopeptides with nonrandom sequences from mixtures of amino acids coadsorbed on silica and submitted to a simple thermal activation is presented. The amino acid couples (glutamic acid+leucine) and (aspartic acid+valine) were deposited on a fumed silica and submitted to a single heating step at moderate temperature. The evolution of the systems was characterized by X‐ray diffraction, infrared spectroscopy, thermosgravimetric analysis, HPLC, and electrospray ionization mass spectrometry (ESI‐MS). Evidence for the formation of amide bonds was found in all systems studied. While the products of single amino acids activation on silica could be considered as evolutionary dead ends, (glutamic acid+leucine) and, at to some extent, (aspartic acid+valine) gave rise to the high yield formation of linear peptides up to the hexamers. Oligopeptides of such length have not been observed before in surface polymerization scenarios (unless the amino acids had been deposited by chemical vapor deposition, which is not realistic in a prebiotic environment). Furthermore, not all possible amino acid sequences were present in the activation products, which is indicative of polymerization selectivity. These results are promising for origins of life studies because they suggest the emergence of nonrandom biopolymers in a simple prebiotic scenario.
A Nano‐Sized [MnII18] Metallamacrocycle as a Building Unit to Construct Stable Metal–Organic Frameworks: Effective Gas Adsorption and Magnetic Properties
Authors: Zhou Lei , Zhou Baolei , Cao Shanshan , Cui Zheng , Qin Bowen , Li Wenliang , Zhang Xiaoying , Zhang Jingping
Published: October 2018

A stable hex‐type metal‐organic framework (MOF, WMOF‐1) was constructed by nano‐sized [MnII18] metallamacrocycle secondary building unit, being the one with the highest nuclearity of manganese wheel‐like node in the microporous MOF. WMOF‐1 displays an effective gas adsorption and the antiferromagnetic behavior.
Comparison of adiposity indices in relation to prehypertension by age and gender: A community‐based survey in Henan, China
Authors: Wang Shuaibing , Peng Rui , Liang Shuying , Dong Kaiyan , Nie Wei , Yang Qian , Ma Nan , Zhang Jianying , Wang Kaijuan , Song Chunhua
Published: October 2018

Background

To compare the efficiency of bioelectrical indices (visceral fat index [VFI], percentage body fat [PBF]) and anthropometric indices (body mass index, waist circumference, waist‐to‐height ratio, a body shape index ) in the relation to prehypertension (120‐139/80‐89 mm Hg) among the Chinese population.

Methods

Using stratified multistage random sampling method, a general population‐based sample of 11 175 adults in Henan province were selected from 2013 to 2015. The individuals were divided into three categories by blood pressure levels: normotension (<120 and 80 mm Hg), stage 1 prehypertension (120‐129/80‐84 mm Hg) and stage 2 prehypertension (130‐139/85‐89 mm Hg).

Results

VFI and PBF tended to increase with age in men and women. However, for each age‐specific group, men tended to have higher VFI than women (all P < 0.01) and women tended to have greater PBF (all P < 0.0001). The odds ratios (OR) and area under the receiver operating characteristic curves for prehypertension associated with adiposity indices declined with age. VFI and PBF showed higher standardized adjusted ORs for prehypertension in young (~40 years) men (VFI: 2.02‐3.05; PBF: 1.82‐2.80) and young women (VFI: 1.90‐2.58; PBF:1.70‐2.29). Moreover, based on Youden's index, VFI and PBF exhibited the superiority for identifying prehypertension in men (0.20‐0.32) and women (0.31‐0.39), respectively.

Conclusion

In summary, there was stronger association of VFI and PBF with prehypertension in men than in women, respectively, especially for young adults.
Guideline‐directed statin intensification in patients with new or worsening symptoms of peripheral artery disease
Authors: Khariton Yevgeniy , Patel Krishna K. , Chan Paul S. , Pokharel Yashashwi , Wang Jingyan , Spertus John A. , Safley David M. , Hiatt William R. , Smolderen Kim G.
Published: October 2018

Background

The ACC/AHA cholesterol guidelines recommend patients with peripheral artery disease (PAD) be treated with a moderate to high‐intensity statin. The extent to which patients with new or worsening PAD symptoms are offered guideline therapy is unknown.

Hypothesis

There is significant variability in rate of guideline‐directed statin intensification across clinical practices.

Methods

In the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients at 16 PAD specialty clinics between June 2011 and December 2015 before and after an evaluation for new or worsening claudication symptoms. We documented whether patients were treated with a guideline statin as well as the incidence of statin intensification. Statin intensification was defined as transitioning from no statin or low‐intensity statin to moderate or high‐intensity statin treatment. Patient factors associated with intensification were examined. Site and provider‐level variation in intensification was summarized using an adjusted median odds ratio (aMOR).

Results

Among 1144 patients, 810 (70.8%) were initially on guideline therapy compared to 334 (29.2%) that were not. In the latter, 103 (30.8%) received intensification following evaluation. Patients with typical symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23‐11.41) while older patients had lower odds of intensification (OR 0.60/decade; 95% CI: 0.41‐0.88). Site variability for statin intensification was observed across sites (aMOR = 3.15; 95% CI 1.22‐9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95% CI 1.00‐3.90, [P = 0.14]).

Conclusions

Most patients evaluated at a PAD specialty clinic for new or worsening claudication symptoms arrived on guideline statin therapy. Only 31% not receiving appropriate therapy underwent statin intensification. These findings highlight an important opportunity to optimize medical therapy for patients with PAD.
Impact of atrial fibrillation on patients hospitalized for acute myocarditis: Insights from a nationally‐representative United States cohort
Authors: Subahi Ahmed , Akintoye Emmanuel , Yassin Ahmed S. , Abubakar Hossam , Adegbala Oluwole , Mishra Tushar , Abdelrahman Mohamed , Shokr Mohamed , Afonso Luis
Published: October 2018

Background

Atrial fibrillation (AF) is associated with increased all‐cause mortality in the general population. However, the impact of AF on the in‐hospital outcomes of acute myocarditis (AM) patients is not well characterized.

Methods

Patients (age ≥ 18 years) with a primary diagnosis of AM in the National Inpatient Sample from 2007 to 2014 were included, using the ICD‐9‐CM diagnostic codes. We compared the in‐hospital outcomes between the AF group and propensity score‐matched control group without AF.

Results

AF was reported in 602 (9%) of the AM patients. Compared to those without AF, AM patients with AF experienced higher in‐hospital mortality (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1‐2.7, P = 0.02). AF was associated with higher risk of cardiogenic shock (OR 1.9, 95% CI 1.3‐2.8, P < 0.001), cardiac tamponade (OR 5.6, 95% CI 1.2‐25.3, P = 0.002) and acute kidney injury (OR 1.6, 95% CI 1.1‐2.1, P = 0.02). Furthermore, patients with AF were more likely to have non‐routine hospital discharge (31.6% vs 38.4% P = 0.02), longer length of stay and higher cost of hospitalization.

Conclusions

AF was associated with increased risk of in‐hospital mortality and complications in patients admitted to the hospital with acute myocarditis.
Organization of the catecholaminergic systems in two basal actinopterygian fishes, Polypterus senegalus and Erpetoichthys calabaricus (Actinopterygii: Cladistia)
Authors: López Jesús M. , Lozano Daniel , Morona Ruth , González Agustín
Published: October 2018

Cladistians are a group of basal nonteleost actinopterygian fishes that represent an interesting group for the study of primitive brain features, most likely present in the ancestral Osteichthyes. We have investigated the catecholaminergic (CA) systems in the brain of two representative cladistian species, the bichir Polypterus senegalus and the reedfish Erpetoichthys calabaricus, by means of antibodies against tyrosine hydroxylase (TH; the first enzyme in the synthesis of catecholamines) and dopamine (DA). Double immunohistofluorescence was performed for simultaneous detection of TH with nitric oxide synthase, choline acetyltransferase, calbindin, calretinin, and serotonin, aiming to accurately establish the localization of the CA neurons and to assess possible interactions between these neuroactive substances. All forebrain CA groups of cladistians are dopaminergic, whereas noradrenergic cells are located within the rhombencephalon. Distinct groups of DA immunoreactive (DA‐ir) cells were observed in the olfactory bulb, subpallium, and preoptic area of the telencephalon. Hypothalamic groups were detected in the suprachiasmatic nucleus, retrotuberal and retromamillary areas and, in particular, the paraventricular organ showed immunoreactivity to dopamine but not to TH. Diencephalic DA‐ir groups were detected in the prethalamus, posterior tubercle, and pretectum. A small DA‐ir cell population was observed in the midbrain tegmentum only in Polypterus. CA cell groups were also located in the locus coeruleus, solitary tract nucleus, and area postrema within the rhombencephalon, the spinal cord, and the retina. The comparison of these results with other vertebrates, using a neuromeric analysis, shows highly conserved traits in all vertebrates studied but also evidences particular characteristics of actinopterygian fishes.
Preference and harmony of neutral colours in 50‐year apart
Authors: Nemcsics Antal , Takacs Jeno
Published: October 2018

Within the framework of this article the results of two experiments are compared, on the preference and harmony content of neutral colours, carried out 50‐year apart, in 1967 and 2017. The experimental conditions and sample boards, shown to the experimental subjects were identical in both occasions. Result shows that in 2017 the very light and very dark colours have been preferred over other colours, against the findings in1967. At the same time, the experimental subjects found the colour pairs, formed of colours with higher contrast, more harmonic in 2017 than 50‐year earlier in 1967.
Propagation and Purification of Ectromelia Virus
Authors: Chaudhri Geeta , Kaladimou Georgina , Pandey Pratikshya , Karupiah Gunasegaran
Published: October 2018

Ectromelia virus (ECTV) is an orthopoxvirus that causes mousepox in mice. Members of the genus orthopoxvirus are closely related and include variola (the causative agent of smallpox in humans), monkeypox, and vaccinia. Common features of variola virus and ECTV further include a restricted host range and similar disease progression in their respective hosts. Mousepox makes an excellent small animal model for smallpox to investigate pathogenesis, vaccine and antiviral agent testing, host‐virus interactions, and immune and inflammatory responses. The availability of a wide variety of inbred, congenic, and gene‐knockout mice allows detailed analyses of the host response. ECTV mutant viruses lacking one or more genes encoding immunomodulatory proteins are being used in numerous studies in conjunction with wild‐type or gene‐knockout mice to study the functions of these genes in host‐virus interactions. The methods used for propagation of ECTV in cell culture, purification, and quantification of infectious particles through viral plaque assay are described. © 2018 by John Wiley & Sons, Inc.
Ni‐Catalyzed α‐Alkylation of Unactivated Amides and Esters with Alcohols by Hydrogen Auto‐Transfer Strategy
Authors: Midya Siba P. , Rana Jagannath , Pitchaimani Jayaraman , Nandakumar Avanashiappan , Madhu Vedichi , Balaraman Ekambaram
Published: October 2018

A transition‐metal‐catalyzed borrowing hydrogen/hydrogen auto‐transfer strategy allows the utilization of feedstock alcohols as an alkylating partner, which avoids the formation of stoichiometric salt waste and enables a direct and benign approach for the construction of C‐N and C−C bonds. In this study, a nickel‐catalyzed α‐alkylation of unactivated amides and ester (tert‐butyl acetate) is carried out by using primary alcohols under mild conditions. This C−C bond‐forming reaction is catalyzed by a new, molecularly defined nickel(II) NNN‐pincer complex (0.1–1 mol %) and proceeds through hydrogen auto‐transfer, thereby releasing water as the sole byproduct. In addition, N‐alkylation of cyclic amides under Ni‐catalytic conditions is demonstrated.
Compromising Between Phase Stability and Electrical Performance: SrVO3–SrTiO3 Solid Solutions as Solid Oxide Fuel Cell Anode Components
Authors: Macías Javier , Yaremchenko Aleksey A. , Rodríguez‐Castellón Enrique , Starykevich Maksim , Frade Jorge R.
Published: October 2018

The applicability of perovskite‐type SrVO3−δ in high‐temperature electrochemical energy conversion technology is hampered by the limited stability domain of the perovskite phase. The aim of the present work was to find a compromise between the phase stability and electrical performance by designing solid solutions in the SrVO3–SrTiO3 system. Increasing titanium content in SrV1−yTiyO3−δ (y=0–0.9) perovskites is demonstrated to result in a gradual shift of the upper‐p(O2) phase stability boundary toward oxidizing conditions: from ≈10−15 bar at 900 °C for undoped SrVO3−δ to ≈10−11–10−5 bar for y=0.3–0.5. Although the improvement in the phase stability is accompanied by a decrease in electrical conductivity, the conductivities of SrV0.7Ti0.3O3−δ and SrV0.5Ti0.5O3−δ at 900 °C remain as high as 80 and 20 S cm−1, respectively, and is essentially independent of p(O2) within the phase‐stability domain. Combined XRD, thermogravimetric analysis, and electrical studies revealed very sluggish kinetics of oxidation of SrV0.5Ti0.5O3−δ ceramics under inert gas conditions and a nearly reversible behavior after exposure to an inert atmosphere at elevated temperatures. Substitution by titanium in the SrV1−yTiyO3−δ system results also in a decrease of oxygen deficiency in perovskite lattice and a favorable suppression of thermochemical expansion. Variations of oxygen nonstoichiometry and electrical properties in the SrV1−yTiyO3−δ series are discussed in combination with the simulated defect chemistry of solid solutions.
A new code‐based designated verifier signature scheme
Authors: Thanalakshmi Perumal , Anitha Ramalingam
Published: October 2018

Designated verifier signature (DVS) scheme allows the verifier to verify the signature of a message but prevents from transferring the conviction to any third party. This scheme is useful in circumstances where authenticity, signer ambiguity, and signer's privacy are simultaneously needed in various applications such as electronic voting, call for tenders, etc. Most of the existing DVS schemes are based on the hard problems in number theory such as integer factorization or the discrete log problem. The construction of a large‐scale quantum computer would break those schemes. So, the National Institute of Standards and Technology Internal Report recommends to develop cryptographic systems that are secure against both the quantum and the classical computers. One such promising alternative to number theoretic cryptography is code‐based cryptography. This paper analyzes the code‐based strong designated verifier schemes proposed in 2016 by Ren et al and Koochak Shooshtari et al and shows that these schemes do not have non‐transferability which is the essential feature of a DVS scheme. Further, the paper proposed a DVS scheme built on syndrome decoding, a hard problem in coding theory, and proves its security properties such as unforgeability and non‐transferability in the random oracle model.
Fine needle aspiration biopsy cytology of phyllodes tumour and fibroadenoma: A cytomorphological study of 104 cases
Authors: Wang Xue Yu , Mahajan Hema , Dickinson Nicole , Cox Carol , Byth Karen , Bayly Angela , Cahill Michael A. , Pathmanathan Nirmala
Published: October 2018

Background

The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT.

Methods

FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78) cases were retrieved from a retrospective database interrogation from the Department of Cytology/Tissue Pathology, ICPMR Pathology West (Cerner Millennium) in Westmead Hospital. For each case, two smears were selected, de‐identified and independently reviewed by four observers comprising two cytologists and two cytopathologists. Cytological parameters examined included detailed evaluation of smear cellularity, epithelial and stromal components as well as the smear background.

Results

The cytological features of moderate to marked stromal cellularity and stromal nuclear atypia were more evident in PT than in FA, identified by three out of four observers. The epithelial characteristics, presence of macrophages, multinucleated giant cells and blood vessels showed no statistically significant differences in the distinction between the two lesions.

Conclusion

The results of this study indicate that in all of the cytological features assessed for PT and FA, no single cytological feature was found to be statistically significant in identifying PT across all observers. This reflects the overlap of cytological features seen in these lesions. FNAB cytology cannot reliably distinguish FA and PT.
Effects of using lubricant during the speculum examination for Pap smear collection
Authors: Nunes Rodrigo Dias , Cascaes Maisa , Schneider Ione Jayce Ceola , Traebert Jefferson
Published: October 2018

Objective

To evaluate the effect of using lubricant during speculum examination for Pap smear collection.

Methods

A cross‐sectional study was conducted involving 83 patients attending a medical school clinic. Participants were allocated into two groups: Group 1—Lubricant using; Group 2—No lubricant using. All patients were submitted to two successive collections and after were asked about their level of discomfort. Differences between groups regarding quality, artifacts, cytology, and level of discomfort were observed through chi‐squared test. Odds ratios and 95% confidence intervals were also estimated. Statistical significance was set at P < .05.

Results

No significant differences between groups regarding quality, presence of artifacts, and cytological results were observed. Significant lower discomfort level in Group 1 (lubricant using).

Conclusion

The use of vaginal lubricant did not affect the results of cytology and could be a useful tool to reduce the discomfort during Pap smear collection.
Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the lung and pancreas
Authors: Yoxtheimer Lorene M. , Heymann Jonas J. , Cohen Cynthia , Rao Rema A. , Goyal Abha , Siddiqui Momin T.
Published: October 2018

Background

Homeobox transcription factors have demonstrated utility in diagnosing neuroendocrine tumors. Orthopedia homeobox protein (OTP) has a well‐defined role in embryonic neurodevelopment and has also been described as a prognostic marker in lung neuroendocrine tumors (NET). Additionally, NK6 homeobox‐1 (NKX6.1) has been described to be necessary for the development of neuroendocrine cells in the pancreas. We evaluated immunohistochemical (IHC) expression of OTP and NKX6.1 to determine their utility in the diagnosis of NETs from lung and pancreas fine‐needle aspirations (FNA).

Methods

Our study examined 50 FNA specimens, including 30 primary pulmonary NETs (8 carcinoid tumors (CT), 6 atypical carcinoids (AC), 11 small‐cell neuroendocrine carcinomas (SCNEC), 5 large‐cell neuroendocrine carcinomas (LCNEC)) and 20 primary pancreatic NETs (17 well‐differentiated pancreatic neuroendocrine tumors (PanNET) and 3 poorly differentiated pancreatic neuroendocrine carcinomas (PanNEC)). IHC expression of OTP, NKX6.1, and Ki‐67 was evaluated on FNA cell blocks.

Results

Half of the pulmonary TC tumors expressed OTP, while only 17% of AC and 20% of LCNEC expressed OTP. Neither SCNECs nor any pancreatic NET expressed OTP. In contrast, intermediate and high‐grade tumors expressed NKX6.1 (LCNEC‐80%, SCNEC‐82%, and AC‐83%) more often than low‐grade tumors (TC‐63%, PanNET‐71%). All three PanNECs expressed NKX6.1.

Conclusions

OTP may be useful in diagnosing well‐differentiated NETs of pulmonary origin. NKX6.1 may have utility in segregating high from low‐grade NETs of both pulmonary and pancreatic origin, although other methods will be required to determine site of origin.
Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone
Authors: Singh Sandeep K. , Valicherla Guru R. , Joshi Pankaj , Shahi Sudhir , Syed Anees A. , Gupta Anand P. , Hossain Zakir , Italiya Kishan , Makadia Vishal , Singh Shio K. , Wahajuddin Mohammad , Gayen Jiaur R.
Published: October 2018

Preclinical Research & Development

Withanolide A (WA), a steroidal lactone is a major bioactive constituent of Withania somnifera (L.) with remarkable neuropharmacological activity. In this study, we investigated the permeability, plasma protein binding (PPB), blood partitioning, intravenous (i.v.), and oral pharmacokinetics as well as i.v. tissue distribution (TD) of pure WA in a rat model. The PPB, RBCs partitioning, and permeability of WA were determined by Ultra Performance Liquid Chromatography (UPLC) method. However, the pharmacokinetics and TD of WA were evaluated by validated and sensitive liquid chromatography coupled mass spectrometry (LC‐ESI‐MS/MS) method. The PPB and permeability of WA were determined by equilibrium dialysis and parallel artificial membrane permeability assay method, respectively. The results demonstrated that WA has high PPB and passive permeability. Furthermore, WA was found to have fast equilibration between RBCs and plasma. Following i.v. (2 mg/kg) and per‐oral (25 mg/kg) administration of WA, the max concentration (Cmax) in plasma was found as 85.53 ± 6.54 and 48.04 ±5.78 ng/mL, respectively. The TD study results indicated that WA has a rapid and wide TD. The maximum concentration in various tissues was found in following order: Clung > Cliver > Ckidney ≈ Cspleen > Cheart > Cbrain. The preclinical in vitro, as well as pharmacokinetics and TD results, are anticipated to support the future preclinical and clinical application of WA.
High‐throughput doping control analysis of 28 amphetamine‐type stimulants in equine plasma using hydrophilic interaction liquid chromatography–tandem mass spectrometry
Authors: You Youwen , Guan Fuyu , D'Ippolito Robert , Li Xiaoqing , Soma Lawrence R. , Robinson Mary A.
Published: October 2018

A hydrophilic interaction liquid chromatography–tandem mass spectrometry method (HILIC–MS/MS) was developed for the simultaneous determination of 28 amphetamine‐type stimulants (ATSs) in equine plasma for doping control analysis. In this method, stimulants were recovered from equine plasma by liquid–liquid extraction (LLE) at pH 9.5 using methyl tert‐butyl ether and detected on a Thermo Finnigan triple quadrupole mass spectrometer operating in positive‐ion mode electrospray ionization. All stimulants were eluted within 7 minutes and baseline separation was achieved for isomeric and isobaric compounds using HILIC chromatography. Extraction efficiency was greater than 80% and matrix effect was acceptable for most stimulants. The limit of detection (LOD) was in the range of 10–50 pg/mL and the lower limit of quantification (LLOQ) was in the range of 50–100 pg/mL. Quadratic regression was employed for quantification and the dynamic range of quantification was 50–10000 pg/mL. Confirmatory analysis criteria were established using product ion ratios and retention time. The limit of confirmation (LOC) was in the range of 20–100 pg/mL. Stability study results indicated that some stimulants were unstable in equine plasma at room temperature and 4°C. However, all the stimulants studied were stable at −20°C and − 80°C for the 6 month study period.