bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Pharmacokinetic Interactions of the HCV Ns5A Replication Complex Inhibitor Daclatasvir with Antiretroviral Agents: Ritonavir-Boosted Atazanavir, Efavirenz and Tenofovir
Authors: Bifano Marc , Hwang Carey , Oosterhuis Berend , Hartstra Jan , Grasela Dennis , Tiessen Renger , Velinova-Donga Maria , Kandoussi Hamza , Sevinsky Heather , Bertz Richard 
Published: August 2013

Background Approximately one-third of all HIV-infected individuals are coinfected with HCV, many of whom will receive concomitant treatment for both infections. With the advent of direct-acting antivirals (DAAs) for HCV, potential drug interactions between antiretrovirals and DAAs require evaluation prior to co-therapy. Methods Three open-label studies were conducted in healthy subjects to assess potential interactions between the investigational first-in-class HCV NS5A replication complex inhibitor daclatasvir and representative antiretrovirals atazanavir/ritonavir, efavirenz and tenofovir disoproxil fumarate. Results Target exposure was that of 60 mg daclatasvir alone. Dose-normalized (60 mg) geometric mean ratios of daclatasvir AUCτ for 20 mg ± atazanavir/ritonavir (2.10 [90% CI 1.95, 2.26]) and 120 mg ± efavirenz (0.68 [0.60, 0.78]) showed less than the three-fold elevation and two-fold reduction, respectively, in systemic exposure predicted by prior interaction studies with potent inhibitors/inducers of CYP3A4. Daclatasvir dose adjustment to 30 mg once daily with atazanavir/ritonavir and 90 mg once daily with efavirenz is predicted to normalize AUCτ relative to the target exposure (geometric mean ratios 1.05 [0.98, 1.13] and 1.03 [0.90, 1.16], respectively). Atazanavir exposure (Cmax, AUCτ and C24 trough) and efavirenz Ctrough under coadministration were similar to historical data without daclatasvir. No clinically relevant interactions between daclatasvir and tenofovir disoproxil fumarate were observed for either drug, and no dosing adjustments were indicated. Daclatasvir was well tolerated in all three studies. Conclusions The pharmacokinetic data support coadministration of daclatasvir with atazanavir/ritonavir, efavirenz and/or tenofovir. A Phase III study in HIV–HCV coinfection has commenced using the described dose modifications.
Osmose : note réflexive sur le couple Mexique-États-Unis
Authors: Bataillon Claude 
Published: August 2013

L’osmose entre Mexique et États-Unis remonte à 1848, pour des raisons géopolitiques : établissement d’une frontière commune entre deux États-nations inégaux, qui postérieurement ont évité tout conflit armé important. Pour le Mexique, les flux entre les deux pays sont essentiels : flux commerciaux, financiers et migratoires (de travail ou de tourisme), car le partenaire presque unique est les États-Unis. Chez ces derniers, les Latinos sont devenus la minorité principale, dans laquelle les Mexicains sont prédominants.
Le diagnostic psychiatrique à l'ère de la médecine industrielle
Authors: Advenier Frédéric , Kapsambelis Vassilis 
Published: August 2013

L’organisation actuelle des soins à l’hôpital est basée sur l’idée d’une production d’actes de soins au sein d’un plateau technique. Cette approche tend à formaliser une relation de correspondance univoque entre un diagnostic et un acte technique, en fonction d’un coût efficacité optimal. Des ébauches d’application en psychiatrie sont en cours et objectivent trois problèmes pratiques : la dispersion des plateaux techniques entre l’ambulatoire et l’intrahospitalier ; l’inadaptation des formes traditionnelles de diagnostics à être mises en lien univoque avec des coûts de production de soins ; l’émergence de critères aspécifiques sur le plan médical mais sociaux (autonomie, adhésion aux soins, soutien de l’entourage du patient) expliquant de manière pertinente les disparités de coût de prises en charge. Nous tentons d’expliquer ces faits en éclairant les problèmes épistémologiques liés à la pose d’un diagnostic.
Suspendre le DSM
Authors: Drossart Francis 
Published: August 2013

La partialité des classifications des maladies mentales issues du DSM III n’est plus à démontrer. Privilégiant une approche purement symptomatique et comportementale, elles visent à promouvoir, sous prétexte d’une vision « athéorique », le refus organisé, chez les cliniciens, de toute psychopathologie. L’auteur revendique ici, à tout le moins, le droit à une mise en suspens de cette classification lors de la rencontre intersubjective censée avoir lieu entre le psychiatre (ou le psychologue) et son patient.
Les névroses mixtes à l'épreuve de la démarche diagnostique : destin freudien des leçons de Charcot
Authors: Lepoutre Thomas , Villa François 
Published: August 2013

On s’attache ici à rouvrir la question du diagnostic, telle qu’elle se déploie le long du trajet historique qui va de Charcot à Freud. Cela impose de réévaluer l’impulsion profonde qu’exerce la démarche nosologique de Charcot dans le mouvement de la découverte freudienne : c’est ainsi la première parole freudienne sur le champ des névroses qu’il s’agit de rééxhumer, pour y retrouver, derrière la « main classificatrice » de Freud, l’incidence d’un point particulier de la méthodologie de Charcot. En suivant le destin freudien des Leçons de Charcot, donc, c’est la place accordée aux névroses mixtes dans la psychopathologie de Freud qui nous permet d’épingler le rôle que tient la démarche diagnostique dans la rationalité psychanalytique.
« Orthorexie » : un questionnement psychopathologique
Authors: Kaluaratchige Elizabeth 
Published: August 2013

Cet article propose des pistes de réflexions psychopathologiques sur la pathologie dite orthorexie fortement liée aux troubles digestifs et aux antécédents anorexiques. Nos arguments sont fondés sur une observation et une analyse de l’articulation entre symptômes psychiques et somatiques, critères et indices comportementaux, par une approche transdisciplinaire et anthropologico- psychanalytique
« Le déni de grossesse » : une entité clinique valide ?
Authors: Pereira de Oliveira Céline 
Published: August 2013

La clinique du « déni de grossesse » est complexe et polymorphe. C’est pourquoi, il est plus conforme de la nommer « négations de grossesse », en lien avec les mécanismes défensifs suivants : déni, dénégation et forclusion. Cet article a pour principale visée de rendre compte de ces processus psychiques de manière différentielle, significative et compréhensive, permettant de réfléchir à notre positionnement et de proposer consécutivement, un réaménagement clinique.
Morphine Prevents Lipopolysaccharide-Induced TNF Secretion in Mast Cells Blocking IκB Kinase Activation and SNAP-23 Phosphorylation: Correlation with the Formation of a β-Arrestin/TRAF6 Complex
Authors: Madera-Salcedo Iris K. , Cruz Silvia L. , Gonzalez-Espinosa Claudia 
Published: August 2013

Abstract
We have previously shown that morphine pretreatment inhibits mast cell–dependent TNF production after LPS injection in the murine peritoneal cavity. In this study, we used bone marrow–derived mast cells (BMMCs) to investigate the molecular mechanisms of that inhibition. We found that morphine prevented LPS-induced TNF secretion in these cells. The observed inhibition was not due to morphine-induced TLR4 internalization and it was related to the blockage of preformed TNF secretion. LPS-induced TNF exocytosis in BMMCs was dependent on tetanus toxin–insensitive vesicle-associated membrane proteins and calcium mobilization, as well as PI3K, MAPK, and IκB kinase (IKK) activation. TNF secretion was also associated to the phosphorylation of synaptosomal-associated protein 23 (SNAP-23), which was found forming a complex with IKK in LPS-activated BMMCs. Morphine pretreatment prevented TLR4-dependent ERK and IKK phosphorylation. Analyzing the signaling events upstream of IKK activation, we found diminished TGF-β–activated kinase 1 (TAK1) phosphorylation and TNFR-associated factor (TRAF) 6 ubiquitination in BMMCs pretreated with morphine and stimulated with LPS. Morphine pretreatment provoked a marked increase in the formation of a molecular complex composed of TRAF6 and β-arrestin-2. Naloxone and a combination of μ and δ opioid receptor antagonists prevented morphine inhibitory actions. In conclusion, our results show that activation of μ and δ opioid receptors with morphine suppresses TLR4-induced TNF release in mast cells, preventing the IKK-dependent phosphorylation of SNAP-23, which is necessary for TNF exocytosis, and this inhibition correlates with the formation of a β-arrestin-2/TRAF6 complex. To our knowledge, these findings constitute the first evidence of molecular crosstalk between opioid receptors and the TLR4 signal transduction system in mast cells.
IL-4 and Retinoic Acid Synergistically Induce Regulatory Dendritic Cells Expressing Aldh1a2
Authors: Zhu Bing , Buttrick Thomas , Bassil Ribal , Zhu Chen , Olah Marta , Wu Chuan , Xiao Sheng , Orent William , Elyaman Wassim , Khoury Samia J. 
Published: August 2013

Abstract
Although activated inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs) are potent T cell suppressors, nonactivated IMCs and IDCs promote T cell activation and Th1/Th17 cell differentiation. In this study, we investigated how to reduce the proinflammatory properties of IMCs and IDCs and further convert them into immune regulatory dendritic cells (DCs). We found that IL-4 and retinoic acid (RA) cotreatment of GM-CSF–differentiated IDCs synergistically induced the expression of aldehyde dehydrogenase family 1, subfamily A2, a rate-limiting enzyme for RA synthesis in DCs. IL-4 plus RA–treated IDCs upregulated CD103 expression and markedly reduced the production of proinflammatory cytokines upon activation. IL-4 plus RA–treated IDCs strongly induced CD4+Foxp3+ regulatory T cell differentiation and suppressed Th1 and Th17 differentiation. Mechanistically, the transcription factors Stat6 and RA receptor β play important roles in aldehyde dehydrogenase family 1, subfamily A2, induction. In addition, IL-4 and RA signaling pathways interact closely to enhance the regulatory function of treated DCs. Adoptive transfer of IL-4 plus RA–treated DCs significantly increased regulatory T cell frequency in vivo. Direct treatment with IL-4 and RA also markedly suppressed actively induced experimental autoimmune encephalomyelitis. Our data demonstrate the synergistic effect of IL-4 and RA in inducing a regulatory phenotype in IDCs, providing a potential treatment strategy for autoimmune diseases.
MiR-210 Is Induced by Oct-2, Regulates B Cells, and Inhibits Autoantibody Production
Authors: Mok Yingting , Schwierzeck Vera , Thomas David C. , Vigorito Elena , Rayner Tim F. , Jarvis Lorna B. , Prosser Haydn M. , Bradley Allan , Withers David R. , Mårtensson Inga-Lill , Corcoran Lynn M. , Blenkiron Cherie , Miska Eric A. , Lyons Paul A. , Smith Kenneth G. C. 
Published: August 2013

Abstract
MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in the development of autoantibodies from 5 mo of age. Overexpression of MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired class-switched Ab responses, a finding confirmed in wild-type B cells transfected with a MiR-210 mimic. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, which were consistent with the transcriptomic analysis demonstrating downregulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of MiR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production.
La construction discursive de l’identité francophone en Acadie ou « comment être francophone à partir des marges » ?
Authors: Arrighi Laurence , Boudreau Annette 
Published: August 2013

L’article met l’accent sur l’apport des discours « d’autorité » dans la construction de l’idéologie du français unique, très présent dans la francophonie. Émanant des « centres » linguistiques et souvent considérés comme référence et source légitime du savoir, ces discours « savants » jouent un rôle fondamental dans la construction des représentations et idéologies linguistiques, notamment dans les milieux minoritaires, où l’examen théorique et épistémologique des « objets » minoritaires est souvent négligé au profit d’études plus empiriques. L’article interroge notamment le rôle que joue le linguiste en milieu minoritaire étant donné que ce dernier contribue parfois, à son insu, à stéréotyper certaines pratiques des francophones.
Hypoxic–Normoxic Crosstalk Activates Pro‐Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post‐Infarct Myocardium on a Chip
Authors: Khalil Natalie N. , Rexius‐Hall Megan L. , Gupta Divya , McCarthy Liam , Verma Riya , Kellogg Austin C. , Takamoto Kaelyn , Xu Maryann , Nejatpoor Tiana , Parker Sarah J. , McCain Megan L. 
Published: July 2024

AbstractMyocardial infarctions locally deprive myocardium of oxygenated blood and cause immediate cardiac myocyte necrosis. Irreparable myocardium is then replaced with a scar through a dynamic repair process that is an interplay between hypoxic cells of the infarct zone and normoxic cells of adjacent healthy myocardium. In many cases, unresolved inflammation or fibrosis occurs for reasons that are incompletely understood, increasing the risk of heart failure. Crosstalk between hypoxic and normoxic cardiac cells is hypothesized to regulate mechanisms of repair after a myocardial infarction. To test this hypothesis, microfluidic devices are fabricated on 3D printed templates for co‐culturing hypoxic and normoxic cardiac cells. This system demonstrates that hypoxia drives human cardiac fibroblasts toward glycolysis and a pro‐fibrotic phenotype, similar to the anti‐inflammatory phase of wound healing. Co‐culture with normoxic fibroblasts uniquely upregulates pro‐inflammatory signaling in hypoxic fibroblasts, including increased secretion of tumor necrosis factor alpha (TNF‐α). In co‐culture with hypoxic fibroblasts, normoxic human induced pluripotent stem cell (hiPSC)‐derived cardiac myocytes also increase pro‐inflammatory signaling, including upregulation of interleukin 6 (IL‐6) family signaling pathway and increased expression of IL‐6 receptor. Together, these data suggest that crosstalk between hypoxic fibroblasts and normoxic cardiac cells uniquely activates phenotypes that resemble the initial pro‐inflammatory phase of post‐infarct wound healing.
Copper‐Based Composites Nanoparticles Improve Triple‐Negative Breast Cancer Treatment with Induction of Apoptosis‐Cuproptosis and Immune Activation
Authors: Wang Ning , Liu Yichao , Peng Dezhou , Zhang Qiyu , Zhang Zhibo , Xu Lina , Yin Lianhong , Zhao Xuerong , Lu Zhi , Peng Jinyong 
Published: July 2024

AbstractThe synergistic effect of apoptosis and cuproptosis, along with the activation of the immune system, presents a promising approach to enhance the efficacy against triple‐negative breast cancer (TNBC). Here, two prodrugs are synthesized: a reactive oxygen species (ROS)‐responsive prodrug PEG‐TK‐DOX and a glutathione (GSH)‐responsive prodrug PEG‐DTPA‐SS‐CPT. These prodrugs are self‐assembled and chelated Cu2+ to prepare nanoparticle PCD@Cu that simultaneously loaded doxorubicin (DOX), camptothecin (CPT), and Cu2+. The elevated levels of ROS and GSH in TNBC cells disrupted the PCD@Cu structure, leading to the release of Cu+, DOX, and CPT and the depletion of GSH. DOX and CPT triggered apoptosis with immunogenic cell death (ICD) in TNBC cells. Simultaneously, PCD@Cu downregulated the expression of copper transporting ATPase 2 (ATP7B), causing a significant accumulation of copper ions in TNBC cells. This further induced the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT) and downregulation of iron‐sulfur (Fe‐S) cluster proteins, ultimately leading to cuproptosis and ICD in TNBC. In vitro and in vivo experiments confirmed that PCD@Cu induced apoptosis and cuproptosis in TNBC and activated the immune system, demonstrating strong anti‐tumor capabilities. Moreover, PCD@Cu exhibited an excellent biosafety profile. Overall, this study provides a promising strategy for effective TNBC therapy.
Infrared‐Transparent Semiconductor Membranes for Electromagnetic Interference Shielding of Millimeter Waves
Authors: Renteria Emma J. , Heileman Grant D. , Neely Jordan P. , Addamane Sadhvikas J. , Rotter Thomas J. , Balakrishnan Ganesh , Christodoulou Christos G. , Cavallo Francesca 
Published: July 2024

AbstractIt is demonstrated that single‐crystalline and highly doped GaAs membranes are excellent candidates for realizing infrared‐transparent shields of electromagnetic interference at millimeter frequencies. Measured optical transmittance spectra for the semiconductor membranes show resonant features between 750 and 2500 nm, with a 100% maximum transmittance. The shielding effectiveness of the membranes is extracted from measured scattering parameters between 65 and 85 GHz. Selected GaAs membranes and membranes/polyamide films exhibit shielding effectiveness ranging from 22 to 40 dB, which are suitable values to ensure the safe operation of infrared devices for commercial applications. Theoretical calculations based on a plane wave model show that the interplay of primary reflection and multiple internal reflections of the radio‐frequency waves results in broadband shielding capabilities of the membrane between 10 and 300 GHz.
Anomalous Radiative Transfer in Heterogeneous Media
Authors: Tommasi Federico , Pattelli Lorenzo , Cavalieri Stefano , Fini Lorenzo , Paolucci Michela , Pini Ernesto , Sassaroli Angelo , Martelli Fabrizio 
Published: July 2024

AbstractMonte Carlo (MC) simulations are the gold standard for describing various transport phenomena and have largely contributed to the understanding of these processes. However, while their implementation for classical transport governed by exponential step‐length distributions is well‐established, widely accepted approaches are still lacking for the more general class of anomalous transport phenomena. In this work, a set of rules for performing MC simulations in anomalous diffusion media is identified, which is also applicable in the case of finite‐size geometries and/or heterogeneous inclusions. The results are presented in the context of radiative transfer, however their implications extend to all types of anomalous transport. The proposed set of rules exhibits full compatibility with the pathlength invariance property for random trajectories, and with the important radiometric concept of fluence. Additionally, it reveals the counter‐intuitive possibility of introducing interfaces between independent subdomains with identical properties, which arise from the fact that non‐exponential step‐length distributions have a “memory” that can in principle be reset when traversing a boundary. These results have far‐reaching consequences not just for the physical interpretation of the corrections required to handle these discontinuities, but also for their experimental verification, due to their expected effects on the observable pathlength distributions.
Unraveling the Roles of Switching and Relaxation Times in Volatile Electrochemical Memristors to Mimic Neuromorphic Dynamical Features
Authors: Dutta Mrinmoy , Brivio Stefano , Spiga Sabina 
Published: July 2024

AbstractComputing through ensembles of interacting dynamical elements is the next frontier of the diverse field of neuromorphic computing. Spiking neural networks are one of the possible examples. Computation through dynamics and through time requires the development of novel technologies for devices with rich dynamics. Among the various candidates, the most promising ones are volatile electrochemical memristive systems that switch from high to low resistance state by voltage application and self‐recover the high resistance state after a tunable relaxation time. Such devices can perform a wide variety of computational primitives. However, a clear comprehensive picture of their possible dynamics and their physical interpretation is still missing. In the present manuscript, prototypical electrochemical silver/silicon oxide/platinum (Ag/SiOx/Pt) memristive devices are characterized to identify dynamical aspects, like integrative effects and stochastic switching. Integrative effects are evidenced both in high and low resistance states, associated to wake‐up phase and cumulative switching. All the dynamical aspects are related to characteristic switching times and relaxation times, and with reference to the electrochemical and physical processes involved in device operation. The various dynamical aspects are linked to short‐term memory effects and basic temporal processing functions based on paired‐pulse effects that are relevant for neuromorphic applications.
Striking genetic homogeneity in the widespread South American bracken
Authors: Yañez Agustina , Kinosian Sylvia P. , Ponce M. Mónica , Gutierrez Diego G. , Schwartsburd Pedro B. , Sundue Michael , Wolf Paul G. 
Published: July 2024

AbstractPremiseBracken (Pteridium, Dennstaedtiaceae) is a cosmopolitan genus of aggressive disturbance colonizers that are toxic to agricultural livestock. The taxonomy of Pteridium has been treated in multiple schemes, ranging from one to six species worldwide, with numerous subspecies and varieties. Recent work has focused on the worldwide distribution and systematics of the bracken fern, but South America has been poorly represented. We present the first continent‐wide sampling and analysis of Pteridium esculentum, a Southern Hemisphere diploid species.MethodsWithin South America, P. esculentum has several morphotypes, distinguished into subspecies by variation in indument and lamina architecture. We used double digest restriction site‐associated DNA sequencing (ddRADSeq) to assess the phylogenetic relationships of P. esculentum subspecies.ResultsWe found a striking genetic homogeneity in the species, being able to support only two morphotypes from molecular data: P. e. arachnoideum and P. e. campestre. We had high confidence for shallow and deep phylogenetic relationships, but less support for relationships among crown groups.ConclusionsWe describe an east‐west geographic pattern that would explain the relationships between populations; and, in contrast to previous studies, we detected differences with P. esculentum from Australia. These results will lay the foundations for studying variations in this species' behavior as a weed, as well as its impact on the production of agricultural livestock in South America.