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 present invention is based, in part, on the identification of methods of modulating PD-1 expression and/or activity in regulatory T cells (Tregs) to thereby regulate effector immune responses in effector T cells (Teffs).

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

Abstract: Exemplary methods, apparatus, and systems are disclosed for automated registration and motion compensation of patient-mounted needle guide medical devices using fiducial markers, and processing algorithms where a re-registration step is provided. These methods, apparati, and systems adaptively compensate for the displacement of the medical device and/or target location due to the patient movement or internal organ motion.

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 certain embodiments, the self-righting article a tissue-interfacing components. In some embodiments, each tissue-interfacing component may comprise an electrically-conductive portion configured for electrical communication with tissue and an insulative portion configured to not be in electrical communication with tissue.

Abstract: The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, POU2AF1 modulation is provided for use as a marker, marker signature and molecular target. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

Abstract: The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to poly-N-acetyl glucosamine (PNAG), such as Staphylococcal PNAG, in acetylated, partially acetylated and/or fully deacetylated form. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of infections by bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Some antibodies of the invention enhance opsonophagocytic killing and in vivo protection against bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.

Abstract: Articles for rapid release of components including, for example, quick release capsules, are generally provided. Advantageously, in some embodiments, the articles described herein may be configured to prevent fluid from contacting a component h contained therein (e.g., tissue interfacing component) or payload contained therein until a desired time, e.g., the time at which the component is configured to release from the article to a location internal to a subject (e.g., localize to a tissue wall in the subject). In some embodiments, the article comprises a first compartment and a second compartment not in fluid communication with the first compartment. In some embodiments, the first compartment and second compartment are fluidically isolated. For example, in some cases, the first compartment comprises a mechanism for releasing a component contained within the article and the second compartment comprises the component.

Abstract: The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, GATA3 and/or FOXO1 modulation are provided for use as markers, marker signatures and molecular targets. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

Abstract: The invention provides a collection of gene expression signatures that is linked to longevity. Also provided herein are assays, methods, and systems for identifying a treatment that can modulate lifespan or determining an effect of a treatment on a health profile of a subject by using the collection of gene expression signatures described herein.

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: Systems and methods for analyzing metabolite concentration in a subject using a medical imaging system are provided. The method includes, using a nuclear magnetic resonance (NMR] system, acquiring data from a subject during multiple acquisitions using different echo times for the multiple acquisitions to create a chemical shift domain. The method also includes, using the chemical shift domain, identifying metabolites by at least two chemical shifts and generating a report indicating the metabolites.

Abstract: The technology described herein is directed methods of treating an extracellular vesicle (EV)-associated disease or vascular calcification in subject by administration of an agent that reduces the levels or activity of Annexin A1 (ANXA1).

Abstract: Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence 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 residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Abstract: Embodiments of the invention provide a retrieval device and method for retrieving tissue from a body cavity. The retrieval device includes a pouch having an aperture and a pouch wall defining an interior space. An inflatable rim is coupled to the pouch and facilitates retrieval of the tissue into the interior space of the pouch. The retrieval device further includes a closure device coupled to the pouch wall for enclosing the tissue within the interior space of the pouch. A portion of the pouch wall includes a self-sealing characteristic that allows an instrument to pierce the pouch wall and the pouch wall is resealable after withdrawal of the instrument. The pouch can move from a retracted position to a expanded position upon inflation of the inflatable rim, which can then be separated by application of a separation force at an area of material weakness in the pouch wall.

Abstract: Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

Abstract: In one aspect, the invention features a method for identifying a drug-modulated polypeptide substrate of cereblon (CRBN). In another aspect, the invention features a method of identifying a polypeptide target of a modulator of CRBN. In yet another aspect, the invention provides methods of monitoring or characterizing the sensitivity of a subject to a modulator of CRBN.

Abstract: The invention relates to method for identifying and selecting a subject with increased risk of developing a cardiometabolic disease and optionally, providing a personalized medicine method, which may involve sequencing at least part of a genome of one or more cells in a blood sample of the subject and identifying from said sequencing one or more mutations in one or more somatic mutations.

Abstract: A stent apparatus, system, and method that senses wall shear stress by measuring fluid flow at localized areas within the stent, that processes measured information through an integrated circuit, and selectively sends power to mechanically controllable stent surfaces which results in localized geometric changes. In various embodiments the stent apparatus, system, and method sends data to outside the body in real time.

Abstract: This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.