bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐378a‐3p as a putative biomarker for hepatocellular carcinoma diagnosis and prognosis: Computational screening with experimental validation
Authors: Qian Fuliang , Wang Jinghan , Wang Ying , Gao Qian , Yan Wenying , Lin Yuxin , Shen Li , Xie Yufeng , Jiang Xiaoqing , Shen Bairong 
Published: February 2021

AbstractBackgroundHepatocellular carcinoma (HCC) is a malignant disease with high morbidity and mortality, and the molecular mechanism for the genesis and progression is complex and heterogeneous. Biomarker discovery is crucial for the personalized and precision treatment of HCC. The accumulation of reported microRNA biomarkers makes it possible to combine computational identification with experimental validation to accelerate the discovery of novel biomarker.ResultsIn the present work, we applied a rational computer‐aided biomarker discovery model to screen for the HCC diagnosis biomarker. Two HCC‐associated networks were constructed based on the microRNA and mRNA expression profiles, and the potential microRNA biomarkers were identified based on their unique regulatory and influential power in the network. These putative biomarkers were then experimentally validated. One prominent example among these identified biomarkers is MiR‐378a‐3p: It was shown to independently regulate several important transcription factors such as PLAGL2 and β‐catenin, affecting the β‐catenin signaling. Such mechanism may indicate a potential tumor suppressor role of MiR‐378a‐3p and the impact of its abnormal expression on the cell growth and invasion of HCC.ConclusionsA bioinformatics model with network topological and functional characterization was successfully applied to the identification of HCC biomarkers. The predicted microRNA biomarkers were than validated with experiments using human HCC cell lines, model animal, and clinical specimens. The results confirmed the prediction by our proposed model that miR‐378a‐3p was a putative biomarker for diagnosis and prognosis of HCC.
FAM83H‐AS1 is a noncoding oncogenic driver and therapeutic target of lung adenocarcinoma
Authors: Wang Siwei , Han Chencheng , Liu Tongyan , Ma Zhifei , Qiu Mantang , Wang Jie , You Qingjun , Zheng Xiufen , Xu Weizhang , Xia Wenjia , Xu Youtao , Hu Jingwen , Xu Lin , Yin Rong 
Published: February 2021

AbstractBackgroundLittle is known about noncoding oncogenes of lung adenocarcinoma (LUAD), and these potential drivers might provide novel therapeutic targets.MethodsSince abnormally overexpression of oncogenic drivers is induced by genomic variation, we here utilized genomic, transcriptomic, and clinical prognosis data of The Cancer Genome Atlas (TCGA) LUAD datasets to discover novel drivers from long noncoding RNAs. We further used zebrafish models to validate the biological function of candidates in vivo. The full length of FAM83H‐AS1 was obtained by rapid amplification of the cDNA ends assay. RNA pull‐down, RNA immunoprecipitation, quantitative mass spectrometry, and RNA sequencing assays were conducted to explore the potential mechanisms. Additionally, we used CRISPR interference (CRISPRi) method and patient‐derived tumor xenograft (PDTX) model to evaluate the therapeutic potential of targeting FAM83H‐AS1.ResultsThe results suggest that FAM83H‐AS1 is a potential oncogenic driver due to chromosome 8q24 amplification. Upregulation of FAM83H‐AS1 results in poor prognosis of LUAD patients in both Jiangsu Cancer Hospital (JSCH) and TCGA cohorts. Functional assays revealed that FAM83H‐AS1 promotes malignant progression and inhibits apoptosis. Mechanistically, FAM83H‐AS1 binds HNRNPK to enhance the translation of antiapoptotic oncogenes RAB8B and RAB14. Experiments using CRISPRi‐mediated xenografts and PDTX models indicated that targeting FAM83H‐AS1 inhibited LUAD progression in vivo.ConclusionsOur work demonstrates that FAM83H‐AS1 is a noncoding oncogenic driver that inhibits LUAD apoptosis via the FAM83H‐AS1–HNRNPK–RAB8B/RAB14 axis, which highlights the importance and potential roles that FAM83H‐AS1 may serve as a novel therapeutic target for LUAD.
Spannungs‐Dehnungs‐Linien von Porenbeton bei hohen Temperaturen: ein erster Schritt zur versuchsbasierten Bemessung gemäß EN 1996‐1‐2
Authors: Andreini Marco , Miccoli Lorenzo 
Published: February 2021

AbstractIn diesem Beitrag wird ein Ansatz für die Bemessung von Mauerwerk aus Porenbeton unter Brandeinwirkung vorgestellt. Dabei wird die Problematik der Berechnungsmethoden in der aktuellen Fassung der EN 1996‐1‐2 für die Bemessung von tragenden Porenbetonwänden erläutert. Die aktuelle Version der EN 1996‐1‐2 bietet nur tabellarische Daten als verlässliche Methode für die Bewertung von Tragwerken im Brandfall. Die Inhalte der aktuellen Anhänge C und D gelten allgemein als nicht verlässlich für die Bemessung, da ein ausreichender Nachweis durch Versuche fehlt. Deshalb wird in diesem Beitrag eine Optimierung der Eingabegrößen für mechanische Modelle vorgeschlagen, die auf Prüfungen von Porenbetonmauerwerk basiert. Auf dieser Grundlage werden hier neue Spannungs‐Dehnungs‐Linien in Abhängigkeit von der Temperatur vorgeschlagen und anschließend mit den derzeit im Anhang D der EN 1996‐1‐2 enthaltenen Spannungs‐Dehnungs‐Linien verglichen. Die Resultate dieser Vergleiche zeigen, dass die derzeitigen Kennlinien nicht dem tatsächlichen Verhalten von Porenbetonmauerwerk im Brandfall entsprechen. Die hier vorgestellten Kennlinien können als Grundlage für die Umsetzung in der neuen Version der EN 1996‐1‐2 verwendet werden.
Einfluss des Hellbezugswertes auf die Risssicherheit von Außenwänden aus Porenbeton
Authors: Schoch Torsten , Loderer Franz , Trümer André 
Published: February 2021

AbstractDie Helligkeit einer Oberfläche beeinflusst die thermische Belastung einer Beschichtung und des darunter liegenden Mauerwerks oder Dämmstoffs. Vor allem dunkle Flächen mit niedrigem Hellbezugswert (HBW) heizen sich unter Sonneneinstrahlung stark auf. Bei Anwendung auf hochwärmedämmenden Untergründen wie Porenbeton kann die entstehende Wärme nicht ausreichend schnell abgegeben werden. Die Folge sind thermisch bedingte Spannungen zwischen Beschichtung und Untergrund. Aus diesem Grund empfehlen Hersteller eine Limitierung des Hellbezugswertes. Untersuchungen der Xella Technologie‐ und Forschungsgesellschaft mbH zeigen jedoch, dass auch dunkle Beschichtungen mit äußerst geringem HBW unter extremen Klimabedingungen weder selbst Schaden nehmen noch Schaden an der Porenbeton‐Tragschicht verursachen. Somit scheint der HBW als Referenz zur Begrenzung der thermischen Spannungen ungeeignet. Für dunkle Flächen empfehlen Hersteller von Beschichtungen daher weiterhin die Berücksichtigung des solaren Reflexionsvermögens (TSR‐Wert). Dieser Wert erfasst im Gegensatz zum HBW das gesamte Energiespektrum des Sonnenlichts und stellt somit eine pigmentunabhängige Kenngröße zur Beurteilung des Erwärmungspotenzials einer Beschichtung dar. Entsprechende Grenzwertbetrachtungen sind Gegenstand aktueller Untersuchungen.
Xenopus to the rescue: A model to validate and characterize candidate ciliopathy genes
Authors: Rao Venkatramanan G. , Kulkarni Saurabh S. 
Published: February 2021

SummaryCilia are present on most vertebrate cells and play a central role in development, growth, and homeostasis. Thus, cilia dysfunction can manifest into an array of diseases, collectively termed ciliopathies, affecting millions of lives worldwide. Yet, our understanding of the gene regulatory networks that control cilia assembly and functions remain incomplete. With the advances in next‐generation sequencing technologies, we can now rapidly predict pathogenic variants from hundreds of ciliopathy patients. While the pace of candidate gene discovery is exciting, most of these genes have never been previously implicated in cilia assembly or function. This makes assigning the disease causality difficult. This review discusses how Xenopus, a genetically tractable and high‐throughput vertebrate model, has played a central role in identifying, validating, and characterizing candidate ciliopathy genes. The review is focused on multiciliated cells (MCCs) and diseases associated with MCC dysfunction. MCCs harbor multiple motile cilia on their apical surface to generate extracellular fluid flow inside the airway, the brain ventricles, and the oviduct. In Xenopus, these cells are external and present on the embryonic epidermal epithelia, facilitating candidate genes analysis in MCC development in vivo. The ability to introduce patient variants to study their effects on disease progression makes Xenopus a powerful model to improve our understanding of the underlying disease mechanisms and explain the patient phenotype.
The excess insulin requirement in severe COVID‐19 compared to non‐COVID‐19 viral pneumonitis is related to the severity of respiratory failure and pre‐existing diabetes
Authors: Lockhart Sam M. , Griffiths Harry , Petrisor Bogdan , Usman Ammara , Calvo‐Latorre Julia , Heales Laura , Bansiya Vishakha , Mahroof Razeen , Conway Morris Andrew 
Published: February 2021

AbstractIntroductionSevere COVID‐19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS‐CoV‐2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID‐19 and non‐COVID‐19 viral pneumonitis.MethodsThis is a retrospective cohort study of patients with severe COVID‐19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non‐COVID‐19 viral pneumonitis patients was identified from routinely collected audit data.ResultsInsulin requirements were similar in patients with COVID‐19 and non‐COVID‐19 viral pneumonitis after adjustment for pre‐existing diabetes and severity of respiratory failure.ConclusionsIn this single‐centre study, we could not find evidence of a unique diabetogenic effect of COVID‐19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre‐existing metabolic disease.
Tracking mammals in a Lebanese protected area using environmental DNA‐based approach
Authors: Boukhdoud Liliane , Saliba Carole , Kahale Rhea , Bou Dagher Kharrat Magda 
Published: February 2021

AbstractMediterranean forest mammals are still poorly known, and few localities have been properly studied in the East Mediterranean Region (EMR). According to the IUCN Red List, many recorded species in this region are listed as threatened or endangered. Despite all threats, better management and more investments in species monitoring would surely improve the efficiency of biodiversity conservation projects to protect Mediterranean forest mammals. Protected reserves are of utmost importance for the conservation of native flora and fauna. Hereby, we provide a survey of mammals through a noninvasive technique based on environmental DNA extracted from scats. Samples were collected over 1 year covering all seasons from an important site for biodiversity conservation and scientific researches, the Horsh Ehden Nature Reserve. A total of 18 vertebrate species were recorded, many of them are endemic for the region and/or threatened especially in Lebanon. The use of noninvasive sampling method combined with genetic analysis of scats proved to be a powerful tool for species detection in a highly biodiverse protected area and can be easily replicated in any region around the world to rapidly assess species richness and therefore to apply direct conservation and management strategies toward species of interest.
Novel modulation technique to reduce acoustic noise and switching loss
Authors: Ayano Hideki , Kitada Masayoshi , Iguchi Yuki , Matsui Yoshihiro , Itoh Jun‐ichi 
Published: February 2021

AbstractThis paper proposes a novel modulation technique that reduces both motor acoustic noise and switching loss. The conventional discontinuous PWM method can reduce the switching loss to a greater extent compared to the conventional three‐phase modulation method; however, the acoustic noise of the motor increases. The proposed technique adjusts the zero‐sequence voltage given to the voltage references in such a way that the discontinuous part of the conventional discontinuous PWM method is changed smoothly. The switching loss with the proposed technique can be reduced to 58% of that with the conventional three‐phase modulation method. The experimental results show that the acoustic noise can be reduced to a greater extent with the proposed technique compared to that with the conventional discontinuous PWM method.
Self‐feeding assistive 7‐DOF robotic arm simulator using solving method of inverse kinematics
Authors: Shimabukuro Yuichi , Gushi Shotaro , Matayoshi Junji , Higa Hiroki 
Published: February 2021

AbstractIn order to help people with disabilities of the upper extremities drink and eat, a simulator for self‐feeding assistive robotic arm using solving method of inverse kinematics has been developed in this paper. Using inverse kinematics equations of 7 degrees of freedom (DOF) with an arm angle parameter, the robotic arm model was implemented in the simulator and its controller with mouse device was also designed. The arm angle parameter defined the angle between the arm plane and a reference plane was used to resolve the robotic arm redundancy. Three able‐bodied persons participated in simulation experiments. They manipulated the robotic arm model in a virtual space using mouse device. It was found from the simulation results they successfully performed the drinking and eating tasks in our simulator.
Charge/discharge control of wayside batteries via reinforcement learning for energy‐conservation in electrified railway systems
Authors: Yoshida Yasuhiro , Arai Sachiyo , Kobayashi Hiroyasu , Kondo Keiichiro 
Published: February 2021

AbstractThe effective utilization of regenerative power generated by trains has attracted the attention of engineers due to its promising potential in energy conservation for electrified railways. Charge control by wayside battery batteries is an effective method of utilizing this regenerative power. Wayside batteries requires saving energy by utilizing the minimum storage capacity of energy storage devices. However, because current control policies are rule‐based, based on human empirical knowledge, it is difficult to decide the rules appropriately considering the battery's state of charge. Therefore, in this paper, we introduce reinforcement learning with an actor‐critic algorithm to acquire an effective control policy, which had been previously difficult to derive as rules using experts’ knowledge. The proposed algorithm, which can autonomously learn the control policy, stabilizes the balance of power supply and demand. Through several computational simulations, we demonstrate that the proposed method exhibits a superior performance compared to existing ones.
Circulating multimarker approach to identify patients with preclinical left ventricular remodelling and/or diastolic dysfunction
Authors: Huttin Olivier , Kobayashi Masatake , Ferreira João Pedro , Coiro Stefano , Bozec Erwan , Selton‐Suty Christine , Filipetti Laura , Lamiral Zohra , Rossignol Patrick , Zannad Faiez , Girerd Nicolas 
Published: February 2021

AbstractAimsBiomarkers reflecting myocardial fibrosis and inflammation have been individually associated with left ventricular hypertrophy (LVH) and diastolic dysfunction (DD). However, the added value of a fibrosis‐inflammation multimarker approach in a populational setting is yet to be studied. We evaluated the value of a multimarker approach to detect LVH and DD in a large population‐based cohort.Methods and resultsIn a prespecified analysis (BioSe‐PreIC study) of the 4th visit of the STANISLAS cohort (1705 subjects, 47 ± 14 years, 47.4% men), we evaluated the ability of brain natriuretic peptide (BNP), Galectin‐3 (GAL3), N‐terminal propeptide of procollagen type III (P3NP), and soluble ST2 to predict LVH (LV mass > 116/100 g/m2 for men/women) and DD using discrimination (C‐index) and reclassification analysis (NRI).Participants with LVH and/or DD had significantly higher levels of BNP, GAL3, and ST2. Overall, the predictive value of clinical variables for LVH and/or DD was good (C‐index ranging from 0.76 to 0.82) and the addition of BNP, Gal3, P3NP, and ST2 moderately but significantly improved predictive value (delta C‐index = 0.03, P = 0.03 for LVH and 0.01, P = 0.01 for DD) and reclassification (NRI = 25.3, P = 0.02 for LVH and NRI = 32.7 for DD, P < 0.0001). Gal3, P3NP, and ST2 significantly improved predictive value (delta C‐index = 0.01, P = 0.01) and reclassification (NRI = 31.3, P < 0.0001) for DD of top of clinical variables and BNP.ConclusionsAs the measurement of Gal3, P3NP, and ST2 results in marginal (even if significant) increase in the prediction of DD/LVH on top of routine evaluation, their systematic use should not be promoted in unselected healthy individuals to screen for preclinical DD. Further research is needed to determine whether a more personalized medicine approach combing proteomic and clinical scoring can amplify the added value of biomarkers to identify preclinical DD.
Comparison of left ventricular longitudinal systolic function parameters in the prediction of adverse outcome in heart failure with preserved ejection fraction
Authors: Gozdzik Anna , Marwick Thomas H. , Przewlocka‐Kosmala Monika , Jankowska Ewa A. , Ponikowski Piotr , Kosmala Wojciech 
Published: February 2021

AbstractAimsSeveral different diagnostic parameters can be used to assess left ventricular (LV) longitudinal systolic function, but no studies comparing their predictive value have been conducted. We sought to compare the prognostic value of LV long‐axis function parameters at rest and exercise using the population with heart failure with preserved ejection fraction (HFpEF).Methods and resultsClinical and biochemical variables were collected at baseline in 201 patients with HFpEF. Echocardiography was performed at rest and immediately after exercise, with measurement of mitral annular plane systolic excursion, systolic tissue velocity (s′), global longitudinal strain (GLS), and global longitudinal strain rate (GLSR). Participants were followed for 48 (24–60) months for heart failure hospitalization and cardiovascular death. Seventy‐four patients (36.8%) met the study endpoint. Cox regression analysis revealed that after adjustment for Meta‐Analysis Global Group in Chronic Heart Failure risk score, brain natriuretic peptide (BNP), and peak VO2, heart failure hospitalization and cardiovascular death were significantly associated with GLS at rest [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.84–0.98; P = 0.016], GLS after exercise (HR 0.84; 95% CI 0.77–0.91; P < 0.001), and GLSR after exercise (HR 0.13; 95% CI 0.04–0.48; P = 0.002). The addition of each of the following: exercise GLS and GLSR and resting GLS to the base model including Meta‐Analysis Global Group in Chronic Heart Failure, BNP, and peak VO2 improved predictive power for the study endpoint [net reclassification improvement (NRI) = 49%, P < 0.001; NRI = 42%, P = 0.004; and NRI = 38%, P = 0.009, respectively]. Exercise GLS was the only longitudinal parameter significantly improving c‐statistics of the base model (0.68 vs. 0.73; P = 0.047).ConclusionsEchocardiographic parameters of LV longitudinal function are not equipotential in predicting adverse outcomes in HFpEF. LV deformation indices, especially assessed with exercise, show the highest predictive utility independent from and incremental to clinical data and BNP.
Can APIs that are Poorly Water‐ and Oil‐Soluble Benefit from Incorporation into SMEDDS? The Case of Dipyridamole
Authors: Rede Katarina , Bolko Seljak Katarina , Bogataj Marija , Gašperlin Mirjana 
Published: February 2021

AbstractThe aim of this study is to develop a self‐microemulsifying drug delivery system (SMEDDS) for the model active pharmaceutical ingredient (API) dipyridamole using exclusively excipients suitable for oral administration and nonvolatile cosolvents. Dipyridamole is a poorly water‐soluble and poorly oil‐soluble compound, which made it an atypical candidate for development of a lipid‐based drug delivery system (LBDDS). Four SMEDDS are successfully formulated, and dipyridamole has up to 1750‐fold higher solubility in the SMEDDS compared to water. Incorporation of 0.6–1% of dipyridamole into the SMEDDS does not considerably affect the droplet size, uniformity of droplet size distribution, and self‐emulsifying properties of the SMEDDS. The applicability of hard capsules for developing a final solid dosage form is tested by dissolution studies of dipyridamole from SMEDDS filled in gelatin and hydroxypropyl methylcellulose (HPMC) hard capsules. In addition, empty SMEDDS are filled into gelatin and HPMC hard capsules. They are stored for 16 weeks at ambient conditions and at 40 °C and 75% relative humidity. The dissolution properties and solubility of dipyridamole are considerably enhanced by incorporating dipyridamole into the SMEDDS; however, development of a final dosage form with hard capsules that are leak‐free for an extended period and at higher temperatures/humidity is still pending.Practical Applications: This study suggests that substances with low water solubility and low oil solubility can also benefit from incorporation into SMEDDS. Excipient selection needs to be considered carefully for such cases to maximize API incorporation and to ensure the self‐emulsifying properties of the formulation. In addition, only nonvolatile and orally acceptable excipients are used for preparation of SMEDDS, which is important when developing a formulation aimed for oral application. Hard capsules are a common approach for preparation of final dosage forms; however, obtaining leak‐free capsules can be challenging when liquid SMEDDS are used as filling. Storage for prolonged period and at higher temperatures/humidity is necessary for evaluation of liquid SMEDDS‐filled hard capsules.
The role of comparative victim beliefs in predicting support for hostile versus prosocial intergroup outcomes
Authors: Vollhardt Johanna Ray , Cohrs J. Christopher , Szabó Zsolt Péter , Winiewski Mikołaj , Twali Michelle S. , Hadjiandreou Eliana , McNeill Andrew 
Published: February 2021

AbstractCollective memories of historical ingroup victimization can be linked to prosocial or hostile intergroup outcomes. We hypothesize that such discrepant responses are predicted by different construals of the ingroup's victimization in relation to other groups (i.e., comparative victim beliefs). Using improved measures of inclusive and exclusive victim beliefs, with a global or regional reference group, multigroup structural equation modeling showed across four different groups (Armenian Americans [N = 265], Jewish Americans [N = 297], Hungarians [N = 301], Poles [N = 468]) that inclusive victim beliefs predict prosocial, conciliatory attitudes, while exclusive victim beliefs predict hostile attitudes towards historical perpetrator groups and (in the Polish and Hungarian samples) religious and ethnic outgroups targeted in the present. Moreover, comparative victim beliefs mediated effects of more general psychological orientations (ingroup superiority, universal orientation, perspective‐taking) on intergroup outcomes. These findings suggest the importance of considering distinct collective victim beliefs, and different contexts in research on collective victimhood.