Abstract: A device and system for flushing a shunt catheter utilizes the available cerebrospinal fluid (CSF) to flush a blocked catheter. The CSF is pressurized to a predetermined amount and then allowed to suddenly, rapidly and forcefully purge any occlusions. The rapid release of CSF produces flow jets from the catheter pores into the ventricle. This impulse, or “cough”, will push and divert choroid plexus and/or other blockages away from the pores. The device and system may then be allowed to refill at a slow rate, thus reducing the possibility of rapid suction of fluid back into the system and the attendant possibility of drawing the choroid plexus back into the pores. The catheter at the proximal end may also include back-up pores that can be opened to restart flow from the ventricle should the primary pores remain blocked after a flushing attempt.

Abstract: Provided herein, in some aspects, are delivery vehicles comprising a ceramide and an agent to be delivered attached to the ceramide. In some embodiments, the ceramide does not comprise a fatty acid (i.e., is a sphingosine). In some embodiments, the ceramide comprises a fatty acid. In some embodiments, the ceramide is a glycoceramide. In some embodiments, the agent is attached to the ceramide covalently (e.g., via a linker). In some embodiments, the agent to be delivered is a therapeutic agent. The ceramide is able to deliver the agent to a cell or to a cellular compartment, as well as across the musical barrier. In some embodiments, agents delivered using the ceramide described herein exhibit longer half-life, compared to agents delivered alone. Methods of delivering a therapeutic agent to a subject for treating a disease using the ceramide delivery vehicle are also provided.

Abstract: A replacement heart valve device is disclosed. In some embodiments, the device includes a frame coupled to one or more leaflets that are moveable between open and closed configurations. In some embodiments, the frame comprises at least two frame sections that join at a pair of commissural posts. In some embodiments, the device may be geometrically accommodating to adapt to different vasculature shapes and sizes and/or to be able to change size while implanted within a growing patient.

Abstract: The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.

Abstract: As described below, the present invention features compositions and methods for neuroprotection and/or neuroregeneration of damaged or degenerating neurons. In various embodiments, the compositions and methods of the present disclosure are used to treat a neurodegenerative disease and/or nervous system injury. The methods in various embodiments include reducing or eliminating activity or expression of a target gene(s) and/or a polypeptide(s) expressed by a target gene(s) in a neuron.

Abstract: Described herein are methods and compositions for treating cancer. Aspects of the invention relate to administering to a subject having cancer an asparaginase and an agent that inhibits G6PD. Another aspect of the invention relates to administering an asparaginase to a subject having cancer that comprises a G6PD deficiency.

Abstract: The disclosed invention provides a method of treating a central nervous system (CNS) disease or disorder comprising administering to a subject diagnosed with the CNS disease or disorder a composition comprising a population of genetically modified, programmed cell death-1 receptor ligand (PD-L1)+-expressing hematopoietic stem cells (HSCs), wherein the CNS disease or disorder involves inflammation of the CNS. In one embodiment, the CNS disease or disorder is Multiple Sclerosis (MS). In certain aspects, the hematopoietic stem cells (HSCs) are obtained from a subject having a CNS disease or disorder prior to modification.

Abstract: Surgical simulation devices and their methods of use are described. In some embodiments, a surgical simulation device includes a base, a first surgical model configured to simulate a first cleft lip condition, and a second surgical model configured to simulate a second cleft lip condition. The device includes a model support configured to be releasably engaged with the base. The first surgical model is disposed on a first surface of the model support and the second surgical model is disposed on a second surface of the model support. The base includes an internal volume sized and shaped to receive one of the first surgical model and the second surgical model. The other of the first surgical model and the second surgical model is at least partially exposed when the model support is engaged with the base.

Abstract: Provided are methods and compositions for treating cerebrospinal fluid disorders. In embodiments, the methods comprise administering an agent to a subject altering activity, expression, or level of NKCC1 in a cell.

Abstract: Described herein are engineered ligand that binds a cell surface receptor (e.g., GPCR), with improved affinity, potency, and specificity. By conjugating a sub-optimal ligand for a cell surface receptor (e.g., GPCR) to a targeting molecule that binds an epitope (natural or exogenous epitope) in the extracellular portion of the cell surface receptor (e.g., GPCR), the affinity, potency, and/or specificity of the sub-optimal ligand is enhanced.

Abstract: Described herein are methods and compositions for producing modified, PD-L1 expressing hematopoietic stem cells, and uses thereof. Aspects of the invention relate to modulating the expression of micro RNA that controls the expression of PD-L1 in the hematopoietic stem cell. Methods for modulating the expression of micro RNA include, e.g., introducing to the cell a nucleic acid encoding a given micro RNA, or an agent that inhibits a given micro RNA.

Abstract: The invention features a prospective respiratory motion compensation technique for cardiovascular magnetic resonance imaging of the whole-heart of a free-breathing subject.

Abstract: Provided herein are products and methods for detecting analytes using polymers that bind to such analytes and thereby undergo a conformational change or contribute to a newly formed complex.

Abstract: Methods and systems for cardiovascular structure reconstruction are provided. A method of reconstructing a cardiovascular structure may include imaging the cardiovascular structure, producing a three-dimensional model of the cardiovascular structure based on the imaging, and creating a three-dimensional model of a patch corresponding to the three-dimensional model of the cardiovascular structure, where the patch is configured to reconstruct the cardiovascular structure to a normal geometry. A patch for a cardiovascular structure may include at least one layer of anisotropic material including an outermost perimeter and one or more notches extending inward from the outermost perimeter, where each of the one or more notches creates a discontinuity in the outermost perimeter. In some cases, each of the one or more notches includes a first edge and a second opposing edge, and the patch further includes one or more sutures configured to secure the first edge to the second opposing edge.

Abstract: The invention provides methods for activating a repressed allele within an imprinting control region, thereby treating an imprinting associated disorder.

Abstract: Disclosed herein are methods for generating mature cardiomyocytes and compositions including mature cardiomyocytes. Also disclosed herein are methods for enhancing maturation of quiescent cardiomyocytes and compositions including mature quiescent cardiomyocytes.

Abstract: This disclosure provides new and improved systems and methods for analyzing binding interactions and for identifying and measuring agents that modulate such binding interactions, including weak binding interactions. The methods may be used in high throughput screening assays.

Abstract: Systems and methods of the present disclosure enable improved seizure detection and/or prediction using a seizure monitoring system. The system receives a data stream including wearable sensor data associated with a user, where the data stream includes electrodermal activity data and where the electrodermal activity data includes circadian rhythm-dependent amplitudes. The system receives a time associated with a seizure of the user. The system trains seizure machine learning model to identify a pre-ictal period associated with a time segment based on the circadian rhythm dependent amplitudes and the time associated with the seizure. The system deploys the seizure machine learning model to ingest a new data stream. Based on the new data stream, the seizure machine learning model predicts a seizure likelihood in a prediction period.

Abstract: Provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Further provided herein are agents that bind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1 Methods of using these agents in treating cancer are also provided.

Abstract: Methods for preparing and using collagen extracts and collagen scaffolds are provided. Additionally methods and related kits for the repair of articular tissue using the collagen material are provided.