Abstract: The present invention relates to useful methods of treating Acute Myeloid Leukemia (AML) in a human. in the presence of gene mutations.

Abstract: A guide structure (10) is configured for placement on a patient's skin and holding a medical probe (61) for adjustable positioning over the patient's skin during vascular line placement. A preferred guide structure includes a U-shaped base (12) having two arms (14, 16) separated by an open space (18). A carriage (50) for a medical probe holder (60) is movable along carriage guide surfaces (40, 42) of the arms of the base and thereby forms a movable bridge spanning the open space. The medical probe holder carrying a medical probe is movable in a direction transverse to the arms of the base to set the medical probe to a desired distance into the open space. A carriage translation actuator (62) operatively associated with the carriage enables movement of the carriage and thereby adjusts the position of the medical probe over the surface of the patient's skin.

Abstract: Disclosed are systems and methods for generating wide-field optical coherence tomography angiography (OCTA) images. In embodiments, multiple OCTA scans of a sample are automatically acquired at overlapping locations. The systems and methods include functionality to adaptively control the scanning procedure such that eye blink and eye motion events are detected in real time and accounted for during 3D scan acquisition. Also disclosed are methods for detecting and correcting motion-related artifacts in OCTA datasets which allow for the longer scan times over larger fields of view required for wide-field imaging. These methods may include division of en face angiogram images into a set of motion-free parallel strips, and application of gross and fine registration methods to align overlapping strips into a motion-corrected composite image. A series of overlapping motion-corrected composite images may be combined into a larger montage to enable wide-field OCTA imaging using multiple OCTA scans.

Abstract: A nanoparticle for delivering an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor to a subject and methods for treating inflamed tissue in a subject using the nanoparticle.

Abstract: An example system for estimating a hydration level of an individual can include: a mechanism configured to apply mechanical pressure to a digit of the individual; an light detector configured to sense the light from the digit; and a controller programmed to perform functions including: send a first signal to the mechanism to apply the mechanical pressure to the digit; send a second signal to the mechanism to release the mechanical pressure on the digit; determine a capillary refill time based upon a third signal from the light detector indicating an amount of time for capillaries of the individual to refill with blood; and estimate the hydration level of the individual based upon the capillary refill time and one or more additional parameters.

Abstract: Disclosed herein are methods and systems for capillary oximetry (e.g., retinal capillary oximetry) using optical coherence tomography (OCT). The method may include obtaining an OCT angiography dataset, performing capillary segmentation based on the OCT angiography dataset to obtain capillary segments, resampling, registering, and/or averaging B-scans of the OCT angiography dataset that correspond to a first capillary segment of the capillary segments to obtain an averaged B-scan for the first capillary segment, determining an anterior and posterior border of the first capillary segment, and determining an oxygen saturation of the first capillary segment based on the averaged B-scan, the anterior border, and the posterior border. Other embodiments may be described and claimed.

Abstract: Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative disorders using those pharmaceutical compositions.

Abstract: Methods of treating neuroinflammation in a subject by administering to the subject an agent that inhibits activation of coagulation factor XI (FXI), inhibits the activity of activated FXI (FXIa), or reduces expression of FXI are described. The agent that inhibits activation of FXI can be a monoclonal antibody specific for FXI, such as a monoclonal antibody having the complementarity determining region (CDR) sequences of anti-FXI antibody 14E11. Small molecule inhibitors and antisense compounds directed to FXI or FXIa are also contemplated as agents that inhibit activity of FXIa or reduce expression of FXI. The neuroinflammation in the subject can be associated with any one of a number of different diseases or disorders, such as an autoimmune disease of the central nervous system (CNS) or a neurodegenerative disease.

Abstract: Provided are substituted 8-methylquinazolin-4(3H)-one compounds useful as PARP inhibitors for the treatment of cancer and asthma, as well as pharmaceutical compositions comprising them and methods for their synthesis.

Abstract: The present disclosure relates generally to dis-arming immune cell product sensitivity to androgens. Provided herein are methods, systems, and compositions for disarming androgen receptor (AR) activity in immune cells, for instance in the context of CAR-T cell therapy, allogenic T cell therapy, DC vaccines, macrophage therapy, myeloid/macrophage antigen receptor therapy, NK cell therapy, and so forth. Different methods for reducing AR function are described.

Abstract: Disclosed herein are therapeutic constructs including a delivery particle, at least one anti-cancer agent (e.g., a mitotic kinase inhibitor), and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.

Abstract: Monoclonal antibodies that bind, such as specifically bind, blood protein factor XII (FXII) are described. The monoclonal antibodies (including antigen-binding fragments thereof) are capable of forming immune complexes with human FXII and inhibiting FXII activity, resulting in safe anti-inflammatory and anti-thrombotic effects.

Abstract: Provided herein are libraries of nerve-specific fluorescent contrast agents of substituted 8-methyl-phenoxazine compounds of Formula (I) with excitation and emission profile comparable to US FDA approved methylene blue (MB) and indocyanine green (ICG), respectively, allowing for real-time intraoperative imaging using clinical-grade surgical systems. Also provided 700 nm lead candidates with substantially improved water-solubility, fully negating the need for formulation development with the added advantage of improved safety profiles for patient use in the clinic as well as decreased overall cost of clinical translation.

Abstract: Provided are near-infrared nerve-sparing fluorescent compounds, compositions comprising them, and methods of their use in medical procedures.

Abstract: Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V: R1—X1—X2—(X3)n—X4—X5—X6—X7—R2?? Formula I R1-Asn-Val-Ser-Ala-Tyr-Pro-Thr-R2?? Formula V. Also disclosed are conjugates and compositions comprising the peptides. The compositions may comprise a desired agent to be delivered to the retina, such as a therapeutic agent and/or an imaging agent. Methods for administering the peptide, conjugates, and/or composition to a subject also are disclosed.

Abstract: The present disclosure provides the use of inhibitor(s) of an activity of HMG-CoA reductase (HMGCR) (a statin) to reduce and/or prevent future metastasis and prolong survival inpatients diagnosed with melanoma, for instance determined to be at high-risk of melanoma progression, such as melanoma metastasis. Also disclosed are methods for treating patients with a statin. Optionally, described methods involve measurement of a gene expression profile signature in the primary melanoma.

Abstract: Various embodiments herein provide methods to obtain corneoscleral surface profiles from optical coherence tomography (OCT) data and/or another three-dimensional (3D) volumetric scan of the eye. The OCT data may be obtained using radial scans. The limbal junction may be estimated from the radial profiles of the central moments of OCT axial scans. The external topographic limbus may be located using curve fitting of a scleral topography map and/or corneal topography map. Elevation profiles and topographic maps of the anterior eye, referenced to the best-fit topographic limbal circle and its associated plane and central axis, are constructed. The reference coordinate allows the generation of maps and radial profiles for surface elevation, axial radius, and tangential radius. Using ellipsoidal fitting, the corneal height, corneal principal meridians and associated radii of curvature, and scleral principal meridians and associated radii of curvature, are calculated.

Abstract: The present invention concerns phthalazinone-based compounds of that inhibit the PARP-1 protein, the compounds having Formula (I):

Abstract: Disclosed are methods for performing transcription-dependent directed evolution (TRADE) and novel AAV capsids selected using such methods.

Abstract: Disclosed are methods for performing transcription-dependent directed evolution (TRADE) and novel AAV capsids selected using such methods.