A bioink for cryobioprinting is described. The bioink comprises a decellularized extracellular matrix (dECM)-based hydrogel and a saccharide cryoprotectant. A method of making a 3D-printed biomaterial is also described, which includes depositing a bioink comprising a dECM-based hydrogel, cells, and a saccharide cryoprotectant from a 3D printer onto a freezing plate to form a frozen bioink filament; depositing additional bioink from a 3D printer in contact with a previously placed frozen bioink filament to form a 3D-printed biomaterial comprising a plurality of frozen bioink filaments; and removing the 3D-printed biomaterial from the freezing plate. 3D-printed biomaterials made according to the method are also described.
Smart needle systems and related methods, such as smart injection needle system for accurate characterization of cell types, concentrations, and viability, are generally provided. In some embodiments, fluidic components (e.g., configured to interface with a medical device such as a syringe or in-line flow system) are provided.
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
3.
COMPOSITIONS, SYSTEMS AND METHODS RELATING TO THE IDENTIFICATION OF HLA CLASS II-BINDING PEPTIDES
The technology described herein is directed to compositions and methods for generating synthetic antigen presenting cells (APCs) that express a single HLA-II allotype and key genes for HLA-II processing and presentation, and express no other HLA-II allele. Further disclosed are systems and methods of using the synthetic APCs for identifying allele-specific HLA Class II (HLA-II) peptides using genetic screening.
The disclosure provides compositions and methods for treating inflammatory bowel disease (IBD) by inhibiting signaling molecules of the IL1 signaling pathway. Specifically, methods for treating IBD are provided, the methods comprising administering to subjects having IBD inhibitors of IL1 receptor 1 (IL1R1), inhibitors of transcription factors MEOX1 and MAFF to block MEOX1 and MAFF signaling in intestinal stroma cells.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
5.
LUMINESCENCE CASCADE SENSOR FOR POINT-OF-CARE PATHOGEN DETECTION
22, yielding oxyluciferin and luminescence. Repeated catalytic cycles increase a measurable signal of the luminescence. An optical sensor can capture an image of the luminescence and the presence of tagged target components can be determined based on an amount of luminescence in the image.
C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving luciferase
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
Stabilized forms of Gal-1, and a method of treating infection by S. pneumoniae in a subject, comprising administering a therapeutically effective amount of a Gal-1 polypeptide or modified Gal-1 polypeptide to the subject, are described.
The present disclosure describes microneedle array compositions comprising a plurality of microneedles projecting from a substrate. Each microneedle of the plurality of microneedles comprises a penetrating tip and a base that is integrally connected with the substrate, wherein each microneedle of the plurality of microneedles is a porous microneedle composed of a degradable hyaluronic acid polymer comprising a disulfide bond coupled to a terminal amine group. Each microneedle of the plurality of microneedles comprises one or more lipid nanoparticles comprising: an amount of an ionizable lipid, an amount of a neutral lipid, an amount of cholesterol, an amount of one or more polyethylene glycol lipids (PEG-lipids), and an amount of a N-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium (DOTAP) molecule.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/1271 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
A61K 9/1272 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61M 5/162 - Needle sets, i.e. connections by puncture between reservoir and tube
Methods of assessing a biological sample, a system, a kit, and a computer readable storage media are provided herewith. Some of the methods include determining, in the biological sample, a concentration for protein biomarkers; analyzing the concentrations of the at biomarkers using a trained biomarker model that has been trained to discriminate between cancer samples and benign samples; and providing the model output for the assessment of a cancer. Some of the methods include assisting in the diagnosis of a breast cancer.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
An organ-on-a-chip (OoC) platform can link one or more OoC modules in parallel, mimicking oxygen levels of cultures with biological materials housed therein in each OoC module. Each OoC module can include an oxygen sensor; an oxygen scavenger to decrease an oxygen level within the culture medium surrounding the at least one type of biological material. Each OoC module can be connected to a controller, the controller comprising: a memory storing instructions; and a processor configured to access the memory to execute the instructions to at least: for each of the at least one OoC module, ensure that the oxygen level of the culture medium surrounding the at least one type of biological material is physiological based on control of the oxygen scavenger.
Method and system for generating predicted trajectories for navigating a catheter through a lumen, the system including: a steerable catheter including a proximal end, a distal end, a catheter tip, and a tool channel extending from the proximal end to the distal end; an imaging device disposed within the steerable catheter; a console including a system controller, a display controller, and a display; and a navigation module configured to: receive preoperative data and multiple consecutive images from the imaging device from the system controller, and output information based on the received preoperative data and the multiple consecutive images, the information including at least one of: a location, a direction, or a recommended trajectory for navigating the catheter through the lumen.
A61M 25/01 - Introducing, guiding, advancing, emplacing or holding catheters
A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
A61B 34/00 - Computer-aided surgeryManipulators or robots specially adapted for use in surgery
The present disclosure relates to generally to methods of ameliorating or treating the neurological effects of microglial activation and methods of ameliorating or treating specific diseases that affect the central nervous system (CNS) by administering an anti-CD3 antibody in combination with a GLP-1 agonist.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
System configured to facilitate locomotion at a location internal to a subject are generally presented. In some embodiments, the present invention generally relates to enteroscopic robots and related methods, such as bioinspired soft enteroscopic robots for facilitating locomotion, steering, and intervention in the small intestine. In some embodiments, the system comprises a flexible linear actuator, a first expandable actuator operably linked to the first end of the flexible linear actuator, and a second expandable actuator operably linked to the second end of the flexible linear actuator. In some embodiments, the system enables the delivery of one or more tools, one or more pharmaceutical agents, and/or one or more electronic components to a location internal to the subject (e.g., the small intestine).
Described herein are multiplex single molecule assays for ultrasensitive detection of biomolecules, based on an ultrasensitive multiplex digital ELISA platform that substantially reduces cross-reactivity, and methods of use thereof.
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
14.
TARGETING THE RHOA SIGNALING PATHWAY TO CORRECT DISRUPTED RETROMER-DEPENDENT TRAFFICKING
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
15.
ARTICLES FOR UNDERWATER ADHESION FOR SOFT SUBSTRATES
Embodiments described herein generally relate to bio-inspired articles for underwater adhesion for soft substrates and related methods. In some embodiments, an article configured for underwater adhesion to soft substrates is provided. In some embodiments, the article comprises: an adhesive disk, comprising: an elastomeric compartment; and a plurality of tilt-angled lamellae structures, wherein each adhesive compartment is configured to separately seal lamellae pairs for hydrostatic differentiation. In some embodiments, the article further comprises a backbone support structure. In some embodiments, the article further comprises a pharmaceutical agent (e.g., drug delivery polymer matrix, microneedles), electronic component (e.g., RFID), and/or biochemical sensor (e.g., impedance sensor) associated with the disk. In some embodiments, the tilt-angled lamellae have an angle of greater than or equal to 0 degrees and less than or equal to 60 degrees. In some embodiments, the underwater adhesion of the article does not require the external application of vacuum pressure.
The disclosure relates, in various embodiments, to devices, articles, and methods for jetting an active pharmaceutical ingredient into a patient using an electrically-triggered microactuator powered by a reactive material such as an aluminium-nickel nanofilm.
The present disclosure relates, in various aspects, to devices comprising biodegradable (e.g., bioresorbable) RFID antennas and dissolvable coatings. By employing fully biodegradable materials, the devices provided herein may obviate the need for device retrieval or battery replacement, thereby mitigating electronic waste. Moreover, the tags were compatible with standard gelatin or hydroxypropyl methylcellulose (HPMC) capsules, further enhancing clinical translational potential.
A method includes receiving MR data for a subject, generating a map of atrophy coordinates for the subject using a set of volumetric MR data from the MR data, defining a plurality of regions of interest (ROIs) for the subject based on the atrophy coordinates in the map of atrophy coordinates, generating a connectivity map for each ROI using a set of functional connectivity data from the MR data, retrieving a unified schizophrenia network connectivity map of atrophy patterns, determining a probability of progression to schizophrenia for the subject based on the connectivity map for each ROI and the unified schizophrenia network connectivity map of atrophy patterns, and generating a report including at least the probability of progression to schizophrenia for the subject. The method can further include identifying target(s) for a proactive intervention for the subject based on the connectivity maps for each ROI.
G16H 15/00 - ICT specially adapted for medical reports, e.g. generation or transmission thereof
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
19.
RANKING OF REPRODUCTIVE CELLULAR STRUCTURES USING MULTIPLE INSTANCE LEARNING
Systems and methods are provided for a method is provided for ranking a cohort of reproductive cellular structures. A set of images, each representing a reproductive cellular structure of the cohort of reproductive cellular structures, is provided to a predictive model utilizing an attention mechanism to provide an output representing a likelihood of a successful outcome associated with the cohort of reproductive cellular structures. The predictive model is trained using multiple instance learning on a set of training samples, with each training sample including a set of images representing a set of reproductive cellular structures and a value representing an outcome associated with the set of reproductive cellular structures. A total attention associated with each of the set of images at the predictive model is determined. The cohort of reproductive cellular structures is ranked according to the total attention associated with each of the set of images.
G06V 10/77 - Processing image or video features in feature spacesArrangements for image or video recognition or understanding using pattern recognition or machine learning using data integration or data reduction, e.g. principal component analysis [PCA] or independent component analysis [ICA] or self-organising maps [SOM]Blind source separation
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
20.
OLIGOMER-INDUCED RECONSTITUTION OF BIOLUMINESCENCE SENSORS FOR MULTIPLEX DETECTION OF ANALYTES
Described herein are fusion proteins and methods of using those fusion proteins for the detection and identification of analytes (e.g., multimeric proteins expressed by pathogenic organisms or mammalian cells). In some embodiments, it includes a plurality of pairs of fusion proteins distinct for one analyte wherein each pair comprises i) a first fusion protein comprising one or more binding domains fused to a first portion of a reporter protein, and ii) a second fusion protein comprising one or more binding domains fused to a second portion of the same reporter protein, wherein the first and second portions of the reporter protein, when together, comprise the reporter protein in its entirety and restore its function, wherein the first fusion protein and/or the second fusion protein further comprises a fluorophore, and wherein the fluorophore for each pair has a distinguishable emission spectrum.
C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving luciferase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
22.
A CIRCULAR ENGINEERED SORTASE FOR INTERROGATING H3 HISTONE IN CHROMATIN
Discussed herein are novel engineered polypeptides which are effective at cutting and tagging H3 histone tails from endogenous histones, facilitating multiplex "cut-and-paste" middle down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of H3 histone modification crosstalk after treatment with different histone deacetylase inhibitors.
The technology described herein is directed to devices, systems, kits, and methods relating to detecting the contents and characteristics of a fluid in a medical drain.
A61M 27/00 - Drainage appliances for wounds, or the like
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
Tissue oxygenation compositions comprising a hydrogel and an oxygen carrier compound are described. Tissue oxygenation precursor compositions and methods of using tissue oxygenation compositions for tissue oxygenation are also described.
Systems and methods are provided for decision support in toxicology assessment. The system includes a processor and a non-transitory computer readable medium storing instructions executable by the processor to provide an imager interface that receives an image of organ tissue of an animal and a vision encoder trained on a plurality of training images that receives the image of organ tissue and provides a representation of the image of organ tissue. Each training image includes an image of organ tissue of an animal. A toxicology front end generates one of a value representing lesions within the image of organ tissue or an image having a similar representation from the representation of the image of organ tissue.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
G16H 15/00 - ICT specially adapted for medical reports, e.g. generation or transmission thereof
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
A61P 37/00 - Drugs for immunological or allergic disorders
Systems and methods for simulating a CBCT scan implement or include receiving a set of initial CBCT scan parameters; generating a mono-energetic simulation of the CBCT scan using the initial CBCT scan parameters; storing a slice of the mono-energetic simulation in memory; receiving a set of updated CBCT scan parameters; and modifying the stored slice of the mono-energetic simulation based on the updated CBCT scan parameters.
in silicoin silico protein evolution, surpassing current state-of-the-art methods and yielding proteins with more than 100-fold improvement of desired properties. EVOLVE-Pro demonstrates the necessity for protein engineering models to zoom in on desired functional properties rather than predicted fitness, paving the way for broader applications of AI-guided protein engineering in biology and medicine.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/01 - Preparation of mutants without inserting foreign genetic material thereinScreening processes therefor
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Described herein are compositions, kits, and methods for chromatin accessibility measurement using genome editing by double-stranded DNA cytosine deaminases (Ddds).
Formulations for stabilizing Lactobacillus and Bifidobacterium strains are provided, comprising one or more excipient selected from the group consisting of D-(-)-fructose, Bacto Tryptic Soy Broth (BTSB), potassium gluconate, magnesium D-gluconate, sucrose, and/or maltodextrin, and preferably also comprising L-histidine, as are lyophilized cell populations generated using the formulations, and the use of such lyophilized cell populations.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
BRIGHAM AND WOMEN'S HOSPITAL, INC. (USA)
Inventor
Marassi, Francesca M.
Schifferli, Dieter M.
Waldor, Matthew Kaden
Dehinwal, Ruchika
Abstract
Salmonella entericaSalmonella enterica serovar Typhimurium protein PagC or a functional portion thereof. Methods of expressing the engineered outer membrane proteins in a cell, such as a Gram-negative bacteria, to increase the production of outer membrane vesicles are also provided.
Various examples include microfluidic devices or a microphysiological analysis platform (MAP) device. One example MAP device includes a set of arrays. An array of the set of arrays includes a set of chambers configured to contain a set of three-dimensional (3D) tissues. A chamber of the set of chambers is configured to contain a 3D tissue of the set of 3D tissues. The array also includes a perfusion system configured to exchange fluid with the set of chambers. The perfusion system facilitates uniform development of the set of 3D tissues. The array additionally includes a set of electrodes. A subset of the set of electrodes is configured to perform non-contact monitoring of electrophysiological signals in the organoid. The example MAP device also includes a flow control component configured to control the flow of fluid through the perfusion system.
Provided herein are materials and methods for determining responsiveness of any therapy that enhances regulatory T cell (Treg) function in the treatment of inflammatory bowel disease (IBD). The materials and methods provided herein may be used to determine low dose IL- 2 responsiveness in a subject having an inflammatory bowel disease. The materials and methods can be used to determine low dose IL- 2 responsiveness in a blood sample prior to administering a low dose IL-2 therapy.
G01N 33/554 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 37/00 - Drugs for immunological or allergic disorders
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12Q 1/6816 - Hybridisation assays characterised by the detection means
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Described in certain example embodiments herein are engineered Anti-CRISPR (Acr) polypeptides having an Acr polypeptide and one or more cell -penetrating peptides (CPPs) operatively coupled to the Acr polypeptide. Also described in several example embodiments herein are methods of producing and purifying Acr polypeptides and delivering engineered Acr polypeptides to a cell or cell population.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Provided herein are methods and compositions comprising pharmacological inhibitors of HIF hydroxylases (e.g., or more inhibitors of Prolyl Hydroxylase Domain enzymes (PHDs) or Factor Inhibiting HIF (FIH)) for enhancing cyanide resistance in living organisms.
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
A61P 43/00 - Drugs for specific purposes, not provided for in groups
35.
COMPOSITIONS AND METHODS FOR DONOR-SPECIFIC ANTIBODY SCREENING AND TISSUE TYPING
in vivoin vivo zebrafish models and screening methods disclosed facilitate the study and discovery of therapeutic compounds to treat sodium channel-related cardiac diseases, e.g., by increasing sodium channel function at the membrane.
Described herein are chimeric antigen receptors (CARs) comprising an extracellular domain comprising a portion of an anti-triggering receptor expressed on myeloid cells 2 (TREM2) scFv for targeting macrophages expressing TREM2. Methods for producing and utilizing cells comprising the CAR are further provided herein.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/62 - DNA sequences coding for fusion proteins
A61K 39/00 - Medicinal preparations containing antigens or antibodies
38.
SYSTEM AND METHOD FOR LINKING PATIENT LEVEL MOLECULAR DATA TO TREATMENT SELECTION
Pulmonary arterial hypertension (PAH) exhibits an obliterative vasculopathy where complex, integrated pathobiological signaling pathways drive vascular remodeling. In PAH, the arteriopathy includes numerous endophenotypes that occur to differing extents across patients. Variability in the proteomic and genetic profile is observed, causing phenotypic heterogeneity and inconsistent clinical responses to drug therapies. We have used network medicine to discover modifiable therapeutic targets in PAH by generating patient-specific protein-protein interaction (PPI) networks to unmask molecular interactions that identify and distinguish groups of individual patients with the same clinical phenotype. This allows personalized clinical phenotyping in PAH in those patient groups. The findings here also clarify the relationship between PAH genetic risk and pathobiology on an individual patient level, and inform treatment rationales and personalized drug selection using the PPI networks. Overall, findings from this project will advance precision medicine in PAH with direct relevance to the clinical management of patients.
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
KLRB1 binding agents (in particular anti-KLRB1-antibodies and antigen binding portion thereof) with increased humanness and compositions thereof, as well as therapeutic methods of using the agents, e.g., for activating immune cells, for the treatment of cancer.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The invention features compositions and methods for treating transplant recipients (e.g., chronic allograft rejection) using a senolytic agent and an angiotensin II receptor antagonist or using a senolytic agent and senomorphic agent. The methods and compositions are useful in a variety of transplant settings including, without limitation, solid organ transplants including kidney, lung, heart, liver, intestine, or pancreas transplantation procedures and cellular transplants including but not limited to bone marrow transplants.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
41.
LIPID NANOPARTICLES FOR THE TREATMENT OF VASCULAR DISEASES
Described herein are lipid nanoparticle (LNP) formulations with demonstrated tropism towards smooth muscle cells. Also described herein are LNPs conjugated with peptides that can target tissue or cell surface receptors. The formulations of the disclosure include amounts of DOTAP, an ionizable lipid, amounts of a neutral lipid; amounts of cholesterol; and amounts of one or more PEG-lipids with preferential tropism towards vascular smooth muscle cells (vSMCs). Also described herein are peptides that target receptors highly expressed on the surface of vSMCs (1L-6R, CD63 and GAL-3) or that target proteins in the extracellular matrix adjacent to vSMCs (Col-IV) increasing the uptake into these cells.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 9/1272 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
42.
ENPP1 GENE THERAPY FOR THE TREATMENT OF VASCULAR DISEASE
Provided herein are compositions and methods for gene therapy for disorders of arterial calcification as well as Generalized Arterial Calcification of Infancy (GACI). The methods include a gene addition strategy to deliver a DNA construct to target tissues (such as liver and smooth muscle cells) to express soluble recombinant ENPP1 (srENPP1) or transmembrane full-length recombinant ENPP1 (rENPP1).
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Featured are methods of identifying (e.g., diagnosing) and/or treating a subject having or at risk of developing a liver disorder, such as liver steatosis, liver fibrosis, liver cirrhosis, and/or liver cancer (e.g., HCC). The methods utilize predictive and/or diagnostic biomarkers for identifying a subject as having or having a risk of a liver disorder. The predictive and/or diagnostic biomarkers described herein can also be used to monitor the status of a subject determined to have liver disorder or a risk thereof during treatment with a liver therapy. Also disclosed are methods of treating a subject determined to have a liver disorder (e.g., liver cancer, such as HCC) or a risk thereof (e.g., by assessing the level of one or more of the disclosed biomarkers by administering a liver therapy to the subject.
The present disclosure describes a method of preparing a bioadhesive, pectin- based polymer film. The method includes mixing high-methoxyl pectin (HMP) and water to form an HMP putty ball; hydrating a surface of the HMP putty ball; pressing the HMP putty ball into an HMP film of a substantially uniform thickness; re- hydrating the HMP film; and de-watering the re-hydrated HMP film to a point of at least partial gel-to-glass phase transition. Methods of treating a wound of a subject in need thereof using the bioadhesive, pectin-based polymer film are also described.
Disclosed are compositions, kits, systems, and methods for treating or healing a wound. The compositions can include a carrier composition with a gas-entrapping material and a gas entrapped within the carrier composition.
A61K 33/00 - Medicinal preparations containing inorganic active ingredients
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
This disclosure provides novel integrases for site-specific genetic engineering. Also provided are systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE) with the novel integrases.
Featured are methods of treating an inflammatory condition or disorder in a subject in need thereof. The methods involve administering to the subject a therapeutically effective amount of an agent that reduces expression of or inhibits an activity of Granzyme K (GZMK).
A61K 38/57 - Protease inhibitors from animalsProtease inhibitors from humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
Described herein are methods and compositions that can be used to treat subjects with cancer by administering combinations of antibodies that target TIGIT and antibodies that target Jag1.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
THE BRIGHAM AND WOMEN'S HOSPITAL INCORPORATED (USA)
Inventor
Athanasiou, Lampros
King, Franklin
Hata, Nobuhiko
Kobayashi, Satoshi
Masaki, Fumitaro
Wollin, Daniel Arthur
Abstract
Disclosed are a device and a method of autonomous stone ablation during laser lithotripsy, the method including inserting a catheter into a lumen; navigating the catheter through the lumen along an insertion trajectory; obtaining at least one image of an object within the lumen; segmenting the at least one image; determining a size of the object; and in response to the size exceeding or being equal to a predetermined size: defining a region of lasing of the object, aligning a tip of the catheter with the region of lasing, and performing lithotripsy.
A61B 18/24 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibreHand-pieces therefor with a catheter
A61B 18/26 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibreHand-pieces therefor for producing a shock wave, e.g. laser lithotripsy
A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
G16H 40/60 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
A61B 18/00 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
THE BRIGHAM AND WOMEN'S HOSPITAL INCORPORATED (USA)
Inventor
Masaki, Fumitaro
Kato, Takahisa
Ninni, Brian
Hata, Nobuhiko
King, Franklin
Abstract
Examples of autonomous navigation, movement detection, and/or control include, but are not limited to, autonomous navigation of one or more portions of a continuum robot towards a particular target, movement detection of the continuum robot, Follow-The-Leader smoothing, and/or state change(s) for a continuum robot. Examples of applications include imaging, evaluating, and diagnosing biological objects, such as, but not limited to, for Gastro-intestinal, cardio, bronchial, and/or ophthalmic applications, and being obtained via one or more optical instruments, such as, but not limited to, optical probes, catheters, endoscopes, and bronchoscopes. Techniques provided herein also improve processing and imaging efficiency while achieving images that are more precise, and also achieve devices, systems, methods, and storage mediums that reduce mental and physical burden and improve ease of use.
G16H 40/60 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
51.
COMBINATION THERAPY WITH VENETOCLAX AND ZOTATIFIN FOR THE TREATMENT OF CANCER
The invention features methods of treating a subject having a cancer (e.g., leukemia (e.g., acute myeloid leukemia), solid tumor, breast cancer, lung cancer, colorectal cancer, or pancreatic cancer) by administering venetoclax or a pharmaceutically acceptable salt thereof in combination with zotatifin or a pharmaceutically acceptable salt thereof.
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 35/02 - Antineoplastic agents specific for leukemia
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
52.
IMIDAZO-PYRAZINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF NEUROLOGIC DISORDERS
The present disclosure relates to compounds of Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: Ring A is or, and to their pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting EphB3 and may be used in the treatment of disorders in which EphB3 activity is implicated, such as neurodegenerative diseases and cancers.
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The present disclosure relates to compounds of Formula (I): (I), and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting EphB3 and may be used in the treatment of disorders in which EphB3 activity is implicated, such as neurodegenerative diseases and cancers.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 29/02 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
54.
COMPOSITIONS AND METHODS FOR REGULATING CARDIAC ANGIOGENESIS POST ISCHEMIA
Described herein are compositions (e.g., an inhibitory nucleic acid molecule) for reducing expression of decorin (DCN) and methods thereof for (i) treating a medical condition resulting from a myocardial infarction (Ml), and/or (ii) promoting angiogenesis in a subject. The inhibitory nucleic acid molecule may be a small interfering RNA (siRNA), a double-stranded RNA (dsRNA), an anti-sense oligonucleotide (ASO), a microRNA (miRNA), or a short hairpin RNA (shRNA)), or a gapmeR described herein, or a composition (e.g., pharmaceutical composition) thereof. Advantageously, the composition described herein provides therapeutic effects (e.g., angiogenesis) for cardiac tissue following myocardial infarction (Ml).
Described herein are compositions (e.g., an inhibitory nucleic acid molecule) for reducing expression of small EDRK-rich factor 2 (SERF2) and methods thereof for (i) treating cardiovascular disease (e.g., PAD, CAD, heart failure, cardiomyopathy, or stroke) in a subject; (ii) treating or reducing the likelihood of CTLI in a subject; (iii) alleviating chronic ischemic rest pain in a subject having CTLI; and/or (iv) promoting angiogenesis in a subject (e.g., a subject having or at risk of developing a cardiovascular disease). The inhibitory nucleic acid molecule may be a small interfering RNA (siRNA), a double-stranded RNA (dsRNA), an anti-sense oligonucleotide (ASO), a microRNA (miRNA), a short hairpin RNA (shRNA), or a gapmeR described herein, or a composition (e.g., pharmaceutical composition) thereof.
Disclosed herein are inhibitory nucleic acid molecules (e.g., a small interfering RNA (siRNA), a double-stranded RNA (dsRNA), an anti-sense oligonucleotide (ASO), a microRNA (miRNA), or a short hairpin RNA (shRNA)), or a gapmeR) for reducing expression of the long noncoding RNA (IncRNA) epigenetically induced MYC interacting IncRNA1 (EPIC1). Also disclosed herein are methods for treating arteriosclerosis (e.g., atherosclerosis, e.g., diabetes-associated atherosclerosis) in a subject using the EPIC1 inhibitory nucleic acid molecules.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE (Australia)
Inventor
Yeo, Boon Thye Thomas
Kong, Ru
Asplund, Christopher Lee
Xue, Aihuiping
Tor, Phern Chern
Tan, Xiaowei
Siddiqi, Shan H.
Fox, Michael D.
Cocchi, Luca
Burgher, Bjorn
Abstract
Disclosed is a method for determining a treatment to be applied to a brain of a patient, such as determining a transcranial magnetic stimulation (TMS) treatment location(s) and treatment strength to be applied to a brain of a patient suffering from depression. A search of the brain, based on coarse-scale parcellations, treatment metric and one or more anatomical metrics, is conducted to select the treatment location(s). In one embodiment, this involves progressively varying a value of a parameter associated with a gyrus threshold and for each value, identifying candidate treatment locations based on a functional connectivity of a subgenual anterior cingulate cortex during resting-state functional magnetic resonance imaging (fMRI) recorded over a plurality of multimodal brain imaging sessions, and selecting as the respective treatment location the candidate location that is closest to all other candidate treatment locations.
G16H 20/00 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
A61N 2/04 - Magnetotherapy using magnetic fields produced by coils, including single turn loops or electromagnets using variable fields, e.g. low frequency or pulsating fields
ASSOCIATION FRANCAISE CONTRE LES MYOPATHIES (France)
Inventor
Djeffal-Vincentelli, Yannis
Pourquie, Olivier
Abstract
A composition of INFRA cells is described. The composition includes human muscle stem cells (SCs) expressing the transcription factor PAX7 and lacking the expression of the transmembrane receptor PDGFRA, wherein at least 70% of the population of human muscle SCs are PAX7+ and PDGFRA-. Methods of preparing the INFRA cell compositions, and methods of using the INFRA cells to treat muscle injury are also described.
ASSOCIATION FRANCAISE CONTRE LES MYOPATHIES (France)
Inventor
Djeffal-Vincentelli, Yannis
Pourquie, Olivier
Rodriguez De La Rosa, Alejandra
Abstract
Systems and methods are provided for generating a cell differentation protocol for a target cell type. A low-dimensional graph is generated from a genomics dataset representing a target cell type. The low-dimensional graph is analyzed to determine a set of trajectories within the low-dimensional graph. A score is assigned to each of the set of trajectories based on gene expression associated with the target gene within the trajectory. A trajectory of the set of trajectories having a best score is selected.
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 99/00 - Subject matter not provided for in other groups of this subclass
The present invention relates to a method of treating inflammation in a mammal in need thereof that involves providing a mammal with elevated host endogenous reverse transcriptase produced by host endogenous retroviruses (ERVs), and thereafter contacting in vivo the reverse transcriptase with a reverse transcriptase inhibitor in an amount sufficient to ameliorate ERV- induced inflammatory response.
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
62.
METHODS OF TREATING CARDIOVASCULAR DISEASE ASSOCIATED WITH CALCIFICATION
The invention features methods of treating cardiovascular disease associated with calcification (e.g., aortic stenosis, coronary atherosclerosis, PAD, vein graft failure, AV fistula failure, bicuspid aortic valves, myocardial calcification, pericardial calcification, portal vein calcification, calcific uremic arteriopathy, and Hutchinson-Gilford progeria syndrome) by administering to the subject pemafibrate or a pharmaceutically acceptable salt thereof.
COMBINATIONS OF FORALUMAB WITH GLUCAGON-LIKE PEPTIDE 1 (GLP-1) AGONISTS OR SODIUM-GLUCOSE COTRANSPORTER-2 (SGLT2) INHIBITORS AND METHODS OF USE THEREOF
This disclosure relates to composition and methods for the treatment, prevention and reduction of a comorbidity associated with chronic inflammation such as obesity, Type 1 Diabetes (T1), Type 2 Diabetes (T2D), metabolic syndrome, chronic kidney disease, and cardiovascular risk, as well as methods for improving the efficacy of GLP-1 agonists.
in vivo in situ in situ in a subject. In particular, the solid oral dosage forms, methods, and kits disclosed herein are particularly useful for drugs that require more than once daily administration (e.g, drugs that have short half-lives).
A61K 9/24 - Layered or laminated unitary dosage forms
A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
A61K 31/43 - Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
1112122 are linking molecules. Molecules according to the present invention find use, for example, in multifunctional chimeric molecules (e.g., bifunctional molecules), which make substrate modifications such as post-translational modifications to targets that are not the natural substrate; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.
Systems and methods are provided for providing natural language decision support for pathology. A lower-dimensionality representation of each of a set of received pathology image is generated and a first set of tokens is generated from the representations of the set of pathology images by projecting the lower-dimensionality representations of the received pathology images to a same dimension as an embedding space of a large language model for text tokens or through multimodal blocks added to the large language model such as cross-attention. The large language model is trained on an instruction dataset complied from a plurality of pathology-related sources. A second set of tokens associated with a natural language prompt is received at the large language model. A response is determined from the first set of tokens and the second set of tokens at the large language model.
G06F 16/40 - Information retrievalDatabase structures thereforFile system structures therefor of multimedia data, e.g. slideshows comprising image and additional audio data
G06F 16/483 - Retrieval characterised by using metadata, e.g. metadata not derived from the content or metadata generated manually using metadata automatically derived from the content
G06F 16/487 - Retrieval characterised by using metadata, e.g. metadata not derived from the content or metadata generated manually using geographical or spatial information, e.g. location
G06F 16/50 - Information retrievalDatabase structures thereforFile system structures therefor of still image data
G06F 16/532 - Query formulation, e.g. graphical querying
This disclosure relates to GABA-A receptor positive allosteric modulators such as compounds of Formula (I), and pharmaceutically acceptable salts thereof, which are useful in treating neurological disorders, such as essential tremor, epilepsy, and seizure.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
68.
INFORMATION PROCESSING APPARATUS AND INFORMATION PROCESSING METHOD
An information processing apparatus according to an embodiment includes processing circuitry. The processing circuitry is configured to generate at least a part of a first inference model that, upon receipt of an input of at least one two-dimensional image included in a three-dimensional image, outputs a first inference result corresponding to the two-dimensional image and a second inference model that, upon receipt of an input of two or more of the first inference results, outputs a second inference result corresponding to the three-dimensional image.
G06N 3/043 - Architecture, e.g. interconnection topology based on fuzzy logic, fuzzy membership or fuzzy inference, e.g. adaptive neuro-fuzzy inference systems [ANFIS]
G06N 7/00 - Computing arrangements based on specific mathematical models
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
Provided herein are methods and kits for the rapid testing of biomarkers in human skin that are upregulated within 24 hours, across a range of dosages, to identify patients who have been exposed to radiation.
G01N 33/567 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent utilising isolate of tissue or organ as binding agent
G01N 33/483 - Physical analysis of biological material
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY (Republic of Korea)
Inventor
Lee, Yuhan
Karp, Jeffrey M.
Park, Seongiun
Nam, Kum Seok
Park, Geonhu
Kim, Yeji
Hwang, Kiwook
Abstract
A pressure-sensitive adhesive (PSA), method of manufacturing a PSA, and various uses thereof synergistically combines the advantages of viscoelastic PSAs and bioadhesives. Enabled by a one-pot scalable copolymerization of a polyester and hydrophilic polymer, the PSA provides near-instant (~ 1 s), robust, and repeatable (over 1,000 times) adhesion to wet biological tissues (i.e., skin, lung, heart) and engineering (i.e., metals, plastics) substrates without prior surface functionalization.
A61F 13/0246 - Adhesive bandages or dressings characterised by the skin-adhering layer
C09J 167/03 - Polyesters derived from dicarboxylic acids and dihydroxy compounds the dicarboxylic acids and dihydroxy compounds having the hydroxy and the carboxyl groups directly linked to aromatic rings
C09J 7/25 - PlasticsMetallised plastics based on macromolecular compounds obtained otherwise than by reactions involving only carbon-to-carbon unsaturated bonds
73.
COMPOSITIONS AND METHODS FOR CHARACTERIZING HEPATOCYTE STRESS
The disclosure provides compositions and methods for identifying subjects having hepatocyte stress associated with a risk for developing hepatocellular carcinoma (HCC), and therapeutic methods for reducing a subject's risk of HCC, for example, by inhibiting RELB, SOX4, or HMGCS2.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
74.
SYSTEMS AND METHODS FOR EVALUATION OF CIRCADIAN RHYTHM AND SLEEP HOMEOSTASIS
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. (USA)
Inventor
Mignot, Emmanuel
Specht, Adrien
Duffy, Jeanne F.
Abstract
Systems and methods for assessment of circadian rhythm and sleep homeostasis are described. Presence of proteinaceous biomarkers within an individual's biological sample can be utilized in a computational classifier to indicate rhythmic phase and/or sleep homeostasis. Further clinical analysis and/or treatments can be performed based on determined rhythmic phase or sleep homeostasis.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
A61B 5/1455 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value using optical sensors, e.g. spectral photometrical oximeters
A61B 5/02 - Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
75.
TREATMENT OF SOLID TUMORS WITH IMPLANTABLE POLYMERS WITH SMALL MOLECULES OR CELLS
Disclosed are implantable polymers that release therapeutic agents in proximity to a tumor in a patient. In some embodiments, a polyethylene glycol hydrogel can release a STING agonist and/or a CAR-T cell in proximity to a phosphatase and tensin homolog (PTEN)-null triple negative breast cancer (TNBC) in the patient.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 9/52 - Sustained or differential release type
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
Disclosed are implantable polymers that release therapeutic agents in proximity to a tumor in a patient. In some embodiments, a polyethylene glycol hydrogel can release a small molecule, like a STING agonist in proximity to a phosphatase and tensin homolog (PTEN)-null triple negative breast cancer (TNBC) in the patient.
Methods of predicting relapse in a patient post HSCT, and methods of treatment, the methods including obtaining a bone marrow sample from the patient post- transplantation; and determining TCR clonal diversity of a population of T cells within the bone marrow sample; wherein TCR clonal diversity is indicative of risk of relapse.
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Described herein are termination-readthrough-based gene switches that are small (only 9 nucleotides) and do not introduce any foreign protein into the target cell, and that can be used to alter expression levels of transgenes in a cell.
A therapeutic or diagnostic delivery system, and methods of making and using the same, are disclosed. The system is a solvent free, injectable, biodegradable, and in situ crosslinking depot (ISCD) platform for ultra-long-term release of hydrophilic drugs.
A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 9/00 - Medicinal preparations characterised by special physical form
The present disclosure related to methods of treating various diseases that can benefit from modulating angiogenesis and/or endothelial-to-mesenchymal transition (EndMT) pathways, such as retinopathies and cancer, by modulating family with sequence similarity 222 member A (FAM222A) expression in the endothelium (e.g., endothelial cells) of a subject. For example, FAM222A can be modulated with FAM222A inhibitors described herein, thereby reducing angiogenesis, or FAM222A activators described herein, thereby increasing angiogenesis.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
System, methods, and non-transitory computer readable medium (CRM) are provided that are directed to a biological age model utilizing metabolomic and proteomic data. Additional clinical variables and DNA methylation data may also be delivered to the methods, systems, and CRM. The biological age model determines a morbidity parameter based on a comparison between a patient's determined biological age and their chronological age to determine a time until death and possible treatment strategies.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 15/00 - ICT specially adapted for medical reports, e.g. generation or transmission thereof
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G01N 33/483 - Physical analysis of biological material
A sono-ink composition is described that includes a acrylate oligomer, an acoustic absorber, and a thermal initiator. A method of using the sono-ink for deep-penetrating volumetric printing is also described. The method includes the steps of a) providing a volume of a sono-ink composition, comprising a acrylate oligomer, an acoustic absorber, and a thermal initiator; b) directing a focused acoustic projection of ultrasound waves into the volume of the sono-ink, wherein the focused acoustic projection of ultrasound waves has an intensity and frequency sufficient to activate the thermal initiator so that local polymerization is achieved at a desired region within the volume of sono-ink; and c) optionally repeating step b wherein the focused acoustic projection of ultrasound waves is directed to selected regions within the sono-ink, until a three-dimensional object is formed.
B29C 35/02 - Heating or curing, e.g. crosslinking or vulcanising
A61L 27/54 - Biologically active materials, e.g. therapeutic substances
B29C 64/165 - Processes of additive manufacturing using a combination of solid and fluid materials, e.g. a powder selectively bound by a liquid binder, catalyst, inhibitor or energy absorber
B33Y 70/10 - Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
B33Y 80/00 - Products made by additive manufacturing
C08F 2/56 - Polymerisation initiated by wave energy or particle radiation by ultrasonic vibrations
C08F 265/06 - Polymerisation of acrylate or methacrylate esters on to polymers thereof
C08H 1/00 - Macromolecular products derived from proteins
B29C 64/135 - Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask the energy source being concentrated, e.g. scanning lasers or focused light sources
84.
SYSTEMS AND METHODS FOR TREATING STRESS URINARY INCONTINENCE
The disclosure provides improved methods and devices to create a hammock effect to stabilize the urethra without creating an incision in the abdomen or the vagina, and without using a surgical mesh. Such implementations can also leave no permanent material in the body. The simplicity afforded by such procedures and methods permits treatment of patients on an outpatient basis, and avoids risks and disadvantages associated with the installation of a permanent mesh.
A61B 17/42 - Gynaecological or obstetrical instruments or methods
A61B 17/04 - Surgical instruments, devices or methods for closing wounds or holding wounds closedAccessories for use therewith for suturing woundsHolders or packages for needles or suture materials
Genome wide association studies (GWAS) have demonstrated the power of genetics to detect previously unrecognized contributions to disease biology. To date one limitation has been the modest effect sizes of many of the detected loci, and the lack of a predictable relationship between the locus and specific mechanisms. These features have prevented the large-scale identification of new genetic targets for therapeutic intervention for all but a small number of GWAS loci. To directly address these limitations and build on the success of GWAS, the present disclosure presents a series of specific biological tools and analytics, which when combined with relevant clinical data at scale, enable the systematic discovery of previously unknown disease subsets, previously unknown disease genes of significant effect, previously unknown therapeutic targets, and disease-to-pharmacology matching at the individual patient level.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
86.
INGESTIBLE AND/OR IMPLANTABLE ARTICLES FOR MONITORING ELECTRICAL SIGNALS AND RELATED METHODS
Some aspects of the present disclosure are related to articles for measuring electrical signals internal to a subject, e.g., of the gastrointestinal tract (GI tract). The articles, in some embodiments, are ingestible and/or implantable. In some embodiments, the articles comprise a substrate comprising a plurality of electrodes, the substrate having a Young's elastic modulus of greater than or equal to 0.01 MPa and less than or equal to 200 MPa. In some such cases, the Young's elastic modulus of the substrate facilitates elastic recoil of the substrate such that at least a portion of the plurality of electrodes contact a surface of a tissue at the location internal to the subject (e.g., the GI tract) and thus facilitate measurement of electrical signals at the location internal to the subject. Other aspects are related to methods of using the articles, for example, to monitor electrical signals from the location internal to the subject.
C07K 5/03 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link in which at least a delta-amino acid is involved, e.g. isosteres
in situin situin situ after injection into the tissue of the subject, wherein molecules of the drug are released via surface erosion from the implant. The implant may include a packing efficiency above 97%, and the drug may comprise microcrystals. The composition may be injectable by hand using a needle with a gauge of in a range of 16-30G, wherein the injection by hand includes less than 64 N of force at a 6 mL/minute injection rate.
An intra-abdominal injection system includes a fluid reservoir, a needle, a plunger, and a dissolvable capsule. The plunger is movable between a first position and a second position. When the plunger moves between the first and second position, a fluid from the fluid reservoir flows through the needle. The dissolvable capsule encases each of the fluid reservoir, the plunger, and the needle such that, until the capsule is dissolved during ingestion of the intra-abdominal injection system, the plunger is restricted from being moved from the first position to the second position.
Methods for risk assessment, diagnosis, monitoring during therapy, or monitoring for recurrence for patients with known or suspected ovarian cancer are provided. These methods employ a statistical model and combine detection of microRNA biomarkers and protein biomarkers.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
Aspects of the present disclosure relate to an article. In some embodiments, the article is a gastric retention device or a gastrointestinal device. In some embodiments, the article comprises one or more reservoirs comprising a therapeutic payload. In some embodiments, the article comprises one or more triggerable release mechanisms. In some embodiments, the triggerable release mechanism comprises a metal seal. In some embodiments, release of the therapeutic payload is accomplished via electrochemical dissolution of the metal seal. Other aspects of the disclosure relate to methods for delivering a drug using the drug delivery articles disclosed herein.
Provided herein are nanobody-conjugated nanoparticles and methods of use thereof, e.g., for targeted delivery or accumulation of the nanoparticles in selected tissues.
A01N 25/02 - Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of applicationSubstances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
A01N 27/00 - Biocides, pest repellants or attractants, or plant growth regulators containing hydrocarbons
93.
PROGRAMMABLE LIPID NANOPARTICLE DELIVERY VIA CORONA PROTEIN ENGINEERING
Disclosed are compositions comprising a lipid nanoparticle and a modified biomolecular corona. In some embodiments, the modified biomolecular corona comprises a fused cell-specific binding domain. In some embodiments, the modified biomolecular corona protein has been additionally modified such that it does not bind substantially to its natural receptor. In some embodiments, the fused cell-specific binding domain binds to a target cell.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
94.
BIOSENSOR PLATFORM FOR THE RAPID DETECTION OF ANALYTES
Described herein are fusion proteins for detecting analytes in test samples. Also described herein are methods for detecting analytes in test samples using such fusion protein. Further provided herein are systems or kits comprising such fusion proteins for detection of analytes in test samples.
C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving luciferase
Pseudomonas aeruginosaP. aeruginosa)P. aeruginosa), which poses significant health threats to humans. From this, Applicants isolated a compound that effectively activated complement immunity to inhibit bacterial growth. Furthermore, Applicants developed a robust testing platform for complement-recruiting compounds, allowing the streamlined assessment of ternary complex formatoon and the efficacy of novel bifunctional molecules for recruiting the complement system and inhibiting bacterial growth. These findings demonstrate the potential of this approach in combating antibiotic-resistant P. aeruginosa infections, with implications for other bacterial pathogens or diseases.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A method for tracking the location of a tissue mass comprising disposing a J-bar and electrical lead assembly within a needle cannula lumen; disposing the needle cannula within an outer cannula lumen; inserting the outer cannula into the anatomy of the patient; moving the needle cannula distally relative to the outer cannula; applying a force so that the J-bar and electrical lead assembly moves distally such that the fiducial sensor is anchored proximate to the tissue mass; moving the outer cannula and needle cannula proximally in concert, until the distal end of the outer cannula and the distal end of the needle cannula are disposed at the surface of the skin; applying a force so that the expandable basket moves distally, such that the expandable basket is disposed at the surface of the patient's skin with the electrical lead extending between the fiducial sensor and the expandable basket.
The technology described herein relates to methods of inhibiting Peptidoglycan Recognition Protein 1 (Pglyrp1) in order to improve immune-checkpoint inhibitor treatments for cancer and autoimmune diseases.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Insulin therapy revolutionized the care of patients with diabetes, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment for hypoglycemia; however, current dosage forms remain under- utilized due to poor patient compliance. High-density, readily soluble, and thermostable solid glucagon formulations applied with painless, application-specific microneedle-patches can treat hypoglycemia in type 1 diabetes patients who are awake or asleep. On-demand patches can prevent or treat mild hypoglycemia during the day, and enzyme-driven hypoglycemia-responsive patches can release glucagon autonomously during the night. These patches have excellent in vitro glucagon stability, loading, and release kinetics and can treat hypoglycemia in diabetic humans and animals. These delivery systems enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.
Ingestible and/or implantable low power battery and signaling systems are generally provided. Advantageously, the systems and methods described herein may provide, in some embodiments, secure communication such that only authorized users and/or medical professionals can read sensor data and/or send valid commands to a system. Advantageously, the system and methods described herein may provide, in some embodiments, an energy-efficient security protocol to further improve the wireless communication (e.g., of an ingestible and/or implantable article). In some embodiments, the security protocol advantageously provides data encryption to protect sensor and command information and mutual authentication to prevent unauthorized access to both ingestible and external devices.
The present disclosure relates, at least in part, to methods and cells useful for promoting ubiquitination-independent protein degradation and for promoting protein stability using an engineered midnolin protein.
patents
