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A tetravalent nanovaccine that inhibits growth of HPV-associated head and neck carcinoma via dendritic and T cell activation.
Get PDFThe global incidence of human papillomavirus (HPV) associated head and neck carcinoma is on the rise, in response to this a tetravalent therapeutic vaccine named Qβ-HPVag was developed. This vaccine, utilizing virus-like particles (VLPs) loaded with toll-like receptor ligands and chemically coupled to four HPV16-derived peptides, demonstrated strong anti-tumor effects in a murine head and neck cancer model. Qβ-HPVag impeded tumor progression, increased infiltration of HPV-specific T cells, and significantly improved survival. The vaccine`s efficacy was associated with immune repolarization in the tumor microenvironment, characterized by expanded activated dendritic cell subsets (cDC1, cDC2, DC3). Notably, mice responding to treatment exhibited a higher percentage of migratory DC3 cells expressing CCR7. These findings suggest promising prospects for optimized VLP-based vaccines in treating HPV-associated head and neck cancer
Automated astronaut traverses with minimum metabolic workload: Accessing permanently shadowed regions near the lunar south pole
No full textThe Artemis exploration zone is a topographically complex impact-cratered terrain. Steep undulating slopes pose a challenge for walking extravehicular activities (EVAs) anticipated for the Artemis III and subsequent missions. Using 5 m/pixel Lunar Orbiter Laser Altimeter (LOLA) measurements of the surface, an automated Python pipeline was developed to calculate traverse paths that minimize metabolic workload. The tool combines a Monte Carlo method with a minimum-cost path algorithm that assesses cumulative slope over distances between a lander and stations, as well as between stations. To illustrate the functionality of the tool, optimized paths to permanently shadowed regions (PSRs) are calculated around potential landing sites 001, nearby location 001(6), and 004, all within the Artemis III ‘Connecting Ridge’ candidate landing region. We identified 521 PSRs and computed (1) traverse paths to accessible PSRs within 2 km of the landing sites, and (2) optimized descents from host crater rims into each PSR. Slopes are limited to 15° and previously identified boulders are avoided. Surface temperature, astronaut body illumination, regolith bearing capacity, and astronaut-to-lander direct view are simultaneously evaluated. Travel times are estimated using Apollo 12 and 14 walking EVA data. A total of 20 and 19 PSRs are accessible from sites 001 and 001(6), respectively, four of which maintain slopes <10°. Site 004 provides access to 11 PSRs, albeit with higher EVA workloads. From the crater rims, 94 % of PSRs can be accessed. All round-trip traverses from potential landing sites can be performed in under 2 h with a constant walk. Traverses and descents to PSRs are compiled in an atlas to support Artemis mission planning
The Weaver’s Signature? The Division of Labour within the Production of Lampas Woven Silks
No full textTrois gens de lettres copistes chez Voltaire : Henri Rieu, Simon Bigex et Joseph Marie Durey de Morsan
No full textVoltaire a été assez peu étudié en tant qu’écrivain qui collabore avec d’autres écrivains. Cet aspect collaboratif de certains de ses écrits figure certes dans l’apparat critique de textes individuels ou dans des articles à leur sujet, mais il n’est jamais le sujet principal. Quand et comment Voltaire collabore-t-il avec ou fait-il appel à d’autres ? Nous souhaitons étudier ces questions, et les prolonger en tentant de cerner ses méthodes d’écriture lorsqu’Henri Rieu, Simon Bigex et Joseph Marie Durey de Morsan travaillent pour lui dans les années 1760 et 1770, à l’époque où il habite au château de Ferney, près de Genève. Habituellement décrits aujourd’hui comme des secrétaires ou des copistes, eux-mêmes se désignaient, ou leurs contemporains les désignaient, comme des hommes de lettres
Bioglass/ceria nanoparticle hybrids for the treatment of seroma: a comparative long-term study in rats.
Get PDFBackground: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism. Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides. Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy
All but Small: miRNAs from Wharton's Jelly-Mesenchymal Stromal Cell Small Extracellular Vesicles Rescue Premature White Matter Injury after Intranasal Administration.
Get PDFWhite matter injury (WMI) is a common neurological issue in premature-born neonates, often causing long-term disabilities. We recently demonstrated a key beneficial role of Wharton's jelly mesenchymal stromal cell-derived small extracellular vesicles (WJ-MSC-sEVs) microRNAs (miRNAs) in WMI-related processes in vitro. Here, we studied the functions of WJ-MSC-sEV miRNAs in vivo using a preclinical rat model of premature WMI. Premature WMI was induced in rat pups through inflammation and hypoxia-ischemia. Small EVs were purified from the culture supernatant of human WJ-MSCs. The capacity of WJ-MSC-sEV-derived miRNAs to decrease microglia activation and promote oligodendrocyte maturation was evaluated by knocking down (k.d) DROSHA in WJ-MSCs, releasing sEVs containing significantly less mature miRNAs. Wharton's jelly MSC-sEVs intranasally administrated 24 h upon injury reached the brain within 1 h, remained detectable for at least 24 h, significantly reduced microglial activation, and promoted oligodendrocyte maturation. The DROSHA k.d in WJ-MSCs lowered the therapeutic capabilities of sEVs in experimental premature WMI. Our results strongly indicate the relevance of miRNAs in the therapeutic abilities of WJ-MSC-sEVs in premature WMI in vivo, opening the path to clinical application
Chimney Stenting vs BASILICA for Prevention of Acute Coronary Obstruction During Transcatheter Aortic Valve Replacement.
No full textBACKGROUND
Coronary obstruction (CO) is a potentially life-threatening complication of transcatheter aortic valve replacement (TAVR). Chimney stenting or leaflet laceration with transcatheter electrosurgery (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction [BASILICA]) are 2 techniques developed to prevent CO.
OBJECTIVES
The aim of the present study was to compare periprocedural and 1-year outcomes of chimney and BASILICA in TAVR patients at high risk of CO.
METHODS
This multicenter observational registry enrolled consecutive TAVR patients at high risk of CO, undergoing either preventive chimney stenting or BASILICA. Clinical success was defined as successful performance of the chimney or BASILICA technique without clinically relevant ostial CO. The primary endpoint was major adverse cardiovascular events, a composite of death, myocardial infarction, stroke, or unplanned target lesion coronary revascularization at 1 year.
RESULTS
A total of 168 patients were included: 71 (42.3%) received chimney stenting, and 97 (57.7%) underwent BASILICA. Patients undergoing BASILICA had higher preprocedural risk of CO, as indicated by lower sinotubular junction height (18.2 ± 4.8 mm vs 14.8 ± 3.4 mm; P < 0.001) and diameter (28.2 ± 4.5 vs 26.8 ± 3.4; P = 0.029). Rates of periprocedural complications were similar between the 2 groups. Clinical success was 97.2% and 96.9% in chimney and BASILICA, respectively (P = 0.92). At 1-year follow-up, the cumulative incidence of major adverse cardiovascular events was 18.7% (95% CI: 11%-30.6%) in the chimney group and 19.9% (95% CI: 12.1%-31.5%) in the BASILICA group (log-rank P = 0.848), whereas chimney was associated with a numerically higher cardiovascular mortality than BASILICA (6.7% vs 1.3%; log-rank P = 0.168).
CONCLUSIONS
Chimney stenting and BASILICA effectively prevent TAVR-induced acute CO. Both techniques seem to have comparable acceptable periprocedural and 1-year outcomes
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