Abstract: The present disclosure concerns combination therapy for cancer thatutilizes (i) an oncolytic virus; (ii) a virus comprising nucleic acid encoding an immunomodulatory factor; and (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen. In particular embodiments, the virus comprises nucleic acid encoding an immunomodulatory factor comprises nucleic acid encoding IL-12 and/or antagonist anti-PD-L1 antibody.

Abstract: Embodiments of the disclosure include certain formulations for methods of treating urea cycle disorders. The methods encompass compositions that comprise benzoate and phenylbutyrate that may be at certain doses and have certain ratios of the components. The benzoate and phenylbutyrate may act synergistically in treatment of the urea cycle disorders, in particular embodiments.

Abstract: A Magnetic Resonance Imaging (MRI) enhancement agent includes a plurality of particles, each particle including: a metal core; a dielectric shell disposed on the metal core comprising at least one MRI contrast agent; and a metal shell disposed on the exterior surface of the dielectric shell that encapsulates the dielectric shell.

Abstract: A method for predicting a hypoglycemic event or a hyperglycemic event includes (a) collecting one or more data streams, wherein at least one of the one or more data streams includes a glucose (GL) data stream corresponding to a user, (b) determining one or more features based on the one or more collected data streams, wherein at least one of the one or more features is distinct from each of the one or more data streams, (c) generating a prediction of whether or not a hypoglycemic event or a hyperglycemic event will occur by a prediction model based on the one or more features determined at (b), and (d) issuing an alert to the user in response to the prediction generated at (c) including a prediction that a hypoglycemic event or a hyperglycemic event will occur.

Abstract: The present disclosure concerns methods and compositions related to cancer treatment comprising targeting of SRC-3 in immune cells, including T cells such as T regulatory cells. The targeting of SRC-3 in T regulatory cells in particular is effective to eradicate tumors in mammals. In specific cases, the T regulatory cells are subjected to CRISPR ex vivo to produce cells suitable for adoptive cell transfer. In some cases, one or more agents that target SRC-3 are also administered to the individual and/or are exposed to the cells prior to administration.

Abstract: The present disclosure provides methods and compositions related to Natural Killer T cells that are engineered to knock down the expression of one or more endogenous major histocompatibility complex (MHC) gene. The present disclosure also provides engineered CAR NKT cells that resist rejection by allogeneic immune cells both in vitro and in vivo.

Abstract: The present disclosure encompasses methods for generating cells or tissue from existing cells with one or more mutated variants of Yap. In specific embodiments, the disclosure regards treatment of existing cardiomyocytes with one or more mutated variants of Yap that causes them to divide and generate new cardiomyocytes. In specific cases, the mutated variant of Yap has serine-to-alanine substitutions at 1, 2, 3, 4, 5, 6, or more serines of Yap.

Abstract: A method of improving electrical conduction across an impaired region of a tissue (e.g., myocardial tissue), includes applying an electrically conductive wiring carbon nanotube fibers) across the impaired region. The electrically conductive wiring can become associated with non-impaired regions of the tissue on opposite sides of the impaired region by suturing. The method can also be utilized to treat or prevent cardiac arrhythmia in a subject (e.g., ventricular arrhythmia). The electrically conductive wiring includes carbon nanotubes, such as carbon nanotube fibers, Such electrically conductive wiring can be used to transmit electrical signals to a tissue or sense electrical signals from the tissue. Suture threads including carbon nanotubes, such as carbon nanotube fibers, are provided.

Abstract: One aspect of the invention provides a method of generating bacteriophages adapted to infect a target bacterial strain. The method comprises: providing host bacteria that are susceptible to phage as input to a host chemostat containing phage; providing target bacteria that are related to the host bacteria, but not susceptible to phage as input to a target chemostat containing phage; filtering outflows from the host chemostat and the target chemostat to isolate phage from the populations of the host bacteria, the target bacteria, and macromolecules; combining the outflows; and introducing the combined outflow into each of the host chemostat and the target chemostat.

Abstract: Some embodiments are directed to a transcatheter and serially-expandable artificial heart valve, e.g., to be minimally-invasively implanted into a pediatric patient during a first procedure, and then expanded during a second procedure to accommodate for the pediatric patient's growth. Some embodiments include an expandable frame having a compressed, delivery configuration, and an expanded, deployed configuration, in which the valve is implantable within the patient. The valve can have a first working condition when the frame is expanded to a first diameter and a second working condition when the frame is expanded to a second diameter greater than the first diameter. The valve can include a plurality of leaflets configured to accommodate the expansion of the frame and growth of the patient.

Abstract: Embodiments of the disclosure include methods and compositions for the renewal of cardiomyocytes by targeting the Hippo pathway. In particular embodiments, an individual with a need for cardiomyocyte renewal is provided an effective amount of a shRNA molecule that targets the Sav1 gene. Particular shRNA sequences are disclosed.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: Compositions and methods relating to regulation of gene expression are described. In some embodiments, the present disclosure provides compositions and methods for the regulation of gene expression using nucleic acid constructs. In some embodiments, the present disclosure recognizes the utility of alternative splicing in regulation of gene expression in a nucleic acid construct. In some embodiments, the present disclosure recognizes the utility of regulating gene expression utilizing ligand-binding aptamers.

Abstract: The present disclosure relates to machine-learning generalization, and in particular to techniques for regularizing machine-learning The present disclosure relates to machine-learning generalization, and in particular to techniques for regularizing machine-learning models using biological systems (e.g. brain data) to engineer machine-learning-algorithms that can generalize better. Particularly, aspects are directed to a computer implemented method that includes measuring a plurality of biological responses (e.g. neural responses to stimuli or other variables such body movements); generating data (e.g. responses to stimuli) using the predictive model which can denoise biological data and extract task relevant information; scaling and transforming these predictions (e.g. measure representational similarities between stimuli); and using the biologically derived data to regularize machine-learning-algorithms.

Abstract: The present disclosure relates to methods for screening test samples or substances that are capable of inducing or reducing nucleolar hypertrophy in cancer cells. The present disclosure further provides methods of contacting isolated cancer cells with a test sample or a substance that can induce nucleolar hypertrophy in a cancer cell. The present disclosure further provides methods for contacting an isolated cancer cell characterized by nucleolar hypertrophy with a test sample or substance that can reduce the nucleolar hypertrophy. One benefit to the method of screening disclosed herein can be the identification of test samples or substances capable of reducing nucleolar hypertrophy. Another benefit to the method of screening disclosed herein can be the identification of those combinations of test samples, substances, or combinations or series thereof, which are suitable or optimal for treating specific cancers in patients.

Abstract: Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

Abstract: Embodiments of the disclosure include methods of identifying and selecting suitable donors for use in constructing donor minibanks of antigen-specific T cell lines; donor minibanks of antigen-specific T cell lines; and donor banks made up of a plurality of such minibanks. The present disclosure includes methods of treating a disease or condition comprising administering at least one antigen-specific T cell line from such a donor minibank or donor bank to patient (e.g., who has received transplanted material from a transplant donor in a transplant procedure), and methods for selecting the best HLA-matched antigen-specific T cell line in the donor minibank for a particular patient.

Abstract: Methods of treating a cancer, comprising administering to a subject: (i) a virus comprising nucleic acid encoding an antigen-binding molecule comprising: (a) an antigen-binding moiety specific for an immune cell surface molecule, and (b) an antigen-binding moiety specific for a cancer cell antigen; and (ii) an oncolytic virus, and/or (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen are disclosed. Also disclosed are articles and compositions for use in such methods.

Abstract: Embodiments of the disclosure concern systems, methods, and/or compositions for cultivation of mammalian viruses, including at least human noroviruses and sapoviruses within the Caliciviridae family of viruses. The ex vivo culture systems include intestinal enteroids in combination with bile or a functionally active fraction or component thereof. In specific embodiments, the culture system is utilized to test inactivation compounds for therapeutic or environmental efficacy and to test contaminated comestibles and/or environmental entities for determination of the presence of infectious virus. Furthermore, antiviral compositions may be tested using systems of the disclosure, including drugs, small molecule inhibitors, and biologics such as neutralizing monoclonal antibodies.

Abstract: Embodiments of the invention include methods of preventing and/or reducing the risk or severity of an allergic reaction in an individual. In some embodiments, particular small molecules are employed for prevention and/or reduction in the risk or severity of anaphylaxis. In at least particular cases, the small molecules are inhibitors of STAT3. In some cases, the small molecule comprises N-(1?,2-dihydroxy-1,2?-binaphthalen-4?-yl)-4-methoxybenzenesulfonamide.