The collecting and storing of human biospecimens and associated data are a historical fact in medicine, but the biobank is a very recent concept. The advent of new technologies making it possible to ...store all types of specimens, including cells capable of staying alive outside the human body for an indefinite length of time, and to obtain scientific data of all types, including genetic information, has opened up a whole new realm of possibilities for research. All of the above has led to complex ethical issues coming to fore concerning the specimen donors, the researchers handling the specimens and society as a whole. This document is aimed at providing some recommendations to serve as a guideline and encourage responsible deliberation among all those involved, thus contributing to society's recognition and trust in the forthrightness of the research and the solidary end purposes thereof. A total of nineteen recommendations have been drafted concerning the following aspects: Biobank organization and operation, degree of specimen identification, data management guarantees, consent for taking part in research and for the incorporation of specimens into the biobank, the right to know and the right not to know, consent for transferring specimens to third parties, specimen harvesting in deceased individuals, management of the pre-existing biospecimen collections, title to and commercialization of specimens and research findings and resulting payback benefiting the community.
The aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13.
250 consecutive patients with rheumatic diseases ...under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied.
50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed.
Anti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.
Current models of the TCR / CD3 complex assume that, in mature peripheral T lymphocytes, variability is restricted to the α β (or γ δ) chains of the TCR heterodimer responsible for antigen ...recognition, whereas the CD3 polypeptides involved in signal transmission are invariant. Here we show that mouse CD4+ T lymphocytes and T cell lines are bound with different avidity by anti‐CD3 monoclonal antibodies. These findings cannot be accounted for by allelic differences between CD3 chains, by the nature of the TCR chains, or by the ratio of CD3ϵ δ to CD3ϵ γ chain pairing. Rather, they are linked to heterogeneity of the N‐terminal region of CD3ϵ chains, as detected by peptide‐specific antibodies. In turn, these differences among CD3ϵ chains correlate with variations in the strength of TCR / CD3 interaction. N‐terminal CD3ϵ heterogeneity is not due to alternative splicing mechanisms, but rather involves digestion by metalloproteases, as suggested by reverse transcription‐PCR amplification and by the effect of protease inhibitors, respectively. Based on these data, we propose a model linking CD3ϵ N‐terminal variability with altered CD3 recognition by monoclonal antibodies and TCR / CD3 interaction. This model suggests the possibility of distinct spatial arrangements of the TCR / CD3 complex.
•Surfaces in which chitosan domains with antibacterial properties alternate with titanium domains.•Chitosan is hosted in microgrooves practiced in the titanium surface.•MC3T3-E1 pre-osteoblasts ...preferentially adhered on the titanium regions whereas C2C12 myoblasts distributed uniformly throughout the whole surface.
Titanium and its alloys are widely used in medical implants because of their excellent properties. However, bacterial infection is a frequent cause of titanium-based implant failure and also compromises its osseointegration. In this study, we report a new simple method of providing titanium surfaces with antibacterial properties by alternating antibacterial chitosan domains with titanium domains in the micrometric scale. Surface microgrooves were etched on pure titanium disks at intervals of 60μm using a modified 3D printer and were then coated with chitosan antibacterial polysaccharide. The dimensions of the patterned microgrooves made it possible to fix the chitosan domains to the titanium substrate without the need for covalent bonding. These domains were stable after 5days of immersion in water and reduced the surface contact angle. Preliminary cell adhesion assays demonstrated that MC3T3-E1 pre-osteoblasts preferentially adhered to the titanium regions, while C2C12 myoblasts were uniformly distributed over the whole surface.
A relationship among April births, HLA-DRB1*15:01 genotype and risk of multiple sclerosis (MS) has been described. We aim to determine this association in our cohort of Spanish MS patients.
We ...genotyped HLA-DRB1*15:01 allele in 326 MS patients and 226 controls (non-neurological disease patients) by SSP-PCR and compared month of birth with local births during the same period.
MS patients carrying HLA-DRB1*15 allele were more frequently born in December (10.3% HLA-DRB1*15+ vs. 3.8% HLA-DRB1*15-; p = 0.019). Controls carrying HLA-DRB1*15 allele were less frequently born in December than non-carrier controls (0% HLA-DRB1*15+ vs. 10.3% HLA-DRB1*15-; p = 0.028). Thus, December was confirmed as the common month of birth for HLA-DRB1*15-non-carrier controls and MS HLA-DRB1*15-carrier patients.
Month of birth, HLA-DRB1 genotype and risk of MS are associated. In Spain, this association was found in December, supporting the potential interaction of a seasonal risk factor in winter, inside/close to HLA-DRB1*15 locus, during pregnancy or after birth.
Modeling of the 3D Tree Skeleton Using Real-World Data: A Survey Cardenas, Jose L.; Ogayar, Carlos J.; Feito, Francisco R. ...
IEEE transactions on visualization and computer graphics,
2023-Dec., 2023-12-00, 20231201, Letnik:
29, Številka:
12
Journal Article
Recenzirano
Tree modeling has been extensively studied in computer graphics. Recent advances in the development of high-resolution sensors and data processing techniques are extremely useful for collecting 3D ...datasets of real-world trees and generating increasingly plausible branching structures. The wide availability of versatile acquisition platforms allows us to capture multi-view images and scanned data that can be used for guided 3D tree modeling. In this paper, we carry out a comprehensive review of the state-of-the-art methods for the 3D modeling of botanical tree geometry by taking input data from real scenarios. A wide range of studies has been proposed following different approaches. The most relevant contributions are summarized and classified into three categories: (1) procedural reconstruction, (2) geometry-based extraction, and (3) image-based modeling. In addition, we describe other approaches focused on the reconstruction process by adding additional features to achieve a realistic appearance of the tree models. Thus, we provide an overview of the most effective procedures to assist researchers in the photorealistic modeling of trees in geometry and appearance. The article concludes with remarks and trends for promising research opportunities in 3D tree modeling using real-world data.
The role of membrane cofactor protein (MCP, CD46) on human T cell activation has been analyzed. Coligation of CD3 and CD46 in the presence of PMA or CD28 costimuli enhanced IL-2, IFN- gamma , or ...IL-10 secretion by CD4 super(+) T lymphocytes. The effect of CD46 on IL-10 secretion did not require additional costimuli like anti-CD28 antibodies or phorbol esters. CD46 also enhanced IL-2 or IFN- gamma secretion by CD4 super(+) blasts. In contrast, IL-5 secretion was inhibited upon CD46-CD3 coligation, in all the cells analyzed. These effects were independent of IL-12 and suggest that CD46 costimulation promotes a Th1- biased response in human CD4 super(+) T lymphocytes. CD46 enhanced TCR/CD3-induced tyrosine phosphorylation of CD3 direct sum and ZAP-70, as well as the activation of the ERK, JNK, and p38, but did not modify intracellular calcium. The effect of specific inhibitors shows that enhanced ERK activation contributes to augmented IFN- gamma and lower IL-5 secretion and, consequently, to the Th1 bias. Cross- linking CD46 alone induced weak tyrosine phosphorylation of CD3 direct sum and ZAP-70. However, CD46 cross-linking by itself did not induce cell proliferation or lymphokine secretion, and pretreatment of CD4 super(+) T lymphocytes with anti-CD46 antibodies did not significantly alter TCR/CD3 activation.
Tyrosine phosphorylation of different substrates is the earliest intracellular signal detected after T cell receptor (TcR) ligation. Several tyrosine kinases have been detected associated to the ...CD3-TcR complex in stimulated or unstimulated cells, including p56lck, p59fyn and ZAP-70. We have observed, in one mouse T helper CD4 T cell line, that most TcR- or CD3-associated tyrosine kinase activity comes from CD4:p56lck (Diez-Orejas, R., Ballester, S., Feito, M. J., Ronda, M., Ojeda, G., Criado, G., Portolés, P. and Rojo, J. M., EMBO J. 1994. 13: 90). To analyze whether this is a major way of tyrosine kinase association to the TcR in normal CD4+ T cells, we examined the nature and mode of association of tyrosine kinases to the TcR complex in normal spleen CD4+ T lymphocytes. Our results show that, in normal CD4+ T lymphocytes, as in CD4+ T cell lines, there is a stable and readily detectable association between CD4:p56lck and the TcR/CD3 complex, as determined by in vitro kinase activity in immunoprecipitates from cell lysates. However, TcR/CD3 complexes from nature CD4+ lymphocytes have detectable amounts of p56lck associated in a CD4-independent manner, as shown by immunodepletion of the lysates with anti-CD4 antibodies. In addition, TcR/CD3 also bind p59fyn regardless of the presence of CD4. Conversely, we have observed that CD4 co-precipitates small quantities of p56fyn in a TcR/CD3-independent manner. Overall, our data suggest the existence of different possible molecular complexes between TcR/CD3, CD4 and their attending kinases, as well as some quantitative and qualitative differences between CD4+ T cells and CD4+ T cell lines in kinase association to the TcR/CD3 complex.
Laminate composite materials such as CFRPs are highly susceptible to delamination, being one of the common failure modes in composite laminates. The combination of severe delamination with uniaxial ...compressive loads leads to the loss of stability and structure failure. In this study, the authors present an experimental and numerical analysis of this effect in laminates. A series of tests were carried out with four different specimens including delamination-free plates and plates with incipient delamination with different damage size and location. 3D Digital Imagen Correlation technique was applied to predict the buckling initiation and propagation and to validate the numerical models implemented, showing good agreement between the numerical and experimental results. Model material failure includes Hashin criterion and cohesive zone model (CZM) to predict delamination. Finally, numerical models have been used to predict the crack initiation and progression in the rest of samples.
Background
Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital ...presentation.
Objectives
We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions.
Methods
We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14‐year period. Histopathology and immunohistochemistry studies were performed.
Results
Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three‐quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started.
Limitations
Data were collected retrospectively.
Conclusions
Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early.