bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK Cell Maturation and Function in C57BL/6 Mice Are Altered by Caloric Restriction
Authors: Clinthorne Jonathan F. , Beli Eleni , Duriancik David M. , Gardner Elizabeth M. 
Published: December 2012

Abstract
NK cells are a heterogenous population of innate lymphocytes with diverse functional attributes critical for early protection from viral infections. We have previously reported a decrease in influenza-induced NK cell cytotoxicity in 6-mo-old C57BL/6 calorically restricted (CR) mice. In the current study, we extend our findings on the influence of CR on NK cell phenotype and function in the absence of infection. We demonstrate that reduced mature NK cell subsets result in increased frequencies of CD127+ NK cells in CR mice, skewing the function of the total NK cell pool. NK cells from CR mice produced TNF-α and GM-CSF at a higher level, whereas IFN-γ production was impaired following IL-2 plus IL-12 or anti-NK1.1 stimulation. NK cells from CR mice were highly responsive to stimulation with YAC-1 cells such that CD27−CD11b+ NK cells from CR mice produced granzyme B and degranulated at a higher frequency than CD27−CD11b+ NK cells from ad libitum fed mice. CR has been shown to be a potent dietary intervention, yet the mechanisms by which the CR increases life span have yet to be fully understood. To our knowledge, these findings are the first in-depth analysis of the effects of caloric intake on NK cell phenotype and function and provide important implications regarding potential ways in which CR alters NK cell function prior to infection or cancer.
Microparticles from Mycobacteria-Infected Macrophages Promote Inflammation and Cellular Migration
Authors: Walters Shaun B. , Kieckbusch Jens , Nagalingam Gayathri , Swain Ashleigh , Latham Sharissa L. , Grau Georges E. R. , Britton Warwick J. , Combes Valéry , Saunders Bernadette M. 
Published: December 2012

AbstractMycobacterium tuberculosis infection is characterized by a strong inflammatory response whereby a few infected macrophages within the granuloma induce sustained cellular accumulation. The mechanisms coordinating this response are poorly characterized. We hypothesized that microparticles (MPs), which are submicron, plasma membrane-derived vesicles released by cells under both physiological and pathological conditions, are involved in this process. Aerosol infection of mice with M. tuberculosis increased CD45+ MPs in the blood after 4 wk of infection, and in vitro infection of human and murine macrophages with mycobacteria enhanced MP release. MPs derived from mycobacteria-infected macrophages were proinflammatory, and when injected into uninfected mice they induced significant neutrophil, macrophage, and dendritic cell recruitment to the injection site. When incubated with naive macrophages, these MPs enhanced proinflammatory cytokine and chemokine release, and they aided in the disruption of the integrity of a respiratory epithelial cell monolayer, providing a mechanism for the egress of cells to the site of M. tuberculosis infection in the lung. In addition, MPs colocalized with the endocytic recycling marker Rab11a within macrophages, and this association increased when the MPs were isolated from mycobacteria-infected cells. M. tuberculosis–derived MPs also carried mycobacterial Ag and were able to activate M. tuberculosis–specific CD4+ T cells in vivo and in vitro in a dendritic cell–dependent manner. Collectively, these data identify an unrecognized role for MPs in host response against M. tuberculosis by promoting inflammation, intercellular communication, and cell migration.
Sequential Engagement of FcεRI on Mast Cells and Basophil Histamine H4 Receptor and FcεRI in Allergic Rhinitis
Authors: Shiraishi Yoshiki , Jia Yi , Domenico Joanne , Joetham Anthony , Karasuyama Hajime , Takeda Katsuyuki , Gelfand Erwin W. 
Published: December 2012

Abstract
Histamine H4 receptor (H4R)–deficient mice (H4R−/−), H4R antagonist–treated wild-type (WT) mice, and WT mice depleted of basophils failed to develop early (EPR) or late phase (LPR) nasal responses following allergen sensitization and challenge. Basophil transfer from WT but not H4R−/− mice restored the EPR and LPR in H4R−/− mice. Following passive sensitization with OVA-specific IgE, FcεRI−/− recipients of WT basophils plus OVA and histamine developed an EPR and LPR. OVA-IgE passively sensitized FcεRI−/− recipients of H4R−/− basophils and OVA and histamine challenge failed to develop an EPR or LPR, and basophils were not detected in nasal tissue. In contrast, recipients of basophils from IL-13−/− and IL-4−/−/IL-13−/− mice developed an EPR but not an LPR. These results demonstrate the development of allergic rhinitis proceeded in two distinct stages: histamine release from FcεRI-activated mast cells, followed by histamine-mediated recruitment of H4R-expressing basophils to the nasal cavity and activation through FcεRI.
PGE2 Induces Macrophage IL-10 Production and a Regulatory-like Phenotype via a Protein Kinase A–SIK–CRTC3 Pathway
Authors: MacKenzie Kirsty F. , Clark Kristopher , Naqvi Shaista , McGuire Victoria A. , Nöehren Gesa , Kristariyanto Yosua , van den Bosch Mirjam , Mudaliar Manikhandan , McCarthy Pierre C. , Pattison Michael J. , Pedrioli Patrick G. A. , Barton Geoff J. , Toth Rachel , Prescott Alan , Arthur J. Simon C. 
Published: December 2012

Abstract
The polarization of macrophages into a regulatory-like phenotype and the production of IL-10 plays an important role in the resolution of inflammation. We show in this study that PGE2, in combination with LPS, is able to promote an anti-inflammatory phenotype in macrophages characterized by high expression of IL-10 and the regulatory markers SPHK1 and LIGHT via a protein kinase A–dependent pathway. Both TLR agonists and PGE2 promote the phosphorylation of the transcription factor CREB on Ser133. However, although CREB regulates IL-10 transcription, the mutation of Ser133 to Ala in the endogenous CREB gene did not prevent the ability of PGE2 to promote IL-10 transcription. Instead, we demonstrate that protein kinase A regulates the phosphorylation of salt-inducible kinase 2 on Ser343, inhibiting its ability to phosphorylate CREB-regulated transcription coactivator 3 in cells. This in turn allows CREB-regulated transcription coactivator 3 to translocate to the nucleus where it serves as a coactivator with the transcription factor CREB to induce IL-10 transcription. In line with this, we find that either genetic or pharmacological inhibition of salt-inducible kinases mimics the effect of PGE2 on IL-10 production.
Representaciones sociales y prácticas ciudadanas en la comunidad rural: Un aporte desde la comunicación estratégica
Authors: Trimano Luciana , Emanuelli Paulina Beatriz 
Published: December 2012

La comunidad de Las Calles, ubicada en el Valle de Traslasierra, al oeste de la provincia de Córdoba (Argentina), se caracteriza por la combinación de lo rural y lo turístico; es escenario de un amplio movimiento de emigración de la ciudad al campo. En este sentido, conviven en dicha sociedad grupos culturales diversos y disímiles identidades. Entendiendo que esos grupos culturales forman parte de la “cultura” como espacio estratégico de comprensión de las tensiones que desgarran y recomponen el “estar juntos”.
La presentación plantea el análisis de las representaciones sociales e interacciones de actores de culturas emergentes (hippies) y preexistentes (paisas) en esta territorialidad rural y la aparición de nuevos repertorios y prácticas ciudadanas. Las interacciones y prácticas ciudadanas demandan la revisión y rediseño de “actuales” políticas de gestión e integración sociocultural. Desde ese lugar, la comunicación estratégica puede y debe realizar un aporte, tendiente a promover el desarrollo territorial y local.
Morfología de los medios y empresas de comunicación del Ecuador
Authors: Coronel-Salas Gabriela , Catalina Mier-Sanmartín Catalina , Barrazueta-Molina Patricio , Ortiz León Carlos , González Rentería Verónica , Yaguache Quichimbo Jenny , Paladines Galarza Fanny , Valarezo-González Karina Paola , Banegas Diana , Samaniego Santiago 
Published: December 2012

La escasez de información en relación a la situación de las empresas de comunicación de Ecuador, motivó al Departamento de Ciencias de la Comunicación de la Universidad Técnica Particular de Loja (UTPL) a desarrollar un mapeo de medios, comunicación, productoras, agencias de publicidad y relaciones públicas del país. La necesidad de disponer de un sitio de consulta y de referencia, respecto a temas de comunicación, es aún latente en Ecuador. Si bien existen algunos aportes, tanto por parte de organismos estatales como de privados, para construir repositorios físicos o virtuales, éstos se han limitado a presentar información básica de contacto y muchas veces desactualizada. Con una muestra de más de 1000 medios se accede a conocer su forma y fondo, en si, su morfología distribuida en organización legal y societaria, situación geográfica, contenidos, alcance, y servicios prestados. La misma, es una aproximación a la realidad informativa que vive el país y que forma parte de la macro investigación denominada “Mapa de la comunicación de Ecuador”.
Characterization of Oligo(Ethylene Glycol) and Oligoglycerol Functionalized Poly(Ether Imide) by Angle-Dependent X-Ray Photoelectron Spectroscopy
Authors: von Ruesten-Lange Maik , Luetzow Karola , Neffe Axel T. , Lendlein Andreas 
Published: December 2012

Purpose Previous investigations have shown that poly(ether imide) (PEI) membranes can be functionalized with aminated macromolecules. In this study we explored whether the characterization of PEI functionalized with oligo(ethylene glycol) (OEG) or linear, side chain methylated oligoglycerols (OGMe), by angle-dependent X-ray induced photoelectron spectroscopy (XPS) can be used to prove the functionalization, give insight into the reaction mechanism and reveal the spatial distribution of the grafts. Methods PEI membranes were functionalized under alkaline conditions using an aqueous solution with 2 wt% of α-amino-ω-methoxy oligo(ethylene glycol) (Mn = 1,320 g·mol−1) or linear, side chain methylated monoamine oligoglycerols (Mn = 1,120, 1,800 or 2,270 g·mol−1), respectively. The functionalized membranes were investigated using XPS measurements at different detector angles to enable comparison between the signals related to the bulk and surface volume and were compared with untreated and alkaline-treated PEI membranes. Results While at a perpendicular detector angle the bulk signals of the PEI were prominent, at larger surface volume-related detector angles, the signals for OGMe and OEG were determinable. Conclusion The surface functionalization of PEI with OEG and OGMe could be verified by the angle-dependent XPS. The observations proved the functionalization at the PEI surface, as the polyethers were detected at angles providing signals of the surface volume. Furthermore, the chemical functions determined verified a covalent binding via the nucleophilic addition of the amine functionalized OGMe and OEG to the PEI imide function.
Focalization and Embedded Speech in Andromache’s Iliadic Laments
Authors: Muich Rebecca 
Published: December 2012

AbstractAndromache’s laments in the Iliad use tertiary focalization and embedded speech as a means of engaging with masculine experiences within the feminine lament tradition. The focalized masculine experiences draw the audience’s attention away from the masculinity described by the main narrative of the Iliad, which promotes an aggressive pursuit of kleos even to death and refocuses attention on a nonmartial masculinity centered on the oikos. Andromache’s laments do not merely criticize Hector’s choice to sacrifice his oikos in his pursuit of kleos, but also argue that a warrior is valuable to his community not only as protector, but also as engaged participant in social structures that support the community as a whole.
Protagoras’s Talking Head: Corporeality, Rationality, and Self-Refutation in Theaetetus 171c-d
Authors: Giannopoulou Zina 
Published: December 2012

Abstract
In this paper I argue that Socrates’s evocation of Protagoras’s ghost in Theaetetus foregrounds and assaults the sophist’s humanity in its physical and mental manifestations: his ghostliness renders him unfit to evaluate a doctrine that makes human beings the measure of all things, while his haste to return to the Underworld prevents him from partaking in dialectic and exhibiting his rationality. I also show the contextual relevance of the episode by suggesting that the passage is the last act of a three-act parody of Protagoras’s humanity, which aims to refute the man-as-measure doctrine. The first act is the so-called Protagoras’s Apology (165e8-168c1), the second act is the self-refutation argument (170a6-171c7), and the third act is the sophist’s ghostly appearance (171c10-d3).
Conspiracy Rhetoric in Cicero’sVerrines
Authors: Spencer Walter E. 
Published: December 2012

AbstractThis article offers an examination of the language of conspiracy in Cicero’s Verrines. Cicero chooses to fashion a recognizable portrait of Roman conspiracy that represents Verres and his societas as a group of like-minded coconspirators, though they have committed no act that suggests political revolution. Cicero’s diction, imagery, and themes parallel the rhetorical strategies often found in conspiracy narratives and echo especially the orator’s own portrait of Catiline.
Tracing Furrows in the Satiric Dust: Echoes of Horace’sEpistlesin Juvenal 1
Authors: Larmour David H. J. 
Published: December 2012

AbstractJuvenal’s Satire 1 can be read as a journey across Rome in the course of which the satirist undertakes a reformulation of Lucilian libertas into Horatian introspection. This journey is accompanied by contrasting moments of high and low self-positioning on the part of the speaker. Examining the opening (1-21) and closing (155-71) lines, especially the Tigillinus passage and the image of the satirist’s charred corpse tracing a furrow through the sand of the arena (157), leads us to possible sources of inspiration in Horace’sEpistles, especially 1.1.1-9, 1.19.35-49, and 2.2.95-108. Juvenal’s Satire 7 picks up some of these themes, but by then the danger is primarily to the satirist’s financial rather than his physical security.
Why Evidence Generation Should Matter to Payers and How They Can Help
Authors: Abbasi Ali B. , Curtis Lesley H. , Fleisher Lee A. , Califf Robert M. 
Published: July 2024

ImportanceThe US leads the world in bringing new medical products to market, but the ability to generate evidence to inform clinical practice in postmarket settings needs improvement. Although a diverse group of stakeholders is working to improve postmarket evidence generation, the role of private payers has been underappreciated.ObservationsPayers are crucial allies in improving evidence generation because better data would better inform coverage decisions, their policies and practices influence the conduct of care and research, and their claims data are a source of real-world evidence used in medical product evaluation. In addition, payers have a stake in improving evidence generation because the kinds of evidence needed to inform health care and coverage decisions are often not available when a product enters the market and may not be generated without their involvement. Here, we describe several key steps payers could take to improve evidence generation, including participating in efforts to reduce administrative and financial barriers to the conduct of clinical trials, directly incentivizing evidence generation on high-priority questions by funding potential cost-saving trials, increasing engagement with the medical products industry on evidentiary needs for coverage decisions, and improving usability of claims data by reducing data lags and routinely recording unique device identifiers. Broad payer engagement with US Food and Drug Administration recommendations regarding evidence generation will ensure that the opportunities to participate in clinical research are extended to all communities and that evidence needed to inform care is generated in trials and surveillance systems that reflect the clinical reality across the US.Conclusions and RelevanceIncreasing payer involvement in evidence generation can benefit all participants in the medical innovation ecosystem. The importance of payers in these efforts will continue to grow in response to imperatives to increase integration of care and research, engage a diverse set of communities in clinical research, and move toward alternative payment models.
Routine Electrocardiogram Screening and Cardiovascular Disease Events in Adults
Authors: Yagi Ryuichiro , Mori Yuichiro , Goto Shinichi , Iwami Taku , Inoue Kosuke 
Published: July 2024

ImportanceThe resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the prognostic significance of ECG in clinical practice settings.ObjectiveTo investigate the association between ECG abnormalities and CVD outcomes in a working-age population.Design, Setting, and ParticipantsThis nationwide cohort study included individuals aged 35 to 65 years from the Japan Health Insurance Association database, which covers approximately 40% (30 million) of the working-age population in Japan. Data from April 1, 2015, to March 31, 2022, were included, and analysis was conducted from October 1, 2022, to April 11, 2024.ExposuresBaseline ECG status (normal, 1 minor abnormality, ≥2 minor abnormalities, or major abnormality).Main Outcomes and MeasuresThe primary outcome was a composite of overall death and CVD hospital admission due to myocardial infarction, stroke, or heart failure. The secondary outcome was developing a new major ECG abnormality over the years of screening.ResultsOf 3 698 429 individuals enrolled in the nationwide annual health check program (mean [SD] age, 47.1 [8.5] years; 66.6% male), 623 073 (16.8%) had 1 minor ECG abnormality, 144 535 (3.9%) had 2 or more minor ECG abnormalities, and 56 921 (1.5%) had a major ECG abnormality. During a median follow-up of 5.5 (IQR, 3.4-5.7) years, baseline ECG abnormality was independently associated with an increased incidence of the composite end points of overall death and CVD admission compared with normal ECG (incidence rates per 10 000 person-years: 92.7 [95% CI, 92.2-93.2] for normal ECG, 128.5 [95% CI, 127.2-129.9] for 1 minor ECG abnormality, 159.7 [95% CI, 156.6-162.9] for ≥2 minor ECG abnormalities, and 266.3 [95% CI, 259.9-272.3] for a major ECG abnormality; adjusted hazard ratios: 1.19 [95% CI, 1.18-1.20] for 1 minor ECG abnormality, 1.37 [95% CI, 1.34-1.39] for ≥2 minor ECG abnormalities, and 1.96 [95% CI, 1.92-2.02] for a major ECG abnormality). Furthermore, the presence and number of minor ECG abnormalities were associated with an increased incidence of developing new major ECG abnormalities (incidence rates per 10 000 person-years: 85.1 [95% CI, 84.5-85.5] for normal ECG, 217.2 [95% CI, 215.5-219.0] for 1 minor ECG abnormality, and 306.4 [95% CI, 302.1-310.7] for ≥2 minor ECG abnormalities; and adjusted hazard ratios: 2.52 [95% CI, 2.49-2.55] for 1 minor ECG abnormality and 3.61 [95% CI, 3.55-3.67] for ≥2 minor ECG abnormalities). Associations were noted regardless of baseline CVD risk.Conclusions and RelevanceThe findings of this study suggest that the potential role of routine ECG screening for early prevention of CVD events, along with the optimal follow-up strategy, should be examined in future studies.
Two-Year Outcomes of Umbilical Cord Milking in Nonvigorous Infants
Authors: Katheria Anup C. , El Ghormli Laure , Clark Erin , Yoder Bradley , Schmölzer Georg M. , Law Brenda H. Y. , El-Naggar Walid , Rittenberg David , Sheth Sheetal , Martin Courtney , Vora Farha , Lakshminrusimha Satyan , Underwood Mark , Mazela Jan , Kaempf Joseph , Tomlinson Mark , Gollin Yvonne , Rich Wade , Morales Ana , Varner Michael , Poeltler Debra , Vaucher Yvonne , Mercer Judith , Finer Neil , Rice Madeline Murguia 
Published: July 2024

ImportanceCompared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic hypothermia in nonvigorous near-term and full-term infants. However, UCM postdischarge outcomes are not known.ObjectiveTo determine the 2-year outcomes of children randomized to UCM or ECC at birth in the Milking in Nonvigorous Infants (MINVI) trial.Design, Setting, and ParticipantsA secondary analysis to evaluate longer-term outcomes of a cluster-randomized crossover trial was conducted from January 9, 2021, to September 25, 2023. The primary trial took place in 10 medical centers in the US, Canada, and Poland from January 5, 2019, to June 1, 2021, and hypothesized that UCM would reduce admission to the neonatal intensive care unit compared with ECC; follow-up concluded September 26, 2023. The population included near-term and full-term infants aged 35 to 42 weeks’ gestation at birth who were nonvigorous; families provided consent to complete developmental screening questionnaires through age 2 years.InterventionUCM and ECC.Main Outcomes and MeasuresAges and Stages Questionnaire, 3rd Edition (ASQ-3) and Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) questionnaires at ages 22 to 26 months. Intention-to-treat analysis and per-protocol analyses were used.ResultsAmong 1730 newborns from the primary trial, long-term outcomes were evaluated in 971 children (81%) who had ASQ-3 scores available at 2 years or died before age 2 years and 927 children (77%) who had M-CHAT-R/F scores or died before age 2 years. Maternal and neonatal characteristics by treatment group were similar, with median birth gestational age of 39 (IQR, 38-40) weeks in both groups; 224 infants (45%) in the UCM group and 201 (43%) in the ECC group were female. The median ASQ-3 total scores were similar (UCM: 255 [IQR, 225-280] vs ECC: 255 [IQR, 230-280]; P = .87), with no significant differences in the ASQ-3 subdomains. Medium- to high-risk M-CHAT-R/F scores were also similar (UCM, 9% [45 of 486] vs ECC, 8% [37 of 441]; P = .86).Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial among late near-term and full-term infants who were nonvigorous at birth, ASQ-3 scores at age 2 years were not significantly different between the UCM and ECC groups. Combined with previously reported important short-term benefits, this follow-up study suggests UCM is a feasible, no-cost intervention without longer-term neurodevelopmental risks of cord milking in nonvigorous near-term and term newborns.Trial RegistrationClinicalTrials.gov Identifier: NCT03631940