bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental evidence for proarrhythmic effects of nonsteroidal anti‐inflammatory drugs in a sensitive whole‐heart model
Authors: Wolfes Julian , Ellermann Christian , Bäumer Svenja , Fehr Michael , Willy Kevin , Wegner Felix , Leitz Patrick R. , Eckardt Lars , Frommeyer Gerrit 
Published: October 2021

AbstractBackgroundPrevious studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti‐inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia.Methods and resultsThirty‐eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 μM), indomethacin (Group 2, n = 13; 10 and 20 μM) and diclofenac (Group 3, n = 13; 10 and 20 μM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations.ConclusionThe perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole‐heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.
Intestinal pathophysiological abnormalities in steady state and after vaso‐occlusive crisis in murine sickle cell disease
Authors: Poplawska Maria , Dutta Dibyendu , Jayaram Manjunath , Salifu Moro , Chong Ngee S. , Lim Seah H. 
Published: October 2021

SummaryWe showed in the present study that, not unlike in adult patients with sickle cell disease (SCD), Townes mice exhibit increases in serum intestinal fatty acid binding proteins and lipopolysaccharides (LPS), together with a breach in the intestinal barrier. These abnormalities increased rapidly after the induction of vaso‐occlusive crisis (VOC). We also confirmed higher intestinal microbial density in SCD. These findings support the concept that SCD and/or its complications, and not hospitalisation or medications, are responsible for the intestinal pathophysiological changes. The present results provide the basis for use of Townes mice to further elucidate the mechanistic relationship between intestinal pathophysiology and VOC.
Role of NaV1.7 in action potential conduction along human bronchial vagal afferent C‐fibres
Authors: Kollarik Marian , Ru Fei , Pavelkova Nikoleta , Mulcahy John , Hunter John , Undem Bradley J. 
Published: October 2021

Background and PurposeThe purpose of this study was to determine the role of NaV1.7 in action potential conduction in C‐fibres in the bronchial branches of the human vagus nerve.Experimental ApproachBronchial branches of the vagus nerve were dissected from human donor tissue. The C‐wave of the electrically evoked compound action potential was quantified in the absence and presence of increasing concentrations of the selective NaV1.7 blocking drugs, PF‐05089771 and ST‐2262, as well as the NaV1.1, 1.2, and 1.3 blocking drug ICA121‐431. The efficacy and potency of these inhibitors were compared to the standard NaV1 blocker, tetrodotoxin. We then compared the relative potencies of the NaV1 blockers in inhibiting the C‐wave of the compound action potential, with their ability to inhibit parasympathetic cholinergic contraction of human isolated bronchi, a response previously shown to be strictly dependent on NaV1.7 channels.Key ResultsThe selective NaV1.7 blockers inhibited the C‐wave of the compound action potential with potencies similar to that observed in the NaV1.7 bronchial contractions assay. Using rt‐PCR, we noted that NaV1.7 mRNA was strongly expressed and transported down the vagus nerve bundles.Conclusions and ImplicationsNaV1.7 blockers can prevent action potential conduction in the majority of vagal C‐fibres arising from human bronchi. Blockers of NaV1.7 channels may therefore have value in inhibiting the responses to excessive airway C‐fibre activation in inflammatory airway disease, responses that include coughing as well as reflex bronchoconstriction and secretions.
Young children’s agency with digital technologies
Authors: Nolan Andrea , Edwards Susan , Salamon Andi , Straker Leon , Grieshaber Susan , Skouteris Helen , Henderson Michael , Highfield Kate , Bartlett Jacinta 
Published: October 2021

AbstractThis paper examines the evidence of children's agency in research about infants, toddlers and technologies. It finds that an implicit reliance on technological determinism as a theoretical perspective for positioning technologies relative to young children's development tends to shape research in terms of understanding the impact of technologies on young children. Drawing on critical constructivism as a philosophical stance on technologies, this paper argues that children's agency with technologies may be further investigated in terms of practice architectures to better understand the social mediation of infant and toddler interactions and engagements with technologies.
Preschoolers’ relevance inferences in linguistic and non‐linguistic contexts
Authors: Sullivan Jessica , Alvarez Joseph , Goldstein Blair 
Published: October 2021

AbstractUnderstanding symbols requires going beyond what they literally are, and figuring out what they're intended to communicate. For example, a drawing of a bird (or the word bird) could refer to a particular bird, a species, etc… The interpreter must decide between these intended meanings. We ask how children go beyond the literal meanings of communicative acts (i.e., compute pragmatic inferences), and whether these inferences are domain‐general. We tested 443 US 2‐ to 6‐year‐olds’ inferences about the referential interpretation of ambiguous symbols. We manipulated the domain (e.g., word or a drawing) and task (interpret vs. create the communicative act). Children robustly identified the referents of ambiguous symbols and chose from among alternatives during linguistic and non‐linguistic communication tasks. There were no effects of age or domain on performance. These data provide some of the earliest evidence of children's computations of pragmatic inferences, and provide exciting evidence that pragmatic inferences may extend beyond the domain of language.
Fiber‐specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis
Authors: Ogura Aya , Kawabata Kazuya , Watanabe Hirohisa , Choy Shao Wei , Bagarinao Epifanio , Kato Toshiyasu , Imai Kazunori , Masuda Michihito , Ohdake Reiko , Hara Kazuhiro , Nakamura Ryoichi , Atsuta Naoki , Nakamura Tomohiko , Katsuno Masahisa , Sobue Gen 
Published: October 2021

AbstractBackground and purposeTo clarify the relationship between fiber‐specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel‐based analysis (FBA), a novel framework for diffusion‐weighted imaging analysis.MethodsWe enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age‐ and sex‐matched healthy controls (HCs), in this study and conducted whole‐brain FBA and voxel‐based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross‐section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract‐of‐interest analysis to extract FD values across the significant regions in the whole‐brain analysis. Then, we evaluated the associations between FD values and clinical variables.ResultsThe bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p < 0.05, familywise error‐corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel‐based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho = −0.530, p < 0.001; central motor conduction time [CMCT] in the upper limb: rho = −0.474, p = 0.008; disease duration: rho = −0.383, p = 0.007; ALS Functional Rating Scale‐Revised: rho = 0.340, p = 0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs.ConclusionsOur findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments.
Performing nationalism: The United Nations Human Rights Council (UNHRC) and Sri Lankan Tamil diasporic politics in Switzerland
Authors: Thurairajah Tanuja 
Published: October 2021

AbstractThe history of post‐war Sri Lanka has seen an escalation of nationalisms that constantly collide. Post‐2009, with the end of the war, the reproduction of narratives around nationalisms has become intense, with home‐grown protests for accountability of minority injustices continuing to sustain its fervour over time. Within the context of Switzerland these events in Sri Lanka are invariably aligned with diasporic engagement. Dominant spaces such as the United Nations (UN) in Geneva, Switzerland become transnational sites for the performance of long‐distance nationalism by Tamil diaspora groups, raising questions around legitimacy and claims‐making. This paper presents empirical insights as to how long‐distance Tamil nationalism is manifested as political engagement, by groups, and/ or individuals, in formal and informal transnational sites within the socio‐political landscape of Switzerland. It argues that modes of political engagement are manifested through rituals of performance and performativity such as scripting and iteration of claims‐making processes that enable legitimacy in transnational sites of lobby and protest within the UN arena in Geneva during the Human Rights Council (HRC) sessions. The paper situates its analysis within a shift in post‐war Tamil diaspora claims‐making narratives from a separatist stance to that of victimhood and human rights producing narratives that present the Tamil diaspora as a singular actor albeit with complex heterogeneity.
Cation exchange synthesis of porous Cd1‐xZnxS twinned nanosheets for visible light highly active H2 evolution
Authors: Wang Jing , Li Jiajia , Xiao Lu , Kurbanjan Dilnur , Nie Hong , Du Hong 
Published: October 2021

AbstractEfficient charge separation is critical for the enhancement of photocatalytic activity for hydrogen generation. The porous Cd1‐xZnxS nanosheets with twinned phase junctions were synthesized by the cation‐exchange approach of inorganic‐organic hybrid ZnS‐diethylenetriamine nanoflakes with cadmium ions. With the synergy of the phase junctions induced by nano twins and porous structure, the hydrogen evolution average rate over the optimal sample Cd0.5Zn0.5S photocatalyst reaches 14.44 mmol h−1 g−1 without noble metal loading under visible light irradiation, corresponding to apparent quantum efficiency of 37.3% at 420 nm and solar‐to‐hydrogen energy conversion efficiency of 3.46%. On the one hand, twin‐induced phase junctions can improve the separation efficiency of photoelectron‐hole pairs, on the other hand, the large specific surface area ascribed to the porous nanosheet can effectively improve the light absorption capacity of photocatalysis, and provide more surface active sites. This study could provide a facile approach to design and fabricate advanced materials with porous twinned phase junctions for photocatalytic applications and optoelectronic devices.
Identification of pyroptosis‐related lncRNAs for constructing a prognostic model and their correlation with immune infiltration in breast cancer
Authors: Lv Wenchang , Tan Yufang , Zhao Chongru , Wang Yichen , Wu Min , Wu Yiping , Ren Yuping , Zhang Qi 
Published: October 2021

AbstractThe inflammasome‐dependent cell death, which is denoted as pyroptosis, might be abnormally regulated during oncogenesis and tumour progression. Long non‐coding RNAs (LncRNAs) are pivotal orchestrators in breast cancer (BC), which have the potential to be a biomarker for BC diagnosis and therapy. The present study aims to explore the correlation between pyroptosis‐related lncRNAs and BC prognosis. In this study, a profile of 8 differentially expressed lncRNAs was screened in the TCGA database and used to construct a prognostic model. The BC patients were divided into high‐ and low‐risk groups dependent on the median cutoff of the risk score in the model. Interestingly, the risk model significantly distinguished the clinical characteristics of BC patients between high‐ and low‐risk groups. Then, the risk score of the model was identified to be an excellent independent prognostic factor. Notably, the GO, KEGG, GSEA and ssGSEA analyses revealed the different immune statuses between the high‐ and low‐risk groups. Particularly, the 8 lncRNAs expressed differentially in BC tissues between two risk subgroups in vitro validation. Collectively, this constructed well‐validated model is of high effectiveness to predict the prognosis of BC, which will provide novel means that is applicable for BC prognosis recognition.
Comparative transcriptomic analysis of THP‐1‐derived macrophages infected with Mycobacterium tuberculosis H37Rv, H37Ra and BCG
Authors: Pu Wenyuan , Zhao Chen , Wazir Junaid , Su Zhonglan , Niu Mengyuan , Song Shiyu , Wei Lulu , Li Li , Zhang Xia , Shi Xudong , Wang Hongwei 
Published: October 2021

AbstractTuberculosis (TB) remains a worldwide healthcare concern, and the exploration of the host‐pathogen interaction is essential to develop therapeutic modalities and strategies to control Mycobacterium tuberculosis (M.tb). In this study, RNA sequencing (transcriptome sequencing) was employed to investigate the global transcriptome changes in the macrophages during the different strains of M.tb infection. THP‐1 cells derived from macrophages were exposed to the virulent M.tb strain H37Rv (Rv) or the avirulent M.tb strain H37Ra (Ra), and the M.tb BCG vaccine strain was used as a control. The cDNA libraries were prepared from M.tb‐infected macrophages and then sequenced. To assess the transcriptional differences between the expressed genes, the bioinformatics analysis was performed using a standard pipeline of quality control, reference mapping, differential expression analysis, protein‐protein interaction (PPI) networks, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Q‐PCR and Western blot assays were also performed to validate the data. Our findings indicated that, when compared to BCG or M.tb H37Ra infection, the transcriptome analysis identified 66 differentially expressed genes in the M.tb H37Rv‐infected macrophages, out of which 36 genes were up‐regulated, and 30 genes were down‐regulated. The up‐regulated genes were associated with immune response regulation, chemokine secretion, and leucocyte chemotaxis. In contrast, the down‐regulated genes were associated with amino acid biosynthetic and energy metabolism, connective tissue development and extracellular matrix organization. The Q‐PCR and Western blot assays confirmed increased expression of pro‐inflammatory factors, altered energy metabolic processes, enhanced activation of pro‐inflammatory signalling pathways and increased pyroptosis in H37Rv‐infected macrophage. Overall, our RNA sequencing‐based transcriptome study successfully identified a comprehensive, in‐depth gene expression/regulation profile in M.tb‐infected macrophages. The results demonstrated that virulent M.tb strain H37Rv infection triggers a more severe inflammatory immune response associated with increased tissue damage, which helps in understanding the host‐pathogen interaction dynamics and pathogenesis features in different strains of M.tb infection.
Impaired reproductive fitness despite high fecundity in European eel (Anguilla anguilla L.) from a Baltic Sea drainage area
Authors: Reismann Theresa , Frankowski Jens 
Published: October 2021

AbstractThe reproductive fitness of female European eels (Anguilla anguilla L.) from the Warnow River, Germany, Baltic Sea region, was evaluated by estimating fecundity and applying a spawning model. Individual fecundity ranged from 1,440,000 to 7,455,000 oocytes and mean relative fecundity equalled 5,956,015 oocytes kg−1. Modelling suggests that 43% of eels hold insufficient energy storages or are within 10% of complete depletion. The fraction of eels with insufficient energy supply increases from 19% to 35% if the effect of parasitic infection is considered.
Differential hyperpolarization to substance P and calcitonin gene‐related peptide in smooth muscle versus endothelium of mouse mesenteric artery
Authors: Norton Charles E. , Boerman Erika M. , Segal Steven S. 
Published: October 2021

AbstractObjectiveWe sought to define how sensory neurotransmitters substance P and calcitonin gene‐related peptide (CGRP) affect membrane potential of vascular smooth muscle and endothelium.MethodsMicroelectrodes recorded membrane potential of smooth muscle from pressurized mouse mesenteric arteries (diameter, ~150 µm) and in endothelial tubes.ResultsResting potential was similar (~ −45 mV) for each cell layer. Substance P hyperpolarized smooth muscle and endothelium ~ −15 mV; smooth muscle hyperpolarization was abolished by endothelial disruption or NO synthase inhibition. Blocking KCa channels (apamin + charybdotoxin) attenuated hyperpolarization in both cell types. CGRP hyperpolarized endothelium and smooth muscle ~ −30 mV; smooth muscle hyperpolarization was independent of endothelium. Blocking KCa channels prevented hyperpolarization to CGRP in endothelium but not smooth muscle. Inhibiting KATP channels with glibenclamide or genetic deletion of KIR6.1 attenuated hyperpolarization in smooth muscle but not endothelium. Pinacidil (KATP channel agonist) hyperpolarized smooth muscle more than endothelium (~ −35 vs. ~ −20 mV).ConclusionsCalcitonin gene‐related peptide elicits greater hyperpolarization than substance P. Substance P hyperpolarizes both cell layers through KCa channels and involves endothelium‐derived NO in smooth muscle. Endothelial hyperpolarization to CGRP requires KCa channels, while KATP channels mediate hyperpolarization in smooth muscle. Differential K+ channel activation in smooth muscle and endothelium through sensory neurotransmission may selectively tune mesenteric blood flow.
Phytoglobin‐NO cycle and AOX pathway play a role in anaerobic germination and growth of deepwater rice
Authors: Kumari Aprajita , Singh Pooja , Kaladhar Vemula Chandra , Manbir  , Paul Debarati , Pathak Pradeep Kumar , Gupta Kapuganti Jagadis 
Published: October 2021

AbstractAn important and interesting feature of rice is that it can germinate under anoxic conditions. Though several biochemical adaptive mechanisms play an important role in the anaerobic germination of rice but the role of phytoglobin‐nitric oxide cycle and alternative oxidase pathway is not known, therefore in this study we investigated the role of these pathways in anaerobic germination. Under anoxic conditions, deepwater rice germinated much higher and rapidly than aerobic condition and the anaerobic germination and growth were much higher in the presence of nitrite. The addition of nitrite stimulated NR activity and NO production. Important components of phytoglobin‐NO cycle such as methaemoglobin reductase activity, expression of Phytoglobin1, NIA1 were elevated under anaerobic conditions in the presence of nitrite. The operation of phytoglobin‐NO cycle also enhanced anaerobic ATP generation, LDH, ADH activities and in parallel ethylene levels were also enhanced. Interestingly nitrite suppressed the ROS production and lipid peroxidation. The reduction of ROS was accompanied by enhanced expression of mitochondrial alternative oxidase protein and its capacity. Application of AOX inhibitor SHAM inhibited the anoxic growth mediated by nitrite. In addition, nitrite improved the submergence tolerance of seedlings. Our study revealed that nitrite driven phytoglobin‐NO cycle and AOX are crucial players in anaerobic germination and growth of deepwater rice.
Molecular characterization of biphenotypic epithelioid and plexiform melanoma with deep penetrating nevus‐like features
Authors: Giubellino Alessio , Nelson Andrew C. , He Yuyu , Munro Sarah A. , Song Kyu Young , Glitza Oliva Isabella C. , Torres‐Cabala Carlos 
Published: October 2021

AbstractTumor heterogeneity is a relevant hallmark of melanoma due to the high mutation burden and immunogenicity commonly encountered. Heterogeneity at the histologic level frequently corresponds to heterogeneity at the molecular level. A better understanding of this feature of malignancy can help refine the development of predictive biomarkers and to define more effective targeted therapies. Here, we describe a case of melanoma displaying a dual phenotype: a DPN‐like/plexiform portion in conjunction with a conventional epithelioid morphology. Molecular studies revealed shared BRAF and PTEN mutations in both components but a CTNNB1 mutation was exclusively found in the DPN‐like area of the tumor, consistent with the distinct morphology observed. There was considerable heterogeneity in sequence variants identified in the two regions. Gene expression analysis highlighted differentially regulated genes between the two histologies, including a relevant cluster of genes in the receptor tyrosine kinase (RTK) family and related signaling pathways upregulated in the DPN‐like/plexiform area.
Business and human rights implications of climate change litigation: Milieudefensie et al. v Royal Dutch Shell
Authors: Macchi Chiara , van Zeben Josephine 
Published: October 2021

AbstractIn Milieudefensie et al. v Royal Dutch Shell, the District Court in the Hague ordered the respondent company to cut its global carbon dioxide emissions by 45 percent by 2030, as compared with 2019 levels. The landmark judgement represents the first imposition of a specific mitigation obligation on a private company over and above reduction targets set by existing ‘cap‐and‐trade’ regulations and/or other governmental mitigation policies. In interpreting Royal Dutch Shell's duty of care under Dutch tort law, the Court referred extensively to international soft law, including the United Nations Guiding Principles on Business and Human Rights. This note considers the implications of this case for corporate responsibility for environmental and human rights.
Legal geographies of medication abortion in the USA
Authors: Calkin Sydney 
Published: October 2021

AbstractMedication abortion with pills (mifepristone and misoprostol) challenges the spatiality of abortion provision because it creates the possibility for safe, self‐managed abortion outside of clinical infrastructure. This possibility has been contested by pro‐ and anti‐abortion actors for as long as medication abortion has been in existence. In this paper, I offer a legal geography account of medication abortion technology that examines how medication abortion has been regulated in the United States. Conceptually, the paper uses a legal geography methodology to probe the social spatialities that abortion laws construct. Empirically, the paper analyses trends in legislation to restrict medication abortion and two significant court challenges where abortion providers brought suit against medication abortion restrictions. Drawing on legislation and litigation over mifepristone, I demonstrate that restrictions on it function by anchoring mifepristone inside the clinical spaces and regulatory frameworks established for surgical abortion. In this way, mifepristone regulations circumscribe its availability in order to prevent the creation of alternative models for abortion provision that could re‐arrange its geography and expand abortion access.