bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of β1 blockade with atenolol on progression of heart failure in patients pretreated with high‐dose enalapril
Authors: Sturm Barbara , Pacher Richard , Strametz‐Juranek Jeanette , Berger Rudolf , Frey Bernhard , Stanek Brigitte
Published: July 2002

Background

The survival benefit of β‐blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of β‐blockers added on high dose angiotensin converting enzyme inhibitors has not been reported.

Aims

To investigate the effect of atenolol, a hydrophilic, selective β1‐adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double‐blind placebo‐controlled trial.

Methods

One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction ≤25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12.5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89±11 mg/day, range 50–100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events.

Results

After 395±266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty‐seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo‐group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01)

Conclusions

The data suggest that in patients with advanced left ventricular dysfunction, β‐blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.
Dantrolene sodium improves the force–frequency relationship and β‐adrenergic responsiveness in failing human myocardium
Authors: Meissner Achim , Min Jiang‐Yong , Haake Nils , Hirt Stephan , Simon Rüdiger
Published: July 2002

Background:

Failing human myocardium is characterized by a negative force–frequency relationship and impaired β‐adrenergic responsiveness which have been related to alterations of the intracellular Ca2 homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial Ca2 i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2 handling and contractile function in failing human myocardium.

Methods and Results:

Twenty‐three muscle strips from human left ventricular trabeculae were obtained from patients undergoing heart transplantation for end‐stage heart failure caused by idiopathic dilated cardiomyopathy (n=15). Isometric contraction and intracellular Ca2 transients (Ca2 indicator: aequorin) were recorded simultaneously. The experiments were performed in three separate groups exposed to control condition (n=8), addition of dantrolene (10 μmol/l; n=8), or addition of verapamil (1 μmol/l; n=7). Isoproterenol induced a moderate positive inotropic effect in the control group with a maximal increase of developed tension from 10.8±2.9 to 23.4±4.7 mN/mm2 and a parallel rise in peak systolic Ca2 i to a maximum of 1.36±0.20 μmol/l. Dantrolene significantly improved (10.2±3.8 to 32.4±0.9 mN/mm2) and verapamil blunted (8.3±2.8 to 17.1±4.3 mN/mm2) the inotropic response to isoproterenol. The diastolic and systolic Ca2 i during isoproterenol stimulation were slightly lower in the dantrolene group but significantly depressed in the verapamil group as compared to the control group. Similarly, analyses of force–frequency relationships revealed an improvement of developed tension in dantrolene‐treated as compared to control preparations whereas the peak systolic Ca2 i was almost identical.

Conclusion:

Dantrolene improves the negative force–frequency relationship and β‐adrenergic responsiveness in failing human myocardium. These effects are not accompanied by an additional increase in intracellular Ca2 i but might be related to modifications of the diastolic Ca2 i homeostasis.
Microarray‐based transcriptional profiling of a mouse model of autoimmune hepatitis
Authors: Liu Yang , Chen Hao , Hao Jian‐heng , Li Zhen‐cheng , Hou Tiezheng , Hao Hui‐qin
Published: August 2020

Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not typically code for a protein. lncRNAs have regulatory roles in many physiological processes, and their dysregulation can contribute to cancer, cardiovascular and neurodegenerative diseases, as well as the onset of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. However, lncRNA expression changes in autoimmune hepatitis (AIH), a form of inflammation induced by immunological tolerance disorders, are poorly understood. Here, for the first time to our knowledge, we used microarrays to profile 1161 differentially expressed lncRNAs (DELs; 608 up‐ and 553 down‐regulated) and 11 512 differentially expressed mRNAs (DEMs; 5189 up‐ and 6323 down‐ regulated) in a concanavalin A‐induced AIH mouse model. We used quantitative real‐time PCR to confirm the expression of eight DELs and DEMs, and analyzed the coexpression relationship between them. Potential biological functions of screened DELs and DEMs were predicted with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. DEL‐DEM interaction networks were also constructed. Our study revealed the roles of DELs and DEMs in the pathogenesis of AIH. We also provided potential candidate biomarkers that may have potential for future development into possible diagnostics or as a treatment for this disorder.
The role of empathy and social anxiety in Latinx adolescents' indirect peer aggression during the transition to high school
Authors: Tarlow Naomi , La Greca Annette M.
Published: August 2020

The primary purpose of this study was to evaluate the relationship between decreased empathy (i.e., cognitive and affective) and indirect and cyber peer aggression among Latinx adolescents during their transition to high school. Further, we examined the degree to which social anxiety moderated this relationship. Participants were 469 Latinx ninth graders, ages 13–17 years (M = 14.52, SD = 0.58; 58% girls). Adolescents completed the Revised Peer Experiences Questionnaire, Cyber Peer Experiences Questionnaire, Basic Empathy Scale, and Social Anxiety Scale for Adolescents at two different time points, 3 months apart. Hierarchical linear regression analyses revealed concurrent and prospective relationships between lower cognitive empathy and the perpetration of both indirect and cyber aggression. In addition, social anxiety moderated the concurrent associations between both types of empathy and both types of aggression perpetration. Results suggest that interventions that facilitate cognitive empathy and decrease social anxiety may help to reduce adolescents' indirect and cyber aggression toward peers throughout the high school transition.
Is the association between childhood maltreatment and aggressive behavior mediated by hostile attribution bias in women? A discordant twin and sibling study
Authors: Johansson Ada , Rötkönen Nicola , Jern Patrick
Published: August 2020

Understanding the mechanisms behind aggressive behavior (AGG) is vital so that effective prevention and intervention strategies can be developed. Maltreated children are hypothesized to be prone to social information processing biases, such as hostile attribution bias (HAB), which, in turn, may increase the likelihood of behaving aggressively. The first aim of the present study was to replicate findings regarding associations between childhood maltreatment (CM), HAB, and aggression in a population‐based sample of Finnish female twins and their sisters (N = 2,167). However, these associations might not be causal but instead confounded by familial factors, shared between the variables. The second aim was, thus, to test the associations when potential confounding by familial (genetic or common environmental) effects were controlled for using a multilevel discordant twin and sibling design within (a) 379 pairs of twins (npairs = 239) or siblings (npairs = 140), and (b) within the 131 monozygotic (MZ) twin pairs. Consistent with previous studies, HAB mediated the association between CM and AGG when familial confounding was uncontrolled. No support was found for the mediation when controlling for familial confounding. Between‐pair associations were found between CM and AGG, and between CM and HAB. In addition, within‐pair associations were found between HAB and AGG, and between CM and AGG, however, these were nonsignificant in the discordant MZ analysis, offering the most stringent control of familial confounding. The results indicate the necessity of taking familial confounding into account when investigating the development of AGG.
Foot Osteoarthritis Frequency and Associated Factors in a Community‐Based Cross‐Sectional Study of White and African American Adults
Authors: Flowers Portia , Nelson Amanda E. , Hannan Marian T. , Hillstrom Howard J. , Renner Jordan B. , Jordan Joanne M. , Golightly Yvonne M.
Published: August 2020

Objective

Few studies have explored foot osteoarthritis (OA) in the general population. The purpose of this study was to determine the frequency of foot OA and identify associated factors in a cross‐sectional analysis of a large community‐based cohort.

Methods

Data were from the 2013–2015 study visit of the Johnston County OA Project. Radiographic OA of the foot was defined using the La Trobe radiographic atlas (≥2 osteophytes or joint space narrowing in at least 1 of 5 joints). Symptomatic OA of the foot was defined as foot radiographic OA with pain, aching, or stiffness in the same foot. At the foot‐level, separate logistic regression models with generalized estimating equations to account for intraperson correlations were performed to examine associations of foot radiographic OA or symptomatic OA with age, body mass index (BMI), sex, race, educational attainment, and previous foot injury.

Results

Of 864 participants with available data (mean age 71 years, mean BMI 30 kg/m2, 68% women, 33% African American, 13% <12 years of schooling), 22% had foot radiographic OA, 20% had foot symptoms, and 5% had foot symptomatic OA. Radiographic, but not symptomatic, foot OA was more common in African American than White participants. Participants with obesity, compared to normal weight, had >2 times the odds of radiographic OA and >5 times the odds of symptomatic OA in adjusted models.

Conclusion

Foot radiographic OA and foot symptoms were common in the sample, but both conditions simultaneously (i.e., symptomatic OA) occurred infrequently. Notably, obesity was linked with foot symptomatic OA, perhaps implicating metabolic or mechanical influences.
Adaptation of American College of Rheumatology Rheumatoid Arthritis Disease Activity and Functional Status Measures for Telehealth Visits
Authors: England Bryant R. , Barber Claire E. H. , Bergman Martin , Ranganath Veena K. , Suter Lisa G. , Michaud Kaleb
Published: August 2020

Objective

To provide guidance on the implementation of recommended American College of Rheumatology (ACR) rheumatoid arthritis (RA) disease activity and functional status assessment measures in telehealth settings.

Methods

An expert panel was assembled from the recently convened ACR RA disease activity and functional status measures working groups to summarize strategies for implementation of ACR‐recommended RA disease activity (the Clinical Disease Activity Index [CDAI], Disease Activity Score in 28 joints using the erythrocyte sedimentation rate or the C‐reactive protein level [DAS28‐ESR/CRP], Patient Activity Scale II [PAS‐II], Simplified Disease Activity Index [SDAI], and Routine Assessment of Patient Index Data 3 [RAPID3]) and functional status (the Health Assessment Questionnaire II [HAQ‐II], Multidimensional Health Assessment Questionnaire [MDHAQ], and PROMIS physical function 10‐item short form [PROMIS PF‐10]) measures in telehealth settings.

Results

Measures composed of patient‐reported items (disease activity: PAS‐II, RAPID3; functional status: HAQ‐II, MDHAQ, PROMIS PF‐10) require minimal modification for use in telehealth settings. Measures requiring formal joint counts (the CDAI, DAS28‐ESR/CRP, and SDAI) can be calculated using patient‐reported swollen and tender joint counts. When the feasibility of laboratory testing is limited, the CDAI can be used in place of the SDAI, and scoring modifications of the DAS28‐ESR/CRP without the acute‐phase reactant are available. Assessment of the validity of these modifications is limited. Implementation of these measures can be facilitated by electronic health record collection, mobile applications, and provider/staff administration during telehealth visits.

Conclusion

The ACR‐recommended RA disease activity and functional status measures can be adapted for use in telehealth settings to support high‐quality clinical care. Research is needed to better understand how telehealth settings may impact the validity of these measures.
Inkjet Printing of Bioresorbable Materials for Manufacturing Transient Microelectronic Devices
Authors: Mitra Kalyan Y. , Willert Andreas , Chandru Roshan , Baumann Reinhard R. , Zichner Ralf
Published: August 2020

Herein, the inkjet printing of bioresorbable materials tuned to function as electrode, dielectric, and semiconductor layers is reported, thereby developing multilayered microelectronic devices such as capacitors and thin‐film transistors, potentially applicable to address specific medical needs. Polymers and natural materials, e.g., poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate), shellac, and β‐carotene, indigo inks are implemented using jettable formulations, that are either commercially procured or self‐formulated, designed explicitly to deposit fundamental layers for capacitors and transistors. Several parameters are evaluated and adjusted to precisely define a layer's thickness, topology, and geometry, matching with the properties of a fully biodegradable Ormocere substrate, explicitly developed for the specific biological applications. Furthermore, these parameters support in acquiring the intended electrical properties of layers, i.e., conductivity, insulation, semiconductivity, capacitance, and current versus voltage characteristics. The entire manufacturing process of devices is accomplished on the Ormocere substrate under ambient conditions and below 60 °C. The results exhibit that the electrical characteristics of the printed functional layers and devices show direct influence to the physical geometry of the printed features. A fully printed capacitor demonstrates capacitance of 1 nF cm−2, whereas transistors show p‐type and n‐type characteristics with current 0.18–5 μA and mobility 6 × 10−4–7 × 10−2 cm2 V−1 s−1.
Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors
Authors: Lee Yunki , Choi Jeongmoon J. , Ahn Song Ih , Lee Nan Hee , Han Woojin M. , Mohiuddin Mahir , Shin Eun Jung , Wood Levi , Park Ki Dong , Kim YongTae , Jang Young C.
Published: August 2020

Exposure of a young systemic milieu reveals remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been reported, the exact underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the experimental challenges of using in vivo parabiosis. An in vitro parabiosis system is reported here that integrates young‐ and old‐muscle stem cell vascular niche on a 3D microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This 3D micro‐physiological system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. Using engineered parabiosis system, it is demonstrated that vascular endothelial growth factor signaling from endothelial cells and myotubes synergistically contributes to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on‐chip system, both blood transfusion and parabiosis can be mimicked and the time‐varying effects of antigeronic and progeronic factors can be monitored in a single organ or multiorgan systems. The microfluidic system can be utilized as a complementary in vitro microphysiological model to aid the complex in vivo parabiosis studies.
Emerging Metal Single Atoms in Electrocatalysts and Batteries
Authors: Ma Lianbo , Zhu Guoyin , Wang Dandan , Chen Huixian , Lv Yaohui , Zhang Yizhou , He Xiaojun , Pang Huan
Published: August 2020

Energy conversion and storage applications require highly stable and efficient electrocatalysts/electrodes to facilitate electrochemical reactions, but these materials commonly suffer from serious atom wastes and lower performances than the theoretical levels, which cannot meet the increasing demands of the green atomic economy, thereby limiting their practical applications. Recently, metal single atoms (SAs) have attracted tremendous attention owing to their merits of full atom utilization, unique electronic structures, tunable surface characteristics, and low costs. However, metal SAs usually have relatively low physical/chemical stabilities due to their high surface energy, which results in severe degradation of electrochemical performances. Novel synthetic strategies are developed for metal SAs with better stability and performance. In this review, these strategies will be introduced in the context of electrocatalysis and batteries. Specifically, the design concepts, synthesis approach properties, and applications of metal SAs will be discussed. Finally, the critical challenges and future perspectives of metal SAs are presented. This review aims to provide new insights for future work as well as the real‐world applications of metal SAs.
A Biomimetic Nano‐Engineered Platform for Functional Tissue Engineering of Cartilage Superficial Zone
Authors: Dehghan‐Baniani Dorsa , Mehrjou Babak , Chu Paul K. , Wu Hongkai
Published: August 2020

Articular cartilage has limited regeneration capacity because of its acellular and avascular nature. Although tissue engineering has been shown to be life‐saving, reforming cartilage zones required by the appropriate tissue functions are challenging. Herein, the need is addressed by designing and producing a nano‐engineered structure mimicking the superficial zone (SZ) of articular cartilage. The substrate is based on silk with good mechanical properties in conjunction with nano‐topographical and biochemical cues. Nanopillar arrays are produced on the silk surface to regulate the stem cell morphology rendering them with a flattened ellipsoidal shape that is similar to that of chondrocytes in the SZ of natural cartilage. The cell interactions are enhanced by nitrogen ion implantation and the biomolecule, kartogenin (KGN), is loaded to promote chondrogenesis of the stem cells and furthermore, a thermosensitive chitosan hydrogel is formed on the nanopatterned silk to produce rheological properties similar to those of a synovial fluid. Based on the in vitro results and mechanical properties, it is a desirable implantable smart structure mimicking the cartilage SZ with the ability of continuous drug release for cartilage regeneration.
A First‐Principles‐Based Sub‐Lattice Formalism for Predicting Off‐Stoichiometry in Materials for Solar Thermochemical Applications: The Example of Ceria
Authors: Sai Gautam Gopalakrishnan , Stechel Ellen B. , Carter Emily A.
Published: August 2020

Theoretical models that reliably can predict off‐stoichiometry in materials via accurate descriptions of underlying thermodynamics are crucial for energy applications. For example, transition‐metal and rare‐earth oxides that can tolerate a large number of oxygen vacancies, such as CeO2 and doped CeO2, can split water and carbon dioxide via a two‐step, oxide‐based solar thermochemical (STC) cycle. The search for new STC materials with a performance superior to that of state‐of‐the‐art CeO2 can benefit from predictions accurately describing the thermodynamics of oxygen vacancies. The sub‐lattice formalism, a common tool used to fit experimental data and build temperature‐composition phase diagrams, can be useful in this context. Here, sub‐lattice models are derived solely from zero‐temperature quantum mechanics calculations to estimate fairly accurate temperature‐ and oxygen‐partial‐pressure‐dependent off‐stoichiometries in CeO2 and Zr‐doped CeO2. Physical motivations for deriving some of the “excess” sub‐lattice model parameters directly from quantum mechanical calculations, instead of fitting to minimize deviations from experimental and/or theoretical data, are identified. Important limitations and approximations of the approach used are specified and extensions to multi‐cation oxides are also suggested to help identify novel candidates for water and carbon dioxide splitting and related applications.
Durch Nitro‐ und andere elektronenziehende Gruppen aktivierte Ruthenium‐Katalysatoren für die Olefinmetathese
Authors: Kajetanowicz Anna , Grela Karol
Published: August 2020

Fortschrittliche Anwendungen der mit dem Nobelpreis ausgezeichneten Olefinmetathese erfordern nutzerfreundliche Handhabung und vielseitig anwendbare Katalysatoren. Unter den zahlreichen bekannten Metathesekatalysatoren, welche zu den zwei Klassen der Schrock‐ und Grubbs‐Katalysatoren gehören, bietet die Untergruppe der chelatisierten Rutheniumbenzyliden‐Komplexe (auch genannt Hoveyda‐Grubbs‐Katalysatoren) durch zusätzliche Aktivierung durch elektronenziehende Gruppen (EWG) eine hochgradig abstimmbare Plattform. Im vorliegenden Aufsatz werden der Ursprung des EWG‐Aktivierungskonzeptes und ausgewählte Anwendungen der resultierenden Katalysatoren in zielgerichteten Synthesen, im Bereich der medizinischen Chemie sowie in der Herstellung von Feinchemikalien und der Materialchemie erörtert. Darauf basierend werden dem Anwender einige Vorschläge hinsichtlich der Minimierung der Katalysatorbeladung, der Selektivitätskontrolle und allgemeine Optimierungshinweise der Olefinmetathese gegeben.
A Next‐Generation Air‐Stable Palladium(I) Dimer Enables Olefin Migration and Selective C−C Coupling in Air
Authors: Kundu Gourab , Sperger Theresa , Rissanen Kari , Schoenebeck Franziska
Published: August 2020

We report a new air‐stable PdIdimer, [Pd(μ‐I)(PCy2tBu)]2, which triggersE‐selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C−C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C−Br, C−OTf/OFs, and C−Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous PdIdimer generations for substrates that bear substituentsorthoto C−OTf.
Desoxyfluorierung von Phosphanoxiden: Ein allgemeiner Weg zu fluorierten Organophosphor(V)‐Verbindungen und noch mehr
Authors: Bornemann Dustin , Pitts Cody Ross , Wettstein Lionel , Brüning Fabian , Küng Sebastian , Guan Liangyu , Trapp Nils , Grützmacher Hansjörg , Togni Antonio
Published: August 2020

Fluorierte Organophosphor(V)‐Spezies sind eine vielseitige Klasse von Verbindungen. Ihre aktuell zur Verfügung stehenden Synthesemethoden haben jedoch die Nachteile der gelegentlichen Handhabung von toxischen oder pyrophoren PIII‐Ausgangsmaterialien und der Abhängigkeit von gefährlichen Fluorierungsreagenzien wie XeF2. Wir präsentieren hier eine alternative Methode zur Lösung dieser Probleme mittels Desoxyfluorierung (DOF) von einfach zu gebrauchenden Phosphanoxiden als Ausgangsmaterialien und vermeiden gleichzeitig aggressive Fluorierungsreagenzien durch eine Kombination von Oxalylchlorid und Kaliumfluorid. Die Reaktion hat sich als allgemein anwendbar erwiesen, da R3PF2‐, R2PF3‐ und RPF4‐Verbindungen (sowie verschiedene davon abgeleitete Kationen und Anionen) in guten Ausbeuten und im Multi‐Gramm‐Maßstab zugänglich sind. DFT‐Berechnungen wurden verwendet, um unsere Beobachtungen zu untermauern. Insbesondere führte die Entdeckung dieser neuen Methode zu einer bequemen Synthese von 1) neuen Difluorphosphoniumionen, 2) Hexafluorphosphatsalzen und 3) fluorierten Antimon‐ und Arsenverbindungen.
Intratumor heterogeneity: A new perspective on colorectal cancer research
Authors: Zheng Zicheng , Yu Tao , Zhao Xinyu , Gao Xin , Zhao Yao , Liu Gang
Published: August 2020

Colorectal cancers generally consist of multiple subclones. These subclones have their own unique characteristics, resulting in intratumor heterogeneity (ITH). As the discussion of ITH has advanced, a model describing the relationship of ITH to the tumor has gradually emerged. ITH can be divided into two types of intraprimary tumor heterogeneity and intraindividual tumor heterogeneity, the former for further understanding of tumor composition, and the latter for providing more information about evolutionary patterns. With the rapid development of new methods, such as next‐generation, polyguanine region sequencing, and Image detection, researchers may unravel the secrets underlying ITH. The higher the ITH of the tumor, the richer the interaction between the subclones maybe, or the greater the chance of the tumor getting more powerful subclones may be, thus increasing the malignant potential of the tumor. Existing evidence suggests that ITH may increase the ability of tumors to resist treatment and can be used as an independent influence on the prognosis of colorectal cancer. We reviewed 80 recent studies to give researchers a new perspective on colorectal cancer. There is still a limited amount of research in this area. Further study of the relationship between ITH and clinical endpoints may lead to the development of new treatment strategies.
CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR‐541‐3p/GPX4 axis
Authors: Xu Qinhong , Zhou Lijing , Yang Ganghua , Meng Fandi , Wan Yong , Wang Lin , Zhang Lei
Published: August 2020

Ferroptosis is a specific iron‐dependent cell death form that can induce the production of lipid peroxide, but the roles of circular RNAs (circRNAs) in ferroptosis are completely unaware. Circ‐interleukin‐4 receptor (circIL4R) was reported to express highly in hepatocellular carcinoma (HCC). This study focused on the function of circIL4R dysregulation in tumor progression and ferroptosis of HCC, as well as its molecular mechanism. The quantitative real‐time polymerase chain reaction was implemented for measuring RNA expression. Cell proliferation and survival were evaluated using 3‐(4,5‐dimethylthiazol‐2‐y1)‐2,5‐diphenyl tetrazolium bromide. Apoptotic cells were detected via flow cytometry. The quantification of protein expression was executed through western blotting analysis. The target binding was assessed via the dual‐luciferase reporter, RNA immunoprecipitation, and RNA pull‐down assays. The experiment in vivo was performed using a xenograft model. CircIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA‐541‐3p (miR‐541‐3p) and miR‐541‐3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR‐541‐3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR‐541‐3p‐induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR‐541‐3p/GPX4 axis in vivo. Our data suggested that circIL4R served for a tumor promoter and ferroptosis inhibitor in HCC by the miR‐541‐3p/GPX4 network.
High‐glucose concentration aggravates TNF‐alpha‐induced cell viability reduction in human CD146‐positive periodontal ligament cells via TNFR‐1 gene demethylation
Authors: Luo Haoyuan , Zhu Wenjun , Mo Weiyan , Liang Min
Published: August 2020

Periodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high‐glucose concentrations aggravate cell viability reduction in human CD146‐positive PDLCs (CD146+PDLCs) under tumor necrosis factor‐alpha (TNF‐alpha) induction. CD146+PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10 ng/ml of TNF‐alpha and 30 mM glucose. Cell viability was detected using Cell Counting Kit‐8 assays and Luminescent Cell Viability Assays. Western blotting and real‐time polymerase chain reaction were performed to determine tumor necrosis factor‐alpha receptor‐1 (TNFR‐1) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR‐1 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high‐glucose concentration and TNF‐alpha. Treatment with 30 mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR‐1. Additionally, we found that the CpG island located within the TNFR‐1 gene was hypomethylated under 30 mM glucose conditions. S‐adenosylmethionine, an established methyl donor, reversed TNFR‐1 upregulation and restored cell viability against high‐glucose concentration and TNF‐alpha. In conclusion, the present findings suggest that high‐glucose‐induced CpG island hypomethylation within the TNFR‐1 gene plays an essential role in TNFR‐1 upregulation, and this further enhances the cell viability reduction of CD146+PDLCs caused by TNF‐alpha.
Circular RNA PRMT5 confers cisplatin‐resistance via miR‐4458/REV3L axis in non‐small‐cell lung cancer
Authors: Pang Jun , Ye Liwen , Zhao Dan , Zhao Ding , Chen Qingwei
Published: August 2020

Multifactor and multistep processes were elucidated to participate in the progression of non‐small‐cell lung cancer (NSCLC). Circular RNA 0031250 (circ‐PRMT5) was a vital factor in NSCLC. However, the role of circ‐PRMT5 in cisplatin (DDP)‐resistance needed to be further highlighted. Expression profiles of circ‐PRMT5, microRNA (miR)‐4458, and EV3‐like DNA‐directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real‐time polymerase chain reaction. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half‐maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual‐luciferase reporter assay was performed to analyze the interaction between miR‐4458 and circ‐PRMT5 or REV3L. The functional role of circ‐PRMT5 was explored using a xenograft tumor model. Levels of circ‐PRMT5 and REV3L were markedly increased, while miR‐4458 was downregulated in resistant tissues and cells. Knockdown of circ‐PRMT5 enhanced cell apoptosis, DDP‐sensitivity, and declined metastasis in NSCLC with DDP resistance. Besides, miR‐4458 inhibition or REV3L upregulation could revert circ‐PRMT5 absence‐mediated effect on DDP‐sensitivity in vitro. Mechanically, circ‐PRMT5 was a sponge of miR‐4458 to regulate REV3L. Importantly, circ‐PRMT5 silencing could interact with DDP treatment expedite the decrease of tumor growth in vivo. Circ‐PRMT5 promoted DDP resistance via REV3L by sponging miR‐4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC.
Clinical implication of neointimal burden in in‐stent restenosis treated with drug‐coated balloon
Authors: Lee Jung‐Hee , Kim Ung , Kim Jung‐Sun , Hong Sung‐Jin , Ahn Chul‐Min , Kim Byeong‐Keuk , Ko Young‐Guk , Choi Donghoon , Hong Myeong‐Ki , Jang Yangsoo
Published: August 2020

Background

Although drug‐coated balloon (DCB) angioplasty is a well‐established drug‐eluting stent (DES) in‐stent restenosis (ISR) strategy, there are minimal data regarding the association of neointimal burden on optical coherence tomography (OCT) before and after DCB and adverse clinical events. This study aimed to investigate the clinical impact of neointimal burden measured with OCT in patients with DES ISR after DCB angioplasty.

Methods

From 2010 through 2013, a total of 122 patients with 122 ISR lesions were treated with DCB, which was preceded and followed by OCT examination. Major adverse cardiac events (MACE, a composite occurrence of cardiovascular cardiac death, nonfatal myocardial infarction [MI], or target lesion revascularization [TLR]) were evaluated.

Results

MACE occurred in 27 patients (4 nonfatal MIs and 23 TLRs) during the follow‐up (median: 55.3 months, interquartile range 43.1–66.0). The mean lumen area was significantly smaller (3.21 ± 2.42 mm2 vs. 4.80 ± 2.53 mm2, p = .005) and the mean percentage of neointimal volume derived by OCT was greater (49.3 ± 9.2% vs. 38.3 ± 17.5%, p = .006) in patients with MACE before DCB angioplasty. The pre‐procedural mean percentage of neointimal volume (cut‐off 50%, area under the receiver operating characteristic [ROC] curve = 0.644, 95% confidence interval [CI] = 0.531–0.758, p = .022) and post‐procedural mean percentage of neointimal volume (cut‐off 25%, area under ROC curve = 0.659, 95% CI = 0.546–0.773, p = .012) were identified as significant parameters to predict MACE.

Conclusion

The OCT‐derived mean percentages of neointimal volume before and after DCB angioplasty can be important parameters for predicting future MACE in patients with DES ISR.
High‐Energy Proton‐Beam‐Induced Polymerization/Oxygenation of Hydroxynaphthalenes on Meteorites and Nitrogen Transfer from Urea: Modeling Insoluble Organic Matter?
Authors: Bizzarri Bruno Mattia , Manini Paola , Lino Valeria , d'Ischia Marco , Kapralov Michail , Krasavin Eugene , Mráziková Klaudia , Šponer Jiří , Šponer Judit E. , Di Mauro Ernesto , Saladino Raffaele
Published: August 2020

Formation and structural modification of oxygenated polycyclic aromatic hydrocarbons (oxyPAHs) by UV irradiation on minerals have recently been proposed as a possible channel of PAH transformation in astrochemical and prebiotic scenarios of possible relevance for the origin of life. Herein, it is demonstrated that high‐energy proton‐beam irradiation in the presence of various meteorites, including stony iron, achondrite, and chondrite types, promotes the conversion of two representative oxyPAH compounds, 1‐naphthol and 1,8‐dihydroxynaphthalene, to complex mixtures of oxygenated and oligomeric derivatives. The main identified products include polyhydroxy derivatives, isomeric dimers encompassing benzofuran and benzopyran scaffolds, and, notably, a range of quinones and perylene derivatives. Addition of urea, a prebiotically relevant chemical precursor, expanded the range of identified species to include, among others, quinone diimines. Proton‐beam irradiation of oxyPAH modulated by nitrogen‐containing compounds such as urea is proposed as a possible contributory mechanism for the formation and processing of insoluble organic matter in meteorites and in prebiotic processes.
Do single‐stock circuit breakers provide a safety net for Canadian investors?
Authors: Switzer Lorne N. , El Meslmani Nabil , Tahaoglu Cagdas
Published: August 2020

This study looks at the market impact of recent regulatory changes in Canada that provide for trading halts on individual stocks that experience large upside or downside movements. The focus is on all stocks traded on the Toronto Stock Exchange since the inception of the single‐stock circuit breaker rule (SSCB) in February 2012, to replace the short‐sale uptick rule. The results support pricing efficiency: material information that caused the circuit breaker is incorporated in stock prices on the day of the halt (neither overreaction nor underreaction), with no decline in market liquidity. Using trade‐by‐trade data constructed on five‐minute trading intervals, we refine the daily results, and show that shocks in realized volatility are focused in the 10‐minute trading interval surrounding the halts. While circuit breakers provide a limited safety net for investors when their stocks are subject to severe volatility, they do not allow for a quick turnaround for stocks experiencing severe price decline events.
Characterization of spray paints used in street art graffiti by a non‐destructive multi‐analytical approach
Authors: Cortea Ioana Maria , Ratoiu Lucian , Rădvan Roxana
Published: August 2020

Often associated with acts of vandalism, graffiti can also be identified with the so‐called street art movement. Moreover, in the historical context of visual arts from the 20th and 21st century, graffiti spray paints feature among the materials employed in the work of representative artists such as Lucio Fontana, Richard Hamilton, Yves Klein, or David Alfaro Siqueiros. In this study, a large number of artist spray paints were analyzed by means of X‐Ray Fluorescence (XRF), Fourier Transform Infrared Spectroscopy (FTIR), spectrophotometry, and Hyperspectral Imaging (HSI). The aim of the study was to provide a chemical characterization of the main organic and inorganic components present within the spray paint formulations by means of a complementary non‐destructive approach. Titanium white, zinc white, bismuth vanadate yellow, ultramarine, strontium sulfide, iron, and copper oxides, along a series of pigments of the azo, phthalocyanine, and quinacridone classes could be identified. High amounts of barium sulfate as well as calcium‐based extenders were also detected. FTIR analysis provided important information regarding the binder composition, mainly modified alkyd resins being identified. Additional information related to the existing chromophores as well as specific binder‐pigments interactions could also be highlighted within the HSI data sets. Overall results provide new insights on the complex chemistry of this new range of materials, which could help future investigations carried on street art graffiti, contemporary murals, or mixed‐media artworks.
Haemoglobin A1c is a predictor of COVID‐19 severity in patients with diabetes
Authors: Merzon Eugene , Green Ilan , Shpigelman Miriam , Vinker Shlomo , Raz Itamar , Golan‐Cohen Avivit , Eldor Roy
Published: August 2020

Aim

Poor outcomes of coronavirus disease 2019 (COVID‐19) have been linked to diabetes, but its relation to pre‐infection glycaemic control is still unclear.

Materials and Methods

To address this question, we report here the association between pre‐infection Haemoglobin A1c (HbA1c) levels and COVID‐19 severity as assessed by need for hospitalization in a cohort of 2068 patients with diabetes tested for COVID‐19 in Leumit Health Services (LHSs), Israel, between 1 February and 30 April 2020. Using the LHS‐integrated electronic medical records system, we were able to collect a large amount of clinical information including age, sex, socio‐economic status, weight, height, body mass index, HbA1c, prior diagnosis of ischaemic heart disease, depression/anxiety, schizophrenia, dementia, hypertension, cerebrovascular accident, congestive heart failure, smoking, and chronic lung disease.

Results

Of the patients included in the cohort, 183 (8.85%) were diagnosed with COVID‐19 and 46 were admitted to hospital. More hospitalized patients were female, came from higher socio‐economic background and had a higher baseline HbA1c. A prior diagnosis of cerebrovascular accident and chronic lung disease conferred an increased risk of hospitalization but not obesity or smoking status. In a multivariate analysis, controlling for multiple prior clinical conditions, the only parameter associated with a significantly increased risk for hospitalization was HbA1c ≥ 9%.

Conclusion

Using pre‐infection glycaemic control data, we identify HbA1c as a clear predictor of COVID‐19 severity. Pre‐infection risk stratification is crucial to successfully manage this disease, efficiently allocate resources, and minimize the economic and social burden associated with an undiscriminating approach.
Detection and identification of ACP‐105 and its metabolites in equine urine using LC/MS/MS after oral administration
Authors: Subhahar Michael Benedict , Karakka Kal Abdul Khader , Philip Moses , K. Karatt Tajudheen , N. Ibrahimwaseem , Vazhat Ramees Abdulla , M.P. Muhammed Ajeebsanu
Published: August 2020

ACP‐105 is a novel nonsteroidal selective androgen receptor modulator (SARM) with a tissue‐specific agonist effect and does not have side effects associated with the use of common androgens. This research reports a comprehensive study for the detection of ACP‐105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP‐105, a selective and reliable LC‐MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of 19 metabolites were detected in ACP‐105 drug administered equine urine samples. The study results suggest the following: (1) ACP‐105 is prone to oxidation, which gives corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the third position of the tropine moiety, resulting in the dehydrated analogs of corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (3) from the study on the metabolites using LC‐MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP‐105 and its metabolites were detected for up to 72 h; thus, the result is a valuable tool for evaluating its use and/or misuse in sport.
Formation of the rete testis during mouse embryonic development
Authors: Kulibin Andrey Yu. , Malolina Ekaterina A.
Published: August 2020

Background

The rete testis connects seminiferous tubules of the testis with efferent ducts having a mesonephric origin. The development of the rete testis is insufficiently studied, but there is evidence suggesting that it originates from gonadal cells. Here, the formation of the rete testis was investigated from E11.5 to E16.5 using immunofluorescent staining and 3D‐modeling.

Results

The rete testis became visible by SOX9 and PAX8 staining starting from E12.5. It was located in the mesonephros but connected with testis cords formed by Sertoli cells expressing SOX9, AMH, DMRT1. Between E13.5 and E14.5, AMH+ network of testis cords at the mesonephric side began to disintegrate in a gradient‐dependent manner along the anterior‐posterior axis of the gonad and connections between testis cords gradually lost AMH becoming a part of the rete. Cells combining features of Sertoli and rete cells (PAX8+ AMH+ and DMRT1+ AMH− cells) were detected starting from E14.5, suggesting that some rete cells originated from Sertoli cells. The rete ovarii, a female counterpart of the rete testis, developed in a similar way as the rete testis until E13.5.

Conclusions

A part of the rete testis originates from connections between testis cords. Evidence that Sertoli cells contribute to rete cells is provided.
Expander design procedures and selection criterion for small rated organic rankine cycle systems
Authors: Capata Roberto , Pantano Fabio
Published: August 2020

The particular aspect of this work is the new approach to expander design procedure for small rated ORC. In fact, once all the calculation procedures have been defined, they have been implemented in Matlab code. This code, once the design process is complete, provides an indication of the optimal expander configuration to adopting to that specific system. For these reasons, this paper aims to analyze all the preliminary expanders' design procedures, both dynamic and volumetric. The reasons lie in the development of low‐enthalpy heat recovery systems (systems that allow simultaneous production of electrical and thermal energy made available in the form of water at a temperature of 60‐90°C), with the aim of optimizing any energy system. Within these energy systems, the expander is the main component, responsible for power generation. It is, therefore, necessary and useful to analyze in detail every expander configuration, highlighting the different features. For each component will be described the theory on which is based the choice and its design and a possible software implementation is supplied. Finally, a criterion for the choice of the optimal expander is proposed, based on some operational considerations and other construction and structural constraints, such as overall dimensions and weight, lubrication, MTBF, feasibility, reliability, and coupling with the electric generator.
Bipolar fully recurrent deep structured neural learning based attack detection for securing industrial sensor networks
Authors: Alzubi Jafar A.
Published: August 2020

Attack detection is a significant problem to be resolved to attain security in industrial sensor network. Few research works have been designed for performing attack discovery process with the help of different classification algorithms. However, classification performance was lowered to accurately find attack nodes and thereby getting higher security level (SL). In order to overcome such limitations, bipolar fully recurrent deep structured neural learning based attack detection (BFRDSNL‐AD) technique is proposed in this article. The BFRDSNL‐AD technique comprises of three main layers, namely, input, hidden, and output layer to accurately carry‐out attack detection process. The input layer in BFRDSNL‐AD Technique takes a number of sensor nodes as input. The designed BFRDSNL‐AD technique utilized numbers of hidden layers in order to deeply examine each sensor node in industrial sensor network. The result of the hidden layer is fed‐back into the network along with the inputs in order to discover the temporal dynamic behavior of sensor nodes. In BFRDSNL‐AD technique, output layer applies bipolar activation function to determine the association between identified node features to give attack detection result. If the output layer result is 1, then sensor node is considered as normal. Otherwise, sensor node is considered as malicious attack in industrial sensor network. Thus, the BFRDSNL‐AD technique increases the attack detection performance with higher accuracy and minimal time. From that, BFRDSNL‐AD technique gets enhanced SL in industrial sensor network. The simulation of BFRDSNL‐AD technique is conducted using metrics such as security, data delivery rate, data loss rate, and delay with respect to a different number of sensor nodes and data packets.
Dispergierung beim Hydroschildvortrieb
Authors: Weiner Thorsten , Thewes Markus
Published: August 2020

In this contribution the relevance of dispersion for tunnel construction will be demonstrated on the basis of project experience and an exemplary economic consideration. The authors recommend application of the recently developed test for the prediction of dispersion as well as more intensive use of the corresponding contractual mechanism.