The aim of this analysis was to assess the cost-effectiveness of the EmboTrap Revascularization Device compared with the Solitaire™ Revascularization Device and Trevo Retriever for the treatment of acute ischemic stroke (AIS) from the perspective of the Chinese healthcare system. According to MASTRO I, a recent living systematic literature review and meta-analysis, mechanical thrombectomy (MT) with EmboTrap in the treatment of AIS resulted in better functional outcomes compared with the use of Solitaire or Trevo. Based on the proportion of patients that achieved 90-day modified Rankin Scale (mRS) scores of 0-2, 3-5 and 6 reported in MASTRO I, a combined 90-day short-term decision tree and Markov model with a 10-year time horizon was used to compare the cost-effectiveness of the three devices.
View Article and Find Full Text PDFAn effective human immunodeficiency virus 1 (HIV-1) vaccine will most likely have to elicit broadly neutralizing antibodies (bNAbs) to overcome the sequence diversity of the envelope glycoprotein (Env). So far, stabilized versions of Env, such as SOSIP trimers, have been able to induce neutralizing antibody (NAb) responses, but those responses are mainly strain-specific. Here we attempted to broaden NAb responses by using a multivalent vaccine and applying a number of design improvements.
View Article and Find Full Text PDFUnlabelled: The EORTC 22922/10925 trial aimed to investigate the impact on overall survival (OS) of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I-III. Surgery for the primary tumour and axillary lymph nodes, chest wall RT, boost RT after whole breast RT in breast conserving therapy (BCT), RT to operated axilla, and systemic therapy were per physician's preference. The aim of the current analysis is to assess breast cancer outcomes according to different locoregional and systemic therapy used in the trial.
View Article and Find Full Text PDFLassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized.
View Article and Find Full Text PDFBackground And Purpose: Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) relies on efficient tracking of aspiration catheters through complex vascular anatomies. Differences in catheter design lead to variation in tracking performance which may only become apparent after use in patients. We developed an methodology for evaluating aspiration catheter performance under a variety of pre-defined circumstances, that can be used during catheter development for design optimization.
View Article and Find Full Text PDFThin-film stacks | consisting of a ferromagnetic-metal layer and a heavy-metal layer are spintronic model systems. Here, we present a method to measure the ultrabroadband spin conductance across a layer between and at terahertz frequencies, which are the natural frequencies of spin-transport dynamics. We apply our approach to MgO tunneling barriers with thickness = 0-6 Å.
View Article and Find Full Text PDFWe study the spatiotemporal dynamics of ultrafast electron spin transport across nanometer-thick copper layers using ultrabroadband terahertz emission spectroscopy. Our analysis of temporal delays, broadening, and attenuation of the spin-current pulse reveals ballisticlike propagation of the pulse peak, approaching the Fermi velocity, and diffusive features including a significant velocity dispersion. A comparison to the frequency-dependent Fick's law identifies the diffusion-dominated transport regime for distances >2 nm.
View Article and Find Full Text PDFVaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Early antibody responses to easily accessible epitopes on these antigens are directed to non-neutralizing epitopes instead of bnAb epitopes. Autologous neutralizing antibody responses appear upon boosting once immunodominant epitopes are saturated.
View Article and Find Full Text PDFIf a quantum dot is coupled to a topological superconductor via tunneling contacts, each contact hosts a Majorana zero mode in the limit of zero transmission. Close to a resonance and at a finite contact transparency, the resonant level in the quantum dot couples the Majorana modes, but a ground-state degeneracy per fermion parity subspace remains if the number of Majorana modes coupled to the dot is five or larger. Upon varying shape-defining gate voltages while remaining close to resonance, a nontrivial evolution within the degenerate ground-state manifold is achieved.
View Article and Find Full Text PDFLassa fever continues to be a major public health burden in endemic countries in West Africa, yet effective therapies or vaccines are lacking. The isolation of potent and protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccines candidates have generally been unsuccessful in doing so and the associated antibody responses to these vaccines remain poorly characterized.
View Article and Find Full Text PDFBackground: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach.
Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography.
Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct.
View Article and Find Full Text PDFWe predict a novel metallic state of matter that emerges in a Weyl-semimetal superstructure with spatially varying Weyl-node positions. In the new state, the Weyl nodes are stretched into extended, anisotropic Fermi surfaces, which can be understood as being built from Fermi arclike states. This "Fermi-arc metal" exhibits the chiral anomaly of the parental Weyl semimetal.
View Article and Find Full Text PDFUnlabelled: The purpose of this study is to evaluate the influence of the extent of surgery and radiation therapy (RT) on the rates and sites of local (LR) and regional recurrences (RR) in the EORTC 22922/10925 trial.
Patients And Methods: All data were extracted from the trial's individual patients' case report forms (CRF) and analysed with a median follow-up of 15.7 years.
Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap, Solitaire™, and Trevo. We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients.
View Article and Find Full Text PDFThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses.
View Article and Find Full Text PDFHepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine.
View Article and Find Full Text PDFThe Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation.
View Article and Find Full Text PDFProtein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens.
View Article and Find Full Text PDFDelineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.
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