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: The compositions and methods provided herein are related, in part, to the discovery of cholic acid 7-sulfate as a treatment for diabetes. Provided herein is a method for treating a metabolic disorder (e.g., diabetes, obesity), or an inflammatory disease (e.g., Crohn's disease, inflammatory bowel disease, ulcerative colitis, pancreatitis, hepatitis, appendicitis, gastritis, diverticulitis, celiac disease, food intolerance, enteritis, ulcer, gastroesophageal reflux disease (GERD), psoriatic arthritis, psoriasis, and rheumatoid arthritis) in a subject in need thereof comprising administering to a subject a compound of Formulae (I)-(XVII).

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 present invention is directed stromal cell derived factor-1 peptides that have been mutated to make them resistant to digestion by the proteases dipeptidyl peptidase IV (DPPIV) and matrix metalloproteinase-2 (MMP-2) but which maintain the ability of native SDF-I to attract T cells. The mutants may be attached to membranes formed by self-assembling peptides and then implanted at sites of tissue damage to help promote repair.

Abstract: Systems and methods related to reconfigurable medical devices are described. In some embodiments, a reconfigurable medical device may include a central core and a plurality of arms. The arms may be rotatably coupled to the central core such that the plurality of arms may rotate outwards away from the central core to selectively reconfigure the reconfigurable device between a retracted configuration and an expanded configuration. In an initial state, the arms may be biased outwards away from the central core into the expanded configuration. When the reconfigurable device is exposed to a temperature greater than a threshold temperature, the arms may be biased towards the central core into the retracted configuration. In some embodiments, a reconfigurable medical device may include therapeutic compound-loaded needles coupled to distal portions of the arms.

Abstract: 3D cell cultures and devices for 3D cell culture, and methods of use thereof are provided. In some embodiments, the 3D cell culture comprise pancreatic ? cells and can be generated in multi-well plates, allowing for high throughput assays on the cell culture.

Abstract: Actuating components and related methods are generally disclosed. Certain embodiments comprise an actuating component associated with a plurality of microneedles (e.g., for administering a therapeutic agent to a subject). In some embodiments, the actuating component may be administered to a subject such that the plurality of microneedles are deployed at a location internal to the subject (e.g., in the gastrointestinal tract). The actuating component may be contained within, in some embodiments, a capsule (e.g., for oral administration to a subject). In some embodiments, the actuating component has a pre-deployment configuration in which the plurality of microneedles have a first orientation and a deployed configuration in which the plurality of microneedles have a second orientation, different than the first orientation.

Abstract: Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a 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 herein are methods and kits for determining the presence or absence of certain microRNA biomarkers in a blood sample of a female patient. The microRNA biomarkers are associated with ovarian cancer. Also provided are methods for screening a female subject for the presence or absence of certain microRNA biomarkers, as well as methods for treating a female subject having an ovarian cancer.

Abstract: The invention relates generally to the use of microvesicle RNA signatures for diagnosis, predicting, and/or to monitor treatment efficacy, including patients who are candidates for renal transplant and/or who have received a renal transplant.

Abstract: There is provided a medical support device for holding and positioning a needle. This device is particularly useful for positioning needles in a less invasive puncture treatment. This device comprises two rotational elements and at least one needle guide attached to a rotational element and. The needle guide guides the direction of insertion of a needle-like instrument and includes a guide portion that guides a needle or other needle-like instrument where the puncture point of the needle in a first position is different from the puncture point when the needle guide guides the needle in a second position.

Abstract: The invention relates to (S)-6-((1 R,2E,4E,8E,10S)-11-(4-fluorophenoxy)-1,10-dihydroxyundeca-2,4,8-trien-6-yn-1-yl)-1,4-dioxan-2-one (compound (1)), which is a lactone-containing analog of lipoxin A4 (LXA4). In particular, the invention features pharmaceutical compositions including compound (1) and the use of compound (1) for the treatment of a disorder (e.g., a fibrotic disorder or an inflammatory disorder, such as an autoimmune disorder) in a subject in need thereof.

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 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: 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: 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.