Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.
View Article and Find Full Text PDFObjectives: The attitudes and perceptions of healthcare consumers (HCCs) are increasingly becoming more relevant in decision-making with healthcare providers and incorporated into healthcare decision-making by national immunization technical advisory groups and health technology assessment agencies. With newer pneumococcal vaccine options available, HCCs' attitudes and perceptions play a key role in gauging potential acceptance. The objective of this study was to assess HCCs' knowledge, attitudes, and perceptions toward pneumococcal vaccines for adults.
View Article and Find Full Text PDFThe human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.
View Article and Find Full Text PDFNat Rev Clin Oncol
December 2024
Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.
View Article and Find Full Text PDFHemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163.
View Article and Find Full Text PDFBackground: Novel, expanded valency pneumococcal conjugate vaccines (PCVs) are in development to reduce the burden of pneumococcal disease (PD) in children. To understand the potential value of new vaccines in Germany, this study estimated the residual burden of PD in children < 16 years old from 2014 to 2019, using administrative health data from a large German claims database.
Methods: Outpatient and inpatient cases of all-cause pneumonia (ACP), pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) were identified in the InGef database.
Human milk oligosaccharides are of high interest as active ingredients in infant formulas and dietary food supplements. Full characterization of members of this compound class is challenging due to the intrinsic complexity of byproducts during synthesis by fermentation. Moreover, when method validation is targeted for a regulated environment, a robust chromatographic separation of the highly polar oligosaccharides needs to be addressed, including isomers and compounds relevant for potential product adulteration.
View Article and Find Full Text PDFBackground: Multicomponent improvement (MCI) is a novel endpoint for predicting survival in patients with pulmonary arterial hypertension (PAH), included in the sotatercept clinical program. For the first time, we investigated the prognostic value of MCI, ESC/ERS 4-strata risk (4SR) assessment, and the non-invasive French risk stratification score (FRS), for predicting survival in PAH patients in Sweden. All risk prediction models are based on three parameters: WHO-FC (World Health Organization Functional Class), NT-proBNP, and 6MWD (6-minute walk distance).
View Article and Find Full Text PDFA significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which is densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint therapy targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy is associated with toxicity and low bioavailability in solid tumors. In this work, we engineer a CAR T cell against epidermal growth factor receptor variant III (EGFRvIII), constitutively secreting a signal regulatory protein gamma-related protein (SGRP) with high affinity to CD47.
View Article and Find Full Text PDFBackground/objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages.
View Article and Find Full Text PDFElucidating the interactions that drive antigen recognition is central to understanding antibody-mediated protection and is vital for the rational design of immunogens. Often, structural knowledge of epitopes targeted by antibodies is derived from isolated studies of monoclonal antibodies, for which numerous structural techniques exist. In contrast, there are very few approaches capable of mapping the full scope of antigen surfaces targeted by polyclonal sera through the course of a natural antibody response.
View Article and Find Full Text PDFObjectives: It is important to assess healthcare providers (HCPs) knowledge, attitudes, perceptions, and preferences towards new pneumococcal vaccines for adults.
Methods: HCPs who met eligibility criteria completed an online survey between March - May 2024 that included a discrete choice experiment (DCE) to elicit preferences.
Results: Among 340 participating HCPs, the average age was 44.
Multiple species of frogs in the Ranidae family have been observed to 'skitter' across the water surface, but little is understood about the biomechanical or physical mechanisms that underlie this behavior. All documented descriptions are anecdotal, asserting simply that the frogs can cross the water surface without sinking. To study this form of interfacial locomotion, we recorded high-speed video of the northern cricket frog Acris crepitans and quantified its kinematics.
View Article and Find Full Text PDFThe field of photonic integrated circuits has witnessed significant progress in recent years, with a growing demand for devices that offer high-performance reconfigurability. Due to the inability of conventional tunable directional couplers (TDCs) to maintain a fixed phase while tuning the reflectivity, Mach-Zehnder interferometers (MZIs) are employed as the primary building blocks for reflectivity tuning in constructing large-scale circuits. However, MZIs are prone to fabrication errors due to the need for perfect balanced directional couplers to achieve 0-1 reflectivity, which hinders their scalability.
View Article and Find Full Text PDFThe mechanisms underlying the remarkable capacity of the liver to regenerate are still not completely understood. Particularly, the cross-talk between cytokines and cellular components of the process is of utmost importance because they represent potential avenues for diagnostics and therapeutics. WNT1-inducible-signaling pathway protein 1 (WISP1) is a cytokine member of the CCN family, a family of proteins that play many different roles in liver pathophysiology.
View Article and Find Full Text PDFBackground: We aim to investigate the impact of routine cholangiography on asymptomatic patients with percutaneous cholecystostomy (PCC) for acute cholecystitis (AC).
Methods: The study included all patients treated with PCC for AC from 2017 to 2020 at a single academic center. Patients who underwent routine cholangiography within 30 days post-discharge while asymptomatic were compared to patients who were only followed clinically.