bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional co‐activators YAP1–TAZ of Hippo signalling in doxorubicin‐induced cardiomyopathy
Authors: Berecz Tünde , Yiu Angela , Vittay Orsolya , Orsolits Barbara , Mioulane Maxime , dos Remedios Cristobal G. , Ketteler Robin , Merkely Bela , Apáti Ágota , Harding Sian E. , Hellen Nicola , Foldes Gabor 
Published: December 2021

AbstractAimsHippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem cell self‐renewal. Recently, the pathway has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, the functional role of this stress‐related and cell death‐related pathway in the human heart and cardiomyocytes is not known. In this study, we investigated the role of the transcriptional co‐activators of Hippo signalling, YAP and TAZ, in human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) in response to cardiotoxic agents and investigated the effects of modulating the pathway on cardiomyocyte function and survival.Methods and resultsRNA‐sequencing analysis of human heart samples with doxorubicin‐induced end‐stage heart failure and healthy controls showed that YAP and ERBB2 (HER2) as upstream regulators of differentially expressed genes correlated with doxorubicin treatment. Thus, we tested the effects of doxorubicin on hiPSC‐CMs in vitro. Using an automated high‐content screen of 96 clinically relevant antineoplastic and cardiotherapeutic drugs, we showed that doxorubicin induced the highest activation of YAP/TAZ nuclear translocation in both hiPSC‐CMs and control MCF7 breast cancer cells. The overexpression of YAP rescued doxorubicin‐induced cell loss in hiPSC‐CMs by inhibiting apoptosis and inducing proliferation. In contrast, silencing of YAP and TAZ by siRNAs resulted in elevated mitochondrial membrane potential loss in response to doxorubicin. hiPSC‐CM calcium transients did not change in response to YAP/TAZ silencing.ConclusionsOur results suggest that Hippo signalling is involved in clinical anthracycline‐induced cardiomyopathy. Modelling with hiPSC‐CMs in vitro showed similar responses to doxorubicin as adult cardiomyocytes and revealed a potential cardioprotective effect of YAP in doxorubicin‐induced cardiotoxicity.
High selenium levels associate with reduced risk of mortality and new‐onset heart failure: data from PREVEND
Authors: Al‐Mubarak Ali A. , Grote Beverborg Niels , Suthahar Navin , Gansevoort Ron T. , Bakker Stephan J.L. , Touw Daan J. , de Boer Rudolf A. , van der Meer Peter , Bomer Nils 
Published: December 2021

AimTo elucidate the relationship between serum selenium levels and the risk of mortality and new‐onset heart failure (HF) in the general adult population.Methods and resultsSelenium was measured in a Dutch cohort and a retrospective analysis of prospectively assessed data was performed. Main outcome measures were all‐cause mortality and incidence of new‐onset HF separately, and combined as a composite endpoint. Serum selenium was measured in 5973 subjects and mean selenium concentration was 84.6 (±19.5) µg/L. Mean age was 53.6 (±12.1) years and 3103 subjects (52%) were female. Median follow‐up was 8.4 years. Selenium levels associated positively with female sex, higher total cholesterol and glucose concentrations, and associated negatively with incidence of anaemia, iron deficiency, current smoking, increased C‐reactive protein levels, and higher body mass index. Univariate analysis on all subjects showed no association of continuous selenium concentrations, per 10 µg/L increase, with the composite endpoint (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.87–1.06, p = 0.407). However, significant interaction with smoking status was observed. In non‐smoking subjects (n = 4288), continuous selenium concentrations were independently associated with reduced mortality risk (HR 0.87, 95% CI 0.79–0.96, p = 0.005), lower risk of new‐onset HF (HR 0.82, 95% CI 0.69–0.96, p = 0.017), as well as reduced risk of the composite endpoint (HR 0.86, 95% CI 0.79–0.94, p = 0.001). In smoking subjects, no associations were found.ConclusionSerum selenium was independently associated with multiple indicators of the metabolic syndrome. In addition, high selenium levels were independently associated with reduced mortality and new‐onset HF in non‐smokers. Well‐powered interventional studies are necessary to evaluate the potential benefit of repleting selenium, especially in non‐smoking subjects.
Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C‐type lectin receptor Langerin
Authors: Bellmann Lydia , Strandt Helen , Zelle‐Rieser Claudia , Ortner Daniela , Tripp Christoph H. , Schmid Sandra , Rühl Julia , Cappellano Giuseppe , Schaffenrath Sandra , Prokopi Anastasia , Spoeck Sarah , Seretis Athanasios , Del Frari Barbara , Sigl Stephan , Krapf Johanna , Heufler Christine , Keler Tibor , Münz Christian , Romani Nikolaus , Stoitzner Patrizia 
Published: December 2021

AbstractHuman skin is a preferred vaccination site as it harbors multiple dendritic cell (DC) subsets, which display distinct C‐type lectin receptors (CLR) that recognize pathogens. Antigens can be delivered to CLR by antibodies or ligands to boost antigen‐specific immune responses. This concept has been established in mouse models but detailed insights into the functional consequences of antigen delivery to human skin DC in situ are sparse. In this study, we cloned and produced an anti‐human Langerin antibody conjugated to the EBV nuclear antigen 1 (EBNA1). We confirmed specific binding of anti‐Langerin‐EBNA1 to Langerhans cells (LC). This novel LC‐based vaccine was then compared to an existing anti‐DEC‐205‐EBNA1 fusion protein by loading LC in epidermal cell suspensions before coculturing them with autologous T cells. After restimulation with EBNA1‐peptides, we detected elevated levels of IFN‐γ‐ and TNF‐α‐positive CD4+ T cells with both vaccines. When we injected the fusion proteins intradermally into human skin explants, emigrated skin DC targeted via DEC‐205‐induced cytokine production by T cells, whereas the Langerin‐based vaccine failed to do so. In summary, we demonstrate that antibody‐targeting approaches via the skin are promising vaccination strategies, however, further optimizations of vaccines are required to induce potent immune responses.
PAHs Containing both Heptagon and Pentagon: Corannulene Extension by [5+2] Annulation
Authors: Schnitzlein Matthias , Mützel Carina , Shoyama Kazutaka , Farrell Jeffrey M. , Würthner Frank 
Published: December 2021

AbstractUtilizing Pd‐catalyzed [5+2] annulation a series of heptagon‐extended corannulenes could be synthesized from a borinic acid precursor furnished by C−H borylation strategy. Single‐crystal X‐ray analysis revealed the presence of two conformational enantiomers crystallizing in a racemic mixture. Through their embedded five‐ and seven‐membered rings these polycyclic aromatic hydrocarbons (PAHs) exhibit both negative and positive curvature and UV/Vis/NIR absorption spectroscopy as well as cyclic voltammetry experiments provided insights into the influence of larger flanking aromatic systems and electron‐donating substituents encompassing the heptagonal ring. Through [5+2] annulation of acenaphthylene an azulene‐containing PAH with intriguing optoelectronical properties including a very small bandgap and absorption over the whole visible spectrum could be obtained. Theoretical calculations were employed to elucidate the long‐wavelength absorption and aromaticity.
Oligonucleotide Conjugation by Tyrosine‐Click Reaction
Authors: Meyer Albert , Baraguey Carine , Vasseur Jean‐Jacques , Morvan François 
Published: December 2021

AbstractN,O‐Diacetyl tyrosine and 3‐(4‐hydroxy‐phenyl)‐propanoic acid were converted into phosphoramidite derivatives and introduced to the 5′‐end of oligonucleotides. The resulting oligonucleotides exhibiting a 4‐hydroxyphenyl alkyl group were conjugated with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione as a model of a Y‐click reaction. The reaction is fast (<1 h) and efficient (>90 %). A partial side reaction occurred at the C8 position of deoxyguanosine in single‐stranded oligonucleotides. This side reaction does not take place on the G quadruplex and double‐stranded oligonucleotides and when N2 position of guanine is protected. This Y‐click reaction could be applied to 1,2,4‐triazoline‐3,5‐dione derivatives displaying a fluorescent dye, a carbohydrate or orthogonal functions (alkyne, azide, ketone or maleimide) for the labelling of oligonucleotides.
Collective victimhood and support for joint political decision‐making in conflict regions: The role of shared territorial ownership perceptions
Authors: Storz Nora , Bilali Rezarta , Martinović Borja , Maloku Edona , Rosler Nimrod , Žeželj Iris 
Published: December 2021

AbstractIn territorial interethnic conflicts people often claim exclusive land ownership for their ingroup. However, they can also view the ingroup and outgroup as entitled to the land. It is unknown what explains such shared ownership perceptions and how these in turn inform opinions about conflict resolution. We focused on different types of collective victimhood as precursors of shared ownership perceptions, and on joint decision‐making as a political outcome. In the context of the Israeli–Palestinian and Kosovo disputes, using national samples of Jewish Israelis (N = 609, Study 1) and Albanians and Serbs (N = 995, Study 2), we found that inclusive victimhood was related to higher, and competitive victimhood to lower, shared ownership perceptions. Shared ownership was, in turn, related to more support for joint decision‐making. Our findings highlight the importance of collective victimhood in explaining shared ownership perceptions, which consequently inform opinions about the political route to conflict resolution.
Toward eco‐friendly and stable halide perovskite‐inspired materials for light‐emitting devices applications by dimension classification: Recent advances and opportunities
Authors: Wang Yue , Zhang Fei , Ma Jingli , Ma Zhuangzhuang , Chen Xu , Wu Di , Li Xinjian , Shi Zhifeng , Shan Chongxin 
Published: December 2021

AbstractResearch on lead‐halide perovskites for photovoltaic and optoelectronic applications represents a rapidly developing field of optoelectronics on account of their remarkable optoelectronic properties, including large absorption coefficient, low‐temperature solution processability, tunable bandgap, high‐carrier mobility, and so on. Unfortunately, the toxicity of metal Pb and intrinsic instability of lead‐halide perovskites are still big obstacles for their practical applications and future commercial development. Therefore, various lead‐free eco‐friendly perovskites and their derivatives have been alternatively explored to overcome the above hurdles. In this review, the preparation methods, structures, optical characteristics, and stability of lead‐free metal halide perovskites are summarized according to different dimensions at molecular level. Furthermore, we emphatically introduce the optoelectronic properties of low‐dimensional lead‐free halides with broadband emission originated from the self‐trapped excitons. Then, we give a brief description of preliminary exploration results and significant achievements of optically excited white light‐emitting devices (WLEDs) and electrically excited multi‐color LEDs. Finally, this review was finished with a critical perspective into the potential challenging issues of this rapidly evolving fields.image
Femtosecond laser‐produced optical absorbers for solar‐thermal energy harvesting
Authors: Singh Subhash C. , Guo Chunlei 
Published: December 2021

AbstractOptical absorbers are a key component in all solar‐thermal energy technologies. Cermet‐based solar absorbers are commonly used in solar‐thermal applications. However, due to their multilayered structures, these absorbers have limited thermal conductivity and mechanical stability at the interfaces. Femtosecond laser processing is a single‐step, environmentally friendly, and monolithic approach that can directly transform a metal surface to a solar absorber through surface patterning without adding additional weight, hazard, or complexity. In this review, we will focus on femtosecond‐laser induced broadband and selective solar absorbers and their utilizations in solar thermoelectric generators and solar‐thermal water purification. We will discuss the laser surface patterning and the procedure to control the size, distribution, and composition of the surface structures that are responsible for optical absorbance/emittance. Several multifunctional solar absorber surfaces produced by femtosecond‐laser processing and their possible energy applications are also discussed.image
Molecule‐Specific Uncertainty Quantification in Quantum Chemical Studies
Authors: Reiher Markus 
Published: December 2021

AbstractSolving the electronic Schrödinger equation for changing nuclear coordinates provides access to the Born‐Oppenheimer potential energy surface. This surface is the key starting point for almost all theoretical studies of chemical processes in electronic ground and excited states (including molecular structure prediction, reaction mechanism elucidation, molecular property calculations, quantum and molecular dynamics). Electronic structure models aim at a sufficiently accurate approximation of this surface. They have therefore become a cornerstone of theoretical and computational chemistry, molecular physics, and materials science. In this work, we elaborate on general features of approximate electronic structure models such as accuracy, efficiency, and general applicability in order to arrive at a perspective for future developments, of which a vanguard has already arrived. Our quintessential proposition is that meaningful quantum mechanical predictions for chemical phenomena require system‐specific uncertainty information for each and every electronic structure calculation, if objective conclusions shall be drawn with confidence.
Risk Factors and Consequences of Lower Extremity Fracture Nonunions in Veterans With Spinal Cord Injury
Authors: Sinnott Bridget , Ray Cara , Weaver Frances , Gonzalez Beverly , Chu Elizabeth , Premji Sarah , Raiford Mattie , Elam Rachel , Miskevics Scott , Parada Stephen , Carbone Laura 
Published: December 2021

ABSTRACTWe used Veterans Health Administration (VHA) national administrative data files to identify a cohort (fiscal years 2005–2014) of veterans with spinal cord injuries and disorders (SCID) to determine risk factors for and consequences of lower extremity fracture nonunions. Odds ratios (OR) for fracture nonunion were computed using multivariable‐adjusted logistic regression models. We identified three risk factors for nonunion: (i) older age (OR = 2.29; 95% confidence interval [CI] 1.21–4.33), (ii) longer duration of SCID (OR = 1.02; 95% CI 1.00–1.04), and (iii) fracture site (distal femur), with OR (comparison distal femur) including distal tibia/fibula (OR = 0.14; 95% CI 0.09–0.24), proximal tibia/fibula (OR = 0.19; 95% CI 0.09–0.38), proximal femur (OR = 0.10; 95% CI 0.04–0.21), and hip (OR = 0.13; 95% CI 0.07–0.26). Nonunions resulted in multiple complications, with upwards of 1/3 developing a pressure injury, 13% osteomyelitis, and almost 25% requiring a subsequent amputation. Our data have identified a high‐risk population for fracture nonunion of older veterans with a long duration of SCID who sustain a distal femur fracture. In view of the serious complications of these nonunions, targeted interventions in these high‐risk individuals who have any signs of delayed union should be considered. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Inorganic Reinforced Poly(ionic liquid) Microcapsules: Confined Cooling‐Assisted Phase Separation Self‐Assembly and Enhanced Electroresponsive Properties
Authors: Lei Qi , He Fang , Zhao Xiaopeng , Yin Jianbo 
Published: December 2021

AbstractA simple preparation of inorganic reinforced poly(ionic liquid) (PIL) microcapsules by combining dispersion polymerization and confined cooling‐assisted phase separation self‐assembly is reported. Silane coupling agent‐modified PIL microbeads are first prepared by dispersion polymerization. Then, the microbeads are dissolved in a theta solvent composed of good solvent and non‐solvent to form hollow SiOx microcapsules at a relatively high temperature. Finally, the solution is cooled to induce the nucleation and growth of dissolved PIL chains on the inner and outer surface of hollow SiOx microcapsules to form inorganic reinforced microcapsules with asymmetric PIL/SiOx/PIL sandwich‐like shell. The morphology of microcapsules can be controlled by adjusting PIL concentration and cooling rate. The inorganic reinforced microcapsules show enhanced suspended stability and electroresponsive characteristic when used as the dispersed phase of smart suspensions.
Terpene Lactucopicrin Limits Macrophage Foam Cell Formation by a Reduction of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Lipid Rafts
Authors: Li Qing , Liu Xiuping , Zhang Xu , Du Yushi , Chen Guanyu , Xiang Panyin , Ling Wenhua , Wang Dongliang 
Published: December 2021

ScopeSustained inflammation promotes macrophage foam cell formation by promoting cholesterol influx and impairing cholesterol efflux. Terpene lactucopicrin, affluent in vegetables of the Asteraceae family (e.g., chicory, curly escarole, and lettuce) can inhibit atherogenesis in mice. However, it remains unknown whether and how lactucopicrin regulates macrophage foam cell formation.Methods and ResultsLactucopicrin at physiologically reachable concentrations inhibits oxidized low‐density lipoprotein (oxLDL)‐induced foam cell formation in inflammatory mouse bone marrow derived macrophages established by 50 pg mL–1of LPS, reachable level in patients with metabolic endotoxemia. This effect is not due to modulation of cholesterol efflux, but reliant on a reduction in lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1)‐mediated cholesterol influx. Mechanistically, lactucopicrin does not affect LOX‐1 expression, cellular oxidative stress, and exocytosis, known mechanisms regulating LOX‐1 function in cholesterol influx. Strikingly, lactucopicrin selectively decreases LOX‐1 content in lipid rafts, an effect responsible for the lactucopicrin effect on cholesterol influx. Moreover, ApoE–/–mice fed a high fat diet supplemented with lactucopicrin for 12 weeks display fewer macrophage foam cells within atherosclerotic plaques relative to the control mice.ConclusionLactucopicrin limits macrophage foam cell formation through a reduction of LOX‐1 distribution in lipid rafts, thus contributing to its atheroprotective effect.
COVID‐19 and mental health among at‐risk university students: A prospective study into risk and protective factors
Authors: Koelen Jurrijn A. , Mansueto Alessandra C. , Finnemann Adam , de Koning Lisa , van der Heijde Claudia M. , Vonk Peter , Wolters Nine E. , Klein Anke , Epskamp Sacha , Wiers Reinout W. 
Published: December 2021

AbstractObjectiveThe COVID‐19 pandemic has confronted young adults with an unprecedented mental health challenge. Yet, prospective studies examining protective factors are limited.MethodsIn the present study, we focused on changes in mental health in a large sample (N = 685) of at‐risk university students, which were measured before and during the pandemic. Network modeling was applied to 20 measured variables to explore intercorrelations between mental health factors, and to identify risk and protective factors. Latent change score modeling was used on a subset of variables.ResultsThe main findings indicate that (1) mental health problems increased at group level, especially depression‐anxiety and loneliness; (2) emotional support during the COVID pandemic was associated with smaller increases in loneliness and depression‐anxiety; (3) COVID‐related stress predicted increases in depression‐anxiety; (4) loneliness acted as a bridge construct between emotional support and changes in mental health.ConclusionTo mitigate the impact of the COVID‐19 pandemic on the mental health of young adults, is it recommended to focus on interventions that strengthen internal resources (stress‐regulating abilities) and reduce loneliness.
MR spectroscopy frequency and phase correction using convolutional neural networks
Authors: Ma David J. , Le Hortense A‐M. , Ye Yuming , Laine Andrew F. , Lieberman Jeffery A. , Rothman Douglas L. , Small Scott A. , Guo Jia 
Published: December 2021

PurposeTo introduce a novel convolutional neural network (CNN)‐based approach for frequency‐and‐phase correction (FPC) of MR spectroscopy (MRS) spectra to achieve fast and accurate FPC of single‐voxel MEGA‐PRESS MRS data.MethodsTwo neural networks (one for frequency and one for phase) were trained and validated using published simulated and in vivo MEGA‐PRESS MRS dataset with wide‐range artificial frequency and phase offsets applied. The CNN‐based approach was subsequently tested and compared to the current deep learning solution: multilayer perceptrons (MLP). Furthermore, random noise was added to the original simulated dataset to further investigate the model performance at varied signal‐to‐noise ratio (SNR) levels (i.e., 10, 5, and 2.5). Additional frequency and phase offsets (i.e., small, moderate, large) were also applied to the in vivo dataset, and the CNN model was compared to the conventional approach SR and model‐based SR implementation (mSR).ResultsThe CNN model is more robust to noise compared to the MLP‐based approach due to having smaller mean absolute errors in both frequency (0.01 ± 0.01 Hz at SNR = 10 and 0.01 ± 0.02 Hz at SNR = 2.5) and phase (0.12 ± 0.09° at SNR = 10 and −0.07 ± 0.44° at SNR = 2.5) offset prediction. Furthermore, better performance was demonstrated for FPC when compared to the MLP‐based approach, and SR when applied to the in vivo dataset for both with and without additional offsets.ConclusionA CNN‐based approach provides a solution to the automated preprocessing of MRS data, and the experimental results demonstrate the quantitatively improved spectra quality compared to the state‐of‐the‐art approach.
Association between emergency department length of stay and patient outcomes: A systematic review
Authors: Burgess Luke , Ray‐Barruel Gillian , Kynoch Kathryn 
Published: December 2021

AbstractIn this review, we investigate associations between time spent in the emergency department (ED) and patient reported outcomes. ED staff provide initial assessment, treatment and referral to patients presenting with an acute status to the hospital 24 h a day. ED length of stay, including ED boarding, and treatment received in the ED may affect patient outcomes. In this review we considered published studies that explored the association of ED length of stay of individuals of any age with their subsequent outcomes, including mortality and inpatient length of stay (IPLOS). Joanna Briggs Institute methods for systematic reviews of association were followed. Search strategies were developed to identify studies published in English since 2000 for inclusion. Two reviewers assessed the studies for inclusion and methodological quality and extracted data independently. In total, 34 studies were included in the review, including one case‐control, one analytical cross‐sectional, and 32 retrospective cohort studies, with a total sample size of 2,308,840 patients. Overall, there were variable associations of time spent in the ED and mortality, IPLOS, time‐to‐treatment and adverse events. However, findings indicated that older people are at risk for longer ED stays. They may also experience higher mortality. Specific focus should be placed upon elderly people in the ED, to reduce their exposure to the ED environment where possible and to implement focused initiatives that address their specific and complex treatment needs. We conclude that the diversity of individual settings and health systems will require locally defined and relevant solutions to locally identified issues.