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: 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: 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: 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.

Abstract: Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

Abstract: Described herein are novel compositions comprising bispecific and multispecific polypeptide agents, and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, that co-express the inhibitory receptors PD-1 and TIM-3. These compositions and methods are useful for the treatment of chronic immune conditions, such as persistent infections or cancer.

Abstract: The present disclosure provides devices and methods for insufflating abdomens of subjects under direct visualization. Such devices and methods, in some implementations, include features for cleaning the devices, and certain implementations of the methods permit procedures wherein it is not necessary to use a typical obturator to place a cannula, resulting in safer procedures.

Abstract: Provided herein are pharmaceutical compositions for local administration of metabolic inhibitors, methods of locally administering such compositions, and rapid diagnostic methods for identifying mutant allele during the course of a surgical procedure.

Abstract: Provided herein are methods of treating or reducing the risk of a cardiovascular disease using a lipid lowering agent (e.g., statin and/or PCSK9 inhibitor) and an anti-inflammatory agent (e.g., a pro-inflammatory cytokine inhibitor). Further provided herein are methods of predicting the recurrence rate of a subject who has received or is undergoing therapy for a cardiovascular disease with a lipid lowering agent on the basis of the C-reactive protein (CRP) level in the subject. In some embodiments, the recurrence rate can be reduced using an anti-inflammatory agent.

Abstract: The technology described herein is directed to methods and compositions for the treatment of hypertension, e.g. pulmonary arterial hypertension, relating to inhibition of TGF?1, TGF?3, and/or GDF-15.

Abstract: Systems and methods execution of a magnetic resonance imaging pulse sequence including a first spin-echo echo planar imaging pulse sequence to acquire first data of a volume, a second spin-echo echo planar imaging pulse sequence comprising a first one or more diffusion gradient pulses to acquire first diffusion data of the volume, a third spin-echo echo planar imaging pulse sequence comprising a second one or more diffusion gradient pulses to acquire second diffusion data of the volume, and a fourth spin-echo echo planar imaging pulse sequence comprising a third one or more diffusion gradient pulses to acquire third diffusion data of the volume, generation of perfusion metrics based on the first data, and generation of diffusion metrics based on the first data, the first diffusion data, the second diffusion data, and the third diffusion data.

Abstract: Provided are methods of treating diabetes and/or obesity in a subject in need thereof, and methods of increasing the amount of cholic acid-7-sulfate (CA7S) in a subject. Further provided herein are methods of administering CA7S to a subject. Also provided are compositions and kits comprising cholic acid-7-sulfate, or a salt thereof for use in the treatment of diabetes and/or obesity.