Abstract: Techniques and systems for monitoring cardiac arrhythmias and delivering electrical stimulation therapy using a subcutaneous implantable cardioverter defibrillator (SICD) and a leadless pacing device (LPD) are described. For example, the SICD may detect a tachyarrhythmia within a first electrical signal from a heart and determine, based on the tachyarrhythmia, to deliver anti-tachyarrhythmia shock therapy to the patient to treat the detected arrhythmia. The LPD may receive communication from the SICD requesting the LPD deliver anti-tachycardia pacing to the heart and determine, based on a second electrical signal from the heart sensed by the LPD, whether to deliver anti-tachycardia pacing (ATP) to the heart. In this manner, the SICD and LPD may communicate to coordinate ATP and/or cardioversion/defibrillation therapy. In another example, the LPD may be configured to deliver post-shock pacing after detecting delivery of anti-tachyarrhythmia shock therapy.

Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

Abstract: Mesothelin (MSLN) is expressed on pancreatic cancers, ovarian cancers and mesotheliomas. The present disclosure provides antigen-binding molecules, including anti-MSLN antibodies, and bispecific antigen-binding molecules that bind to both MSLN and a T cell antigen (e.g., CD3) and activate T cells in the presence of MSLN-expressing tumor cells. The antigen-binding molecules of this disclosure are useful for the treatment of diseases and disorders in which a MSLN-targeted immune response is desired and/or therapeutically beneficial. For example, the antigen-binding molecules of the present disclosure are useful for the treatment of various cancers, including pancreatic cancer, ovarian cancer and mesotheliomas.

Abstract: Single-domain antibodies that bind receptor tyrosine kinase (ROR1) are described. The single-domain antibodies can be used for multiple purposes including in research, imaging, diagnosis, and treatment of ROR1-related conditions. The disclosed single-domain antibodies can be used as anti-cancer therapeutics such as antibody-drug conjugates, multi-domain binding molecules, or recombinant receptors or can be used as cancer imaging/diagnostic agents.

Abstract: Anti-Epstein Barr Virus (EBV) vaccines are described herein. The EBV vaccine antigens are linked to a multimerization domain, for example, presented on a circular tandem repeat protein (cTRP) scaffold or linked to a C4b multimerization domain. The vaccines can be used to treat and/or reduce the risk of EBV infection and to treat and/or reduce the risk of complications associated with EBV infection, such as infectious mononucleosis, lymphoproliferative disorders, carcinomas, and smooth muscle tumors.

Abstract: IgM-multimerized single-domain antibodies that bind receptor tyrosine kinase (ROR1) are described. The IgM-multimerized single-domain antibodies can be used for multiple purposes including in research, imaging, diagnosis, and treatment of ROR1-related conditions and can be conjugated to form multi-domain binding molecules or antibody conjugates.

Abstract: Described herein are peptides and variants and mutants thereof capable of interacting with TEAD, disrupting the HIPPO pathway, or modulating the activity or function of TEAD interactions in a cell. Pharmaceutical compositions and uses of peptides, as well as methods of designing and manufacturing such peptides, to treat cancer, tumor, or any other disease/condition associated with a dysregulated HIPPO pathway or uncontrolled cell growth are also described herein.

Abstract: Described herein are peptides and variants and mutants thereof capable of interacting with TEAD, disrupting the HIPPO pathway, or modulating the activity or function of TEAD interactions in a cell. Pharmaceutical compositions and uses of peptides, as well as methods of designing and manufacturing such peptides, to treat cancer, tumor, or any other disease/condition associated with a dysregulated HIPPO pathway or uncontrolled cell growth are also described herein.

Abstract: Mesothelin (MSLN) is expressed on pancreatic cancers, ovarian cancers and mesotheliomas. The present disclosure provides antigen-binding molecules, including anti-MSLN antibodies, and bispecific antigen-binding molecules that bind to both MSLN and a T cell antigen (e.g., CD3) and activate T cells in the presence of MSLN-expressing tumor cells. The antigen-binding molecules of this disclosure are useful for the treatment of diseases and disorders in which a MSLN-targeted immune response is desired and/or therapeutically beneficial. For example, the antigen-binding molecules of the present disclosure are useful for the treatment of various cancers, including pancreatic cancer, ovarian cancer and mesotheliomas.

Abstract: Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.

Abstract: The present disclosure provides compositions and methods for renal therapy. In various aspects, the present disclosure provides a composition comprising a knotted peptide, wherein upon administration to a subject the knotted peptide homes, targets, is directed to, accumulates in, migrates to, is retained by, and/or binds to renal tissue of the subject. In various aspects, the composition further comprises an active agent coupled to the knotted peptide. The composition, when administered to the subject, may induce protective preconditioning or acquired cytoresistance.

Abstract: Described herein are peptides and variants and mutants thereof capable of interacting with TEAD, disrupting the HIPPO pathway, or modulating the activity or function of TEAD interactions in a cell. Pharmaceutical compositions and uses of peptides, as well as methods of designing and manufacturing such peptides, to treat cancer, tumor, or any other disease/condition associated with a dysregulated HIPPO pathway or uncontrolled cell growth are also described herein.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality, of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.

Abstract: Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: The present disclosure provides compositions and methods for treating cellular hyperproliferative disorders with a PHF5? inhibitor, such as siRNA, shRNA, antisense oligonucleotides, or pharmaceutical compounds. Exemplary cellular hyperproliferative disorders that can be treated with the PHF5? antagonists of the present disclosure include cancers, such as gliomas, adenocarcinomas, cervical cancer or prostate cancer.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: A chlorotoxin conjugate detectable by fluorescence imaging that allows for intra-operative visualization of cancerous tissues, compositions that include the chlorotoxin conjugate, and methods for using the chlorotoxin conjugate.