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 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: 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: 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.

Abstract: Provided are methods of treating diabetes and/or obesity in a subject in need thereof, and methods of increasing the amount of cholic acid-7-sulfate (CA7S) in a subject. Further provided herein are methods of administering CA7S to a subject. Also provided are compositions and kits comprising cholic acid-7-sulfate, or a salt thereof for use in the treatment of diabetes and/or obesity.

Abstract: The systems and methods described herein determine metrics of cardiac performance via a mechanical circulatory support device and use the cardiac performance to calibrate, control and deliver mechanical circulatory support for the heart. The systems include a controller configured to operate the device, receive inputs indicative of device operating conditions and hemodynamic parameters, and determine vascular performance, including vascular resistance and compliance, and native cardiac output. The systems and methods operate by using the mechanical circulatory support device (e.g., a heart pump) to introduce controlled perturbations of the vascular system and, in response, determine heart parameters such as stroke volume, vascular resistance and compliance, left ventricular end diastolic pressure, and ultimately determine native cardiac output.

Abstract: The present disclosure provides, inter alia, anti-peripheral lymph node addressin antibodies and antigen binding fragments thereof. The present disclosure also provides compositions comprising drug-containing polymeric particles that mimic lymphocyte migration in vivo and can specifically deliver immunosuppressive or immunoregulatory drugs to lymphoid tissues and sites of chronic inflammation where T-cell activation and T-cell mediated injury are occurring; such compositions comprise the antibodies or antigen-binding fragments thereof described in the disclosure. The present disclosure also comprises antibody-drug conjugates and compositions comprising the antibody-drug conjugates. Methods of preparing and using these antibodies, antigen-binding fragments thereof, and compositions thereof are also provided.

Abstract: A system comprises an ultrasound subsystem and a magnetic resonance imaging (MRI) subsystem. The ultrasound subsystem applies pulses of focused ultrasound having one or more parameters to an identified location in a subject that is to receive treatment. The parameters are determined in accordance with a magnetic resonance guided focused ultrasound (MRgFUS) treatment plan. The MRI subsystem acquires functional image data corresponding to the identified location concurrently with the applied pulses of focused ultrasound. The MRI subsystem obtains a reconstructed series of functional images of the subject using the functional image data. The functional images are indicative of a first region within the identified location in which neuronal activity has been modified by the applied pulses. The system is configured to adjust one or more parameters of the MRgFUS treatment plan using the reconstructed series of functional images.