Abstract: The present technology relates to methods, computing devices, and systems for identifying somatic mutational signatures (e.g., cancer, aging) from whole genome sequencing (e.g., low coverage WGS) of cell-free DNA (cfDNA) obtained from subjects. Machine learning techniques may be applied to cfDNA mutational profiles, permitting accurate discrimination between cancer patients and healthy individuals or discrimination between different cancer types.

Abstract: A scoring functions is developed and used for identifying patients who might be responsive to a PD-1 axis directed therapy. The scoring functions are obtained by extracting features from multiplex-stained sections, selecting features that correlate with response to the therapy using a feature selection function, and fitting one or more of the selected features to a plurality of candidate scoring functions. A candidate scoring function showing the desired balance between predictive sensitivity and specificity may then selected for incorporation into a scoring system that includes at least an image analysis system.

Abstract: Disclosed is a method for diagnosing allergy in a human or animal patient, wherein the level of species-specific lipocalin, especially lipocalin 2 in a human patient, is measured in a sample of said patient and wherein a lowered level of said lipocalin compared to the level of said lipocalin in the corresponding sample of a human or animal that has no allergy, is indicative of an allergy, as well as a kit for performing this method, and a kit for quality control of allergen molecules or extracts used for immunotherapy of allergy by determining its siderophore-iron ligand load and thus immunomodulatory potency. Further, lipocalin proteins for use in treatment or prevention of allergies are provided, preferably complexed with siderophore-iron ligands.

Abstract: As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Abstract: The present invention relates to new 1H-pyrazole derivatives of formula (I) as sigma ligands having a great affinity for sigma receptors, especially the sigma-1 receptor (?1) and/or sigma-2 receptor (?2), as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: Apparatus, systems and methods for fracturing calcium in an artery of a patient. Certain embodiments include a diode laser light source and an optical fiber. In particular embodiments, the optical fiber comprises a polymer or glass optical core, a cladding surrounding the polymer or glass optical core. The optical fiber can comprise one or more emission elements configured to emit electromagnetic energy from the laser light source. The electromagnetic energy can be transmitted through a fluid in the expandable member to fracture the calcium.

Abstract: A method of removing impurities using an electrochemical membrane apparatus comprising introducing a leaching solution into an electrochemical membrane reactor. The leaching solution of the electrochemical apparatus comprises copper, aluminum, iron, cobalt, manganese, and nickel. The electrochemical membrane reactor comprises at least one positive electrode and at least one negative electrode, and the leaching solution is in contact with the at least one negative electrode. A current is applied through the electrochemical membrane reactor to adjust a pH of the leaching solution and copper is deposited on the at least one negative electrode. The aluminum and the iron are removed from the leaching solution, and the cobalt, the manganese, and the nickel are recovered from the leaching solution. An electrochemical membrane apparatus including an electrochemical membrane reactor is also disclosed.

Abstract: The present invention relates to new compounds of formula (I) as sigma ligands having a great affinity for sigma receptors, sigma-1 receptor (?1) and/or sigma-2 receptor (?2). The present invention also refers to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: A method of selectively recovering palladium from a palladium-containing material comprises providing a leaching solution comprising hydrochloric acid, hydrogen peroxide, and an iron salt comprising one or both of ferric chloride or ferrous chloride and contacting a palladium-containing material with the leaching solution to dissolve palladium from the palladium-containing material. Related methods of selectively recovering palladium from a palladium-containing material are also disclosed.

Abstract: The present invention relates to new 5,6,7,8-tetrahydropyrido[4?,3?:4,5]thieno[2,3d] pyrimidin-4(3H)-one derivatives as sigma ligands having a great affinity for sigma receptors, especially sigma-1 (?1), as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: The present invention relates to new 2,3-dihydro-1H-pyrrolo[3,2-b]pyridine derivatives of formula (I): as sigma ligands having a great affinity for sigma receptors, especially sigma-1 (?1) and/or sigma-2 (?2) receptors, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

Abstract: Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We generated single chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by human leukocyte antigen (HLA) molecules. These scFvs can be converted to full-length antibodies, termed MANAbodies, targeting “Mutation Associated Neo-Antigens” bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for peptides bound to pre-defined HLA types. In this way, we obtained scFvs, including one specific for a peptide encoded by a common KRAS mutant and another by a common EGFR mutant. Molecules targeting MANA can be developed that specifically react with mutant peptide-HLA complexes even when these peptides differ by only one amino acid from the normal, wild-type form.

Abstract: The present invention relates to pyrazolopyrimidine derivatives having dual pharmacological activity towards both the ?2? subunit of the voltage-gated calcium channel and the sigma-1 (?1) receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Abstract: A method of recovering lithium from a lithium-containing material comprises introducing a lithium-containing material to an electrochemical cell, transporting lithium ions from the lithium-containing material through a cation exchange membrane to a catholyte within a cathode chamber of the electrochemical cell, reacting the lithium ions with bicarbonate ions in the cathode chamber to form lithium carbonate, and removing the lithium carbonate from the catholyte. Related methods of recovering lithium from lithium-containing, materials, and related systems are disclosed.

Abstract: DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.

Abstract: The present disclosure provides compositions comprising dostarlimab and methods of using the same to treat mismatch repair deficient (MMRd) rectal cancer (e.g., locally advanced rectal cancer).

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: Mandibular advancement measurement and positioning device provided with an instrument (1) with an upper slider (2) and a lower slider (3), means to measure and position the relative displacement of both sliders and two trays at one end of the instrument, one upper and one lower (11a, 11b), the trays being attached to each slider respectively, wherein the lower slider is divided into a fixed part (3a) and a pivoting part (3b) joined to the end of the fixed part (3a), being the upper and lower slider joined by means of a recess that allows a relative slide of both and wherein the pivoting part (3b) of the lower slider is provided with a vertical opening control (6). By means of the pivoting part and the opening control it is possible to measure and position the vertical opening.

Abstract: An improved system and method for pouring elevated concrete decking within a frame and backing surface area, wherein deck straps help hold the frame in position relative to the backing surface. The invention involves a bracket stand configured to elevate lower ends of deck straps above the backing surface such that wet concrete can enter the space between the lower end of the deck strap and the backing surface. The bracket stand has a platform elevated by a stable plurality of legs, the tips of which rest on the backing surface. The lower end of the deck strap and bracket stand are secured to the backing surface by one or more fasteners. When the backing surface is removed, a minimal portion of the bracket stand and fasteners is all that might protrude from the underside of the concrete decking. Depending upon the materials, these protruding portions are easily removed.

Abstract: A system and method for collection of a website in a past state and retroactive analysis thereof are provided. The method includes collecting, from a repository, at least one session replay; identifying, in the at least one collected session replay, at least one main state, wherein a main state is a portion of a session replay; selecting at least one webpage snapshot corresponding to a respective main state of the at least one identified main state, wherein each snapshot is a single-instant webpage state at a specific point in time; identifying, in the at least selected one snapshot, at least one webpage zone; and returning the at least one identified zone.