Abstract: As described herein, chromosomal missegregations, chromosomal micronuclei, cytosolic DNA, and combinations thereof are indicative of metastatic cancer. Methods and compositions are described herein that are useful for detection and treatment of patients with chromosomal instabilities such as chromosomal missegregations, chromosomal micronuclei, cytosolic DNA, and combinations thereof. For example, some of the methods and compositions include use of kinesin-13 proteins such as Kif2b, MCAK/Kif2c, or KIF13A. The methods and compositions can also include inhibitors of STING, ENPP1, cGAS, NF-kB transcription factor p52, NF-kB transcription factor RelB, or any combination thereof. Methods are also described for identifying compounds that are effective for treatment of cancer, including metastatic cancer.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.

Abstract: Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclosure describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons.

Abstract: The present disclosure is directed to systems and methods for identifying regions of interest (ROIs) in images. A computing system may identify an image including an annotation defining an ROI. The image may have a plurality of pixels in a first color space. The computing system may convert the plurality of pixels from the first color space to a second color space to differentiate the annotation from the ROI. The computing system may select a first subset of pixels corresponding to the annotation based at least on a color value of the first subset of pixels in the second color space. The computing system may identify a second subset of pixels included in the ROI from the image using the first subset of pixels. The computing system may store an association between the second subset of pixels and the ROI defined by the annotation in the image.

Abstract: The present disclosure is directed to systems and methods for classifying biomedical images. A feature classifier may generate a plurality of tiles from a biomedical image. Each tile may correspond to a portion of the biomedical image. The feature classifier may select a subset of tiles from the plurality of tiles by applying an inference model. The subset of tiles may have highest scores. Each score may indicate a likelihood that the corresponding tile includes a feature indicative of the presence of the condition. The feature classifier may determine a classification result for the biomedical image by applying an aggregation model. The classification result may indicate whether the biomedical includes the presence or lack of the condition.

Abstract: The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.

Abstract: Described herein are systems and methods of processing immobilization molds for application of treatment, A computing system may generate a three-dimensional mold model of immobilization mold within with a subject is to be positioned for application of a treatment. The computing system may subtract a three-dimensional scan of at least a portion of the subject from the three-dimensional mold model to define an opening therein. The computing system may remove, from the three-dimensional mold model, a first portion to define an imprint in the opening from a first axis along which the subject is to enter. The computing system may remove, from a second portion of the three-dimensional mold model remaining with the removal of the first portion, inward protrusions into the imprint of relative to the second axis intersecting the first axis.

Abstract: The present invention relates to a method of identifying epigenetic reprogramming. Identifying epigenetic reprogramming comprises detecting large organized heterochromatin lysine (K)-9 modified domains (LOCKs) and large DNA hypomethylated blocks in a sample containing DNA from a subject having cancer, for example, PDAC.

Abstract: Disclosed is three-dimensional interferometric lattice light-sheet (3D-iLLS) imaging, an approach that overcomes limitations of prior microscopy techniques. 3D-iLLS provides, by virtue of selective-plane illumination (SPIM), low light levels and photobleaching, while providing increased background suppression and significantly improved volumetric imaging/sectioning capabilities through 4Pi interferometry. An example setup demonstrated 3D-iLLS with axial resolution and single-particle localization precision down to <100 nm (FWHM) and <10 nm (1?), respectively. 3D-iLLS enables a fuller elucidation of sub-cellular phenomena by enhanced 4D resolution and improved SNR during live imaging.

Abstract: The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into cortical neurons, and cortical neurons generated by such methods. The presently disclosed subject matter also provides for uses of such cortical neurons for treating neurodegenerative CNS disorders.

Abstract: The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK?) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

Abstract: The presently disclosed subject matter provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) that specifically target human mesothelin, and immunoresponsive cells comprising such CARs. The presently disclosed mesothelin-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present disclosure discusses systems and methods to detect blur in digital images. The solution can be incorporated into the quality control systems of pathology and other slide scanners or can be a stand-alone solution. The solution can identify scanned images that include blur and cause the scanner to automatically rescan the blurry image. The solution can also identify regions of the scanned image that include blur. The solution can generate blur maps for each of the scanned images that identify regions of the scanned image that include blur.

Abstract: The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-36. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.

Abstract: Presented herein are systems and methods of clustering images using encoder-decoder models. A computing system may identify tiles derived from an image. Each tile may have a first dimension. The computing system may apply an image reconstruction model to the tiles. The image reconstruction model may include an encoder block having a first set of weights to generate embedding representations corresponding to the tiles. Each embedding representation may have a second dimension lower than the first dimension. The image reconstruction model may include a decoder block having a second set of weights to generate reconstructed tiles corresponding to the embedding representations. The computing system may apply a clustering model comprising a feature space to the embedding representations to classify each tile to one of a plurality of conditions.

Abstract: The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

Abstract: Presented herein are systems and methods of classifying biomedical images. A computing system may identify a first plurality of tiles from a first biomedical image of a first sample. The computing system may determine a first category for the first sample by applying the plurality of tiles to a classification model. The classification model may include a tile encoder to determine, based on the first plurality of tiles, a corresponding plurality of feature vectors in a feature space. The classification model may include a clusterer to select a subset of feature vectors from the plurality of feature vectors based on a plurality of centroids defined in the feature space. The classification model may include an aggregator to generate, based on the subset of feature vectors, the first category for the sample. The computing system may store an association between the first category and the first biomedical image.

Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Abstract: Disclosed herein are methods and compositions for identifying transcriptional and epigenetic age-related markers. Disclosed herein are also methods and compositions for reprogramming cell age by modulating transcriptional and epigenetic age-related markers identified herein. The identified transcriptional and epigenetic age-related markers can also be used for measuring cellular age in a cell or tissue.