Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: The invention provides novel non-invasive in vitro methods for assessing the metabolic condition of oocytes and/or embryos with fluorescence lifetime imaging microscope, that can be used, for example, in assessment of oocytes and embryos in assisted reproductive technologies.

Abstract: Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the article includes dimensions configured for transesophageal retrieval. In some cases, the articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Abstract: Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.

Abstract: The systems and methods described herein determine metrics of cardiac or vascular performance, such as cardiac output, and can use the metrics to determine appropriate levels of mechanical circulatory support to be provided to the patient. The systems and methods described determine cardiac performance by determining aortic pressure measurements (or other physiologic measurements) within a single heartbeat or across multiple heartbeats and using such measurements in conjunction with flow estimations or flow measurements made during the single heartbeat or multiple heartbeats to determine the cardiac performance, including determining the cardiac output. By utilizing a mechanical circulatory support system placed within the vasculature, the need to place a separate measurement device within a patient is reduced or eliminated. The system and methods described herein may characterize cardiac performance without altering the operation of the heart pump (e.g., without increasing or decreasing pump speed).

Abstract: The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Abstract: Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.

Abstract: Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

Abstract: Provided are methods of controlling disassociation of cells from a carrier, compositions, and methods of collecting cells. The methods of controlling disassociation of cells from a carrier may include contacting a polymeric carrier with one or more digesting agents to disassociate at least a portion of a plurality of cells from the polymeric carrier. The polymeric carrier may be crosslinked with a crosslinker including at least one of a redox sensitive moiety, a UV light sensitive moiety, a pH sensitive moiety, and a temperature sensitive moiety.

Abstract: New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Abstract: Improvements in ingestible electronics with the capacity to sense physiologic and pathophysiologic states have transformed the standard of care for patients. Yet despite advances in device development, significant risks associated with solid, non-flexible gastrointestinal transiting systems remain. Here, we disclose an ingestible, flexible piezoelectric device that senses mechanical deformation within the gastric cavity. We demonstrate the capabilities of the sensor in both in vitro and ex vivo simulated gastric models, quantified its key behaviors in the GI tract by using computational modeling, and validated its functionality in awake and ambulating swine. Our piezoelectric devices can safely sense mechanical variations and harvest mechanical energy inside the gastrointestinal tract for diagnosing and treating motility disorders and for monitoring ingestion in bariatric applications.

Abstract: The disclosure describes systems and methods for separating a plurality of molecular entities with differing densities. The system includes: a pair of magnetic poles of like polarity to provide a magnetic field; and a container holding the plurality of molecular entities in a fluid medium comprising nanoparticles that substantially change a magnetic susceptibility of the fluid medium such that, when the container is placed inside the magnetic field, sufficient gradients in an effective density of the fluid medium are generated inside the container to levitate the plurality of molecular entities to respective layers within the container, each respective layer corresponding to a respective density.

Abstract: Delivery systems and their methods of use for delivering one or more therapeutic compounds to a user are described. A delivery system may include an implantable pump and an external actuator. The implantable pump may include an actuatable portion that may be actuated to dispense a volume of fluid. The external actuator may include a pusher configured to deform skin to engage an actuatable portion of the pump. The external actuator may also include a positioning magnet configured to magnetically attract a portion of the implantable pump such that the external actuator and the pump may be aligned prior to applying force to the portion of the skin between the external actuator and the actuatable portion of the pump.

Abstract: The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.

Abstract: Systems and techniques for generating and/or employing a medical imaging stroke model are presented. In one example, a system employs a convolutional neural network to generate output data regarding a brain anatomical region based on diffusion-weighted imaging (DWI) data associated with the brain anatomical region and apparent diffusion coefficient (ADC) data associated with the brain anatomical region. The system also detects presence or absence of a medical stroke condition associated with the brain anatomical region based on the output data.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Methods of manufacturing tissue interfacing components, such as solid needles comprising one or more therapeutic agents, are disclosed. In some embodiments, a method for manufacturing a tissue interfacing component comprises compressing a granular therapeutic agent within a mold cavity of a mold to form a solid tissue interfacing component. The mold cavity may define an elongated shape extending along a longitudinal axis from an opening of the mold cavity to a distal end of the mold cavity, and the granular therapeutic agent may be compressed by moving a mold punch along the longitudinal axis towards the distal end. After compressing the granular therapeutic agent to form the solid tissue interfacing component, the tissue interfacing component may be removed from the mold and subsequently inserted into tissue to deliver the therapeutic agent to a subject.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.