Abstract: The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention.

Abstract: The invention relates to a molecular scaffold suitable for covalently binding at least one biologically active molecule to a carrier molecule, the scaffold comprising a polymeric structure and the biologically active molecules covalently bound to said polymeric structure, and wherein the scaffold further comprises a chemical group for covalently coupling of the scaffold to the carrier molecule. The biologically active molecule has a molecular weight of 3.000 Dalton or less, such as 1.700 Dalton-1.950 Dalton. The biologically active molecule is an amphiphilic molecule in some embodiments. The biologically active molecule is a single specific molecule or is a mixture of different types of molecules, when more than one biologically active molecules are covalently bound to the polymeric (or oligomeric) structure. In particular, the invention relates to monoclonal antibody-based antibody-drug conjugates with improved therapeutic window of the drug due to covalent linkage of (a cluster of) potentiator molecules, e.

Abstract: The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention.

Abstract: The current invention relates to an effector moiety capable of inducing an intracellular effect when present inside a mammalian cell, the effector moiety comprising a payload conjugated with at least one saponin. The invention also relates to an antibody-drug conjugate comprising the effector moiety according to the invention, or a ligand-drug conjugate comprising the effector moiety of the invention, the effector moiety comprising covalently coupled saponin. The invention also relates to a therapeutic combination comprising: (a) the effector moiety of the invention, comprising at least one saponin, and optionally a pharmaceutically acceptable excipient; and (b) an antibody-drug conjugate or a ligand-drug conjugate, and optionally a pharmaceutically acceptable excipient.

Abstract: The present invention relates to the field of biomaterials, more particularly to the field of poly(alkyl cyanoacrylate) based nano- and microfibers. The present invention provides a novel method for producing ready-to-use poly(alkyl cyanoacrylate) based nano/microfibers, wherein the method comprises electrospinning of poly(alkyl cyanoacrylate) homopolymers or copolymers generated by anionic polymerization of alkyl cyanoacrylate monomers or oligomers and characterized by a specific polydispersity index. Accordingly, the present invention also provides novel ready-to-use nano/microfibers obtainable by the method as well as uses thereof, including (therapeutic) biomedical applications such as wound healing, drug delivery and tissue regeneration and engineering.

Abstract: The present invention relates to a method for preserving urinary cells, the method comprising the step of contacting a urine sample obtained from a patient with a buffer substance suitable to create and/or maintain a pH value in the range of 6 to 8, particularly approx. 7, within said urine sample, and a formaldehyde releasing compound.

Abstract: The present invention provides methods and compositions for promoting regeneration of a tissue, methods for preventing or reducing inflammation of a tissue, methods for preventing or reducing fibrosis of a tissue, methods for increasing a mass of a tissue, methods for increasing a level of oxygen available to a tissue, methods for increasing a rate of metabolic waste removal from a tissue, methods for increasing blood perfusion to a tissue, and methods of treating severe muscle tissue damage in a subject in need thereof by contacting the tissue with a composition that is suitable for applying cyclic mechanical compression to the tissue.

Abstract: The invention relates to a method and a computer program for automatic shape quantification of an optic nerve head from three-dimensional image data (1) acquired with optical coherence tomography, comprising the steps of: a) Providing (100) three-dimensional image data (1) of the retina, the image data comprising at least a portion of the optic nerve head, wherein the image data comprises pixels with associated pixel values; b) In the three-dimensional image data (1) identifying (200, 300) anatomic portions of the optic nerve head, the anatomic portions comprising a retinal pigment epithelium (RPE) portion (3) and an inner limiting membrane (ILM) portion (2); c) Determining an RPE polygon mesh (30) for a lower boundary of the retinal pigment epithelium portion (3), wherein the RPE polygon mesh (30) extends along the lower boundary of the retinal pigment epithelium portion (3); d) Determining an ILM polygon mesh (20) for the inner limiting membrane portion (2), wherein the ILM polygon mesh (20) extends alon

Abstract: The invention relates to a method for determining T cell mediated immunity towards a CRISPR associated protein by contacting said cell preparation obtained from a patient with a CRISPR associated protein or a peptide mix that represents its amino acid sequence, or a cell manipulated to contain a CRISPR protein polypeptide to provide activated T cells. Subsequently, one or more subpopulations of said activated T cells are marked by specific ligand and counted, and a ratio (TREG/TEFF) of activated regulatory T cells to activated effector T cells is used to assess the immune status of the patient with respect to the CRISPR associated protein. The invention further relates to a method for generating a CRISPR associated protein specific Treg population and its use in therapy.

Abstract: Described herein is the use of a uromodulin polypeptide in prevention or therapy of vascular calcification or a disease caused by, or related to, vascular calcification, particularly vascular calcification in chronic kidney disease, in diabetes, in aging and in atherosclerosis.

Abstract: The invention relates to a method and a computer program for segmentation of optical coherence tomography images of the retina comprising the steps of: a) Acquiring image data comprising a portion of the vitreous and a portion of the retina recorded with optical coherence tomography, wherein the portion of the retina comprises at least a portion of the optical nerve head, wherein the image data comprises pixels with associated pixel values; b) Providing a contour with a predefined initial shape and an initial position on the image data; c) Adjusting the shape and/or the position of the contour on the image data such that the adjusted contour separates the image data in a first region comprising the vitreous and a region comprising the retina, wherein the shape and position of the contour is adjusted with an optimization method, d) wherein the optimization method minimizes a contour-associated energy that depends on the contour shape, the contour position and the image data, wherein the contour-associated ener

Abstract: The present disclosure relates to a hemodialysis membrane for the treatment of vascular calcification in hemodialysis patients, especially in chronic hemodialysis patients. The present disclosure further relates to methods of treating vascular calcification in hemodialysis patients, wherein the hemodialysis membrane is characterized in that it comprises at least one hydrophobic polymer and at least one hydrophilic polymer and in that it has a MWRO of between 15 and 20 kD and a MWCO of between 170-320 kD or that the hemodialysis membrane comprises at least one hydrophobic polymer and at least one hydrophilic polymer and has a MWRO of between 8.5 kD and 14.0 kD and a MWCO of between 55 kD and 130 kD.

Abstract: A method diagnoses a SARS-CoV-2 infection and includes detecting the presence or absence of an antibody to SEQ ID NO: 1, preferably IgA class antibody, in a sample from a subject. A method differentially diagnoses a coronavirus infection. An antibody to SEQ ID NO: 1, preferably IgA class antibody, is used for diagnosing a SARS-CoV-2 infection or for the differential diagnosis of a coronavirus infection, preferably for distinguishing between a SARS-CoV-2, MERS and NL63, 229E, OC43 and HKU1 infection. A kit includes a polypeptide comprising SEQ ID NO: 1 or a variant thereof, preferably coated to a diagnostically useful carrier and one or more of the following reagents: an antibody to SEQ ID NO: 1, a washing buffer, a means for detecting the presence of an antibody, preferably IgA class antibody, preferably a secondary antibody binding specifically to IgA class antibodies, preferably comprising a detectable label, and a dilution buffer.

Abstract: Disclosed herein are methods, devices and kits suitable for high throughput screenings of extracellular pyridine nucleotide levels, such as NAD+ levels which are suitable for monitoring pyridine nucleotide induced slowdown of not only pathogenesis of multiple systemic diseases but also aging. In particular, assaying methods quantifying extracellular pyridine nucleotide(s), such as NAD+, in the low micromolar to the low nanomolar range in a sample that may have been subjected to long term storage are disclosed using a two-step enzymatic cycling reaction employing an oxidoreductase such as alcohol dehydrogenase. A modified revised simulated body fluid is also disclosed that is employed as a standard matrix to optimise enzymatic activity, linearity and/or sensitivity of the methods, devices and kits.

Abstract: The present invention pertains to antigen recognizing constructs against tumor specific proteasome splicing variants. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for tumor cells carrying antigenic epitopes generated by proteasome peptide splicing of tumor specific antigens. The TCRs of the invention, and antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of proliferative diseases, preferably for the treatment of cancer. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: The present invention relates to a compound for use in a method for treating a musculoskeletal injury, wherein the compound is a regulator of the pro-inflammatory response and particularly being capable of upregulating regulatory T cells and/or M2-macrophages; and/or being capable of downregulating the biological activity of effector CD8+ cells, and further comprising the dosage regimen administering an initial dose of said compound to a patient not before 24 hours after said musculoskeletal injury.

Abstract: The present invention relates to a method for predicting the probability of having or developing a non-fusion, wherein said method comprises determining the frequency of a subpopulation of CD8+ T cells selected from CD8+CD57+, CD8+CD28? and CD8+CD57+CD28? in a sample obtained from a patient. The invention further relates to a system for predicting the probability of having or developing a non-fusion.

Abstract: A biomaterial, particularly for tissue regeneration, includes an open, porous bioresorbable first material portion and a second material portion that is stiffer than the first material portion, wherein the volume fraction of the stiffer material is less than 30% of the total volume of the biomaterial, and the structural stiffness of the second material portion is at least 10 times greater than that of the first material portion.

Abstract: The invention relates to a method and a computer program for estimating shape parameters of an image data set (1) of a fovea (100), comprising the steps of: Acquiring an image data set (1) of a macula (50), comprising a foveal pit (101) and a foveal rim (102) at least partially, Estimating the center of the foveal pit (101) from the image data set (1), Estimating from the center of the foveal pit (101), radially extending height profiles (c) of the fovea (100), For each height profile (c), fitting a model-function to the height profile (c), Estimating for each height profile (c) a set of fit parameters from the fitted model-function, Determining from the sets of estimated fit parameters at least one shape parameter of the fovea (100), particularly of the foveal pit (101). Determining at least one shape feature of at least a part of the fovea.

Abstract: The invention includes a substance based on nanocrystalline maghemite having a crystal size of between 0.5 and 4 nm, which is defined by a proportion of divalent iron ions less than five percent by weight of the total iron, and the transport of sodium and simultaneously phosphate in the gastrointestinal wall from the gastrointestinal contents into the bloodstream is reduced and thus can improve the imbalance of electrolyte and water and mineral balances of patients having impaired renal function when used orally in combination with suitable pharmaceutical adjuvants.