Abstract: The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.

Abstract: The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.

Abstract: The present disclosure provides a miRNA hairpin that, when processed by a virus-infected cell, increases the therapeutic effectiveness of the virus. The present disclosure also provides a virus encoding such a miRNA hairpin. The present disclosure also provides pre-miRNAs that, when processed by a virus-infected cell, increase extracellular vesicle secretion of the encoded miRNA hairpin by the virus-infected cell.

Abstract: The present disclosure provides a method for stimulating asymmetric division of at least some satellite stem cells in a patient suffering from a disease or disorder characterized by satellite cells having an inability, or a reduced ability, to assemble a functional dystrophin-associated glycoprotein complex (DGC) that results in an inability, or reduced ability, to establish cell polarity. The method includes administering to the patient a sufficient amount of an epidermal growth factor receptor (EGFR) pathway activator to stimulate asymmetric division of at least some satellite stem cells.

Abstract: The disclosure relates to modified vaccinia virus vectors derived from the Copenhagen strain of vaccinia virus, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified Copenhagen-derived vaccinia virus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Abstract: Provided herein are methods for enhancing infection, growth, spread, or titer of an oncolytic RNA virus in a cancer or tumor cell; enhancing the oncolytic activity, cytokine-induced cell death activity, and/or cytotoxic activity of an oncolytic RNA virus in a cancer or tumor cell; upregulating cytokine response to, and/or enhancing the immunotherapeutic activity of an oncolytic RNA virus in a cancer or tumor cell; and/or treating a tumor or cancer in a subject in need thereof. Such methods employ a vanadium-containing compound, administered to the cancer or tumor cells before, after, or concurrently with infection of the cancer or tumor cells with the oncolytic RNA virus. Related compositions, uses, and kits therefor are also provided. Methods for producing RNA viruses, RNA virus-based cancer vaccines, and RNA virus-based cancer gene therapy vectors are also provided.

Abstract: The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Abstract: Provided are compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided.

Abstract: Herein are described methods of treating a human subject having acute myeloid leukemia (AML) that is refractory to induction therapy, wherein an MDM2 inhibitor is administered before or concurrently with chemotherapy, which may comprise induction therapy. Refractory AML may be predicted based on decreased expression of MTF2 in cells from a hematological sample obtained from the subject. Also provided are methods of predicting and treating AML responsive to MDM2/HDM2 inhibitors, based on MTF2 expression. One set of additional biomarkers useful in the predictions comprise one or more of H3K27me3, CD84, CD92, MDM2, NPM1, PRICKLE1, SET, ABCB6, POLQ, POLK, POLH, ARTIMIS, MCM6, CD327, CD90 and PARP1. Another set of additional biomarkers useful in the predictions include at least one of H3K27me3, MDM2, NPM1, SET, CD84 and PRICKLE1. Methods of selecting a patient for treatment with an MDM2 inhibitor before or concurrently with chemotherapy are also provided, along with kits and uses.

Abstract: Provided are compounds of Formula (II) that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided.

Abstract: The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Abstract: There is provided a system and method for applying markings to a three-dimensional virtual image or virtual object, the system comprising a physical stylus, a surface, and a virtual or augmented reality display. A virtual space is displayed by the virtual or augmented reality display. The virtual space includes a three-dimensional target object; at least one plane, including a tracking plane, the tracking plane corresponding to the surface; and a virtual stylus in a virtual reality view, or the physical stylus in an augmented reality view. A position of the virtual stylus or the physical stylus relative to the tracking plane is correlated to an actual position of the physical stylus relative to the surface; and a cross-section of the target object is displayed on the tracking plane where the tracking plane intersects the target object.

Abstract: The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.

Abstract: The disclosure relates to modified vaccinia virus vectors derived from the Copenhagen strain of vaccinia virus, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified Copenhagen-derived vaccinia virus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Abstract: Provided are compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided.

Abstract: There are provided compositions and methods for modulating stem cell division decisions, in particular, division symmetry. It has been demonstrated that wnt7a acts through frizzled-7 receptor expressed on the surface of adult stem cells, e.g. satellite stem cells, to activate the planar cell polarity (PCP) pathway, thereby promoting symmetrical expansion of stem cells. The compositions and methods of the invention are useful, for example, in modulating stem cell division symmetry in vitro and in vivo, in replenishing and expanding the stem cell pool, and in promoting the formation, maintenance, repair and regeneration of tissue.

Abstract: A recombinant adeno-associated virus (rAAV) particle with a mutated capsid protein is provided. In particular, the present disclosure provides methods of delivering a therapeutic agent to a muscle, airway, liver, central nervous system, retina or lung cell in a subject, and methods of treating or preventing infectious, acquired or genetic disease, with said rAAV particle.

Abstract: Provided are compounds of Formula (II) that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided.

Abstract: Provided herein are methods for enhancing infection, growth, spread, or titer of an oncolytic RNA virus in a cancer or tumor cell; enhancing the oncolytic activity, cytokine-induced cell death activity, and/or cytotoxic activity of an oncolytic RNA virus in a cancer or tumor cell; upregulating cytokine response to, and/or enhancing the immunotherapeutic activity of an oncolytic RNA virus in a cancer or tumor cell; and/or treating a tumor or cancer in a subject in need thereof. Such methods employ a vanadium-containing compound, administered to the cancer or tumor cells before, after, or concurrently with infection of the cancer or tumor cells with the oncolytic RNA virus. Related compositions, uses, and kits therefor are also provided. Methods for producing RNA viruses, RNA virus-based cancer vaccines, and RNA virus-based cancer gene therapy vectors are also provided.

Abstract: A system and method are provided that employ the variability of physiological waveforms to estimate the time to death after WLST, or time to inadequate organ perfusion. From the variability data one can derive an index subsequently used to determine the probability of death (or inadequate organ perfusion) within a given time frame in an automated fashion from bedside monitors in the intensive or post-anesthesia care unit. The resulting variability index can also be combined with the clinical variables used in other death prediction tools to enhance the performance and outcome when compared to existing models. In at least one implementation, variability monitoring at the bedside could be used to provide estimates of the probability that a patient will die within a certain time frame after WLST. These estimates could be used to reduce the distress of the patients' families, as well as optimize the use of resources surrounding donation.