Abstract: A device configured to be implanted in a subject includes a sensing module, a therapeutic module, and a battery. The sensing module includes at least two of an accelerometer, an electrocardiogram (ECG) sensor, a photoplethysmogram (PPG) sensor, and a temperature sensor. The therapeutic module includes a drug reservoir and a reciprocating pump. The battery powers the sensing module and the therapeutic module. The sensing module is configured to detect a biological event in the subject and, upon detection of the biological event, send a signal to the therapeutic module. The therapeutic module is configured to receive the signal from the sensing module and, upon receiving the signal, administer a drug to the subject from the drug reservoir via the pump.

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. 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. In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent.

Abstract: Aspects of the disclosure relate to compositions and methods for targeted protein degradation. In some embodiments, the disclosure relates to methods of evolving protein degrons to interact with certain small molecule inducers (e.g., VS-777, PT-179, or PK-1016). In some embodiments, the disclosure relates to compositions (e.g., peptides, nucleic acids encoding the protein degrons, etc.) used for targeted protein degradation. In some embodiments, the disclosure relates to methods of degrading a target polypeptide in a cell.

Abstract: Systems and methods are provided for augmenting digital analysis of lesions. An image of tissue having a glandular epithelial component is generated. The image represents a plurality of medium-scale epithelial components. For each of a plurality of cells within the image, a representative point is identified to provide a plurality of representative points for each of the plurality of medium-scale epithelial components. For each of a subset of the plurality of medium-scale epithelial components, a graph connecting the plurality of representative points is constructed. A plurality of classification features is extracted for each of the subset of medium-scale epithelial components from the graph constructed for the medium-scale epithelial component. A clinical parameter is assigned to each medium-scale epithelial component according to the extracted plurality of classification features.

Abstract: Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module.

Abstract: Systems and methods are provided for determining if a subject has a biological condition from a dried fluid sample. A fluid sample from a subject is dried in a microfluidic device to provide a dried fluid sample. The dried fluid sample is imaged at a camera to provide a sample image, and the sample image is provided to a computer vision mode. At the computer vision model, it is determined if the sample image contains a ferning pattern indicative of a biological condition of the subject.

Abstract: The present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.

Abstract: Systems and methods can quantify the tumor microenvironment for diagnosis, prognosis and therapeutic response prediction by fusing different data types (e.g., morphological information from histology and molecular information from omics) using an algorithm that harnesses deep learning. The algorithm employs tensor fusion to provide end-to-end multimodal fusion to model the pairwise interactions of features across multiple modalities (e.g., histology and molecular features) and deep learning. The systems and methods improve upon traditional methods for quantifying the tumor microenvironment that rely on concatenation of extracted features.

Abstract: The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Abstract: Scan time in diffusion-relaxation magnetic resonance imaging (“MRI”) is reduced by implementing time-division multiplexing (“TDM”). In general, time-shifted radio frequency (“RF”) pulses are used to excite two or more imaging volumes. These RF pulses are applied to induce separate echoes for each slice. Diffusion MRI data can thus be acquired with different echo times, or alternatively with the same echo time, in significantly reduced overall scan time. Multidimensional correlations between diffusion and relaxation parameters can be estimated from the resulting data.

Abstract: Technology provided herein relates to methods of treating cancer comprising administering to a subject in need thereof a first stem cell (SC) modified to release an oncolytic virus and a second SC which is gene edited to inactivate a receptor for the oncolytic virus, thereby generating a stem cell resistant to the virus, wherein the second SC is also engineered to express an immunomodulatory polypeptide agent. Compositions comprising a first and second SC, and uses thereof, are also provided herein.

Abstract: The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to ?-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to ?-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in ?-cells.

Abstract: Insulin therapy revolutionized the care of patients with diabetes, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment for hypoglycemia; however, current dosage forms remain under-utilized due to poor patient compliance. High-density, readily soluble, and thermostable solid glucagon formulations applied with painless, application-specific microneedle-patches can treat hypoglycemia in type 1 diabetes patients who are awake or asleep. On-demand patches can prevent or treat mild hypoglycemia during the day, and enzyme-driven hypoglycemia-responsive patches can release glucagon autonomously during the night. These patches have excellent in vitro glucagon stability, loading, and release kinetics and can treat hypoglycemia in diabetic humans and animals. These delivery systems enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.

Abstract: This technology describes novel cell based combined therapeutic modalities that include a stem cell engineered to secrete a multispecific T cell engager (MiTE) polypeptide construct and an isolated population of T cells that are autologous to the subject.

Abstract: The present invention features methods for increasing sensitivity and/or reversing resistance to chemotherapy, methods for treating or preventing a cancer in a subject, methods for treating clonal hematopoiesis of indeterminate potential in a subject, and methods of identifying resistance or sensitivity to chemotherapy in a subject. In some embodiments, the methods contain the step of administering an agent that inhibits the expression or activity of a Protein phosphatase 1D (PPM1D) polypeptide or polynucleotide. The present invention also features compositions for increasing sensitivity and/or reversing resistance to chemotherapy.

Abstract: Compositions and methods relating to a panel of antigen biomarkers for the early detection of ovarian cancer. The compositions and methods encompass antigen biomarkers coupled to a substrate, with the biomarkers being selected from the group consisting of one or more of ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3.

Abstract: The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.

Abstract: Aspects of the disclosure provide nucleic acids and compositions comprising gene regulatory elements (GREs) for specific expression in nociceptor cells. Other aspects of the disclosure relate to the use of vectors and compositions comprising the gene regulatory elements for treating or managing pain and other neurological diseases in a subject in need thereof.

Abstract: A control system controls an endoscope probe in manual mode or robot mode. The system comprises a handle attached to the probe; a portable display controller connectable to the handle; a robotic controller in communication with the handle and/or the portable display controller; and a support platform to which the probe and the portable device controller are attachable according to control mode. In manual mode, the handle is detached from the platform and connected to the portable display controller such that the probe is manually navigated to a first position inside a lumen. In robot mode, the handle is attached to the platform such that the robotic controller cooperates with the handle to robotically navigate the probe to a second position inside the lumen. The portable display controller includes a control section for manipulating the probe and a display section for displaying images of the lumen acquired in both modes.

Abstract: This disclosure relates to pectin-based polymer compositions and methods of use thereof to cover, protect, and seal injuries, e.g., surgical wounds, in a mesothelial tissue. The methods include obtaining a bioadhesive pectin-based polymer composition including a complex of high-methoxyl pectin (HMP) and carboxymethylcellulose (CMC) in a ratio from about 10 to 1 to 1 to 10 by weight; applying the composition to an injured mesothelial tissue; and applying pressure for at least one minute to enable the composition to bind to the mesothelial tissue.