Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: A method that provides a graphical indication of whether a patient will have cancer recurrence uses univariate and bivariate prognostic features that were generated as part of a minimal spanning tree (MST). The method determines the values of first and second features. A first value is measured by detecting objects in an image of tissue from the cancer patient stained with a protein-specific IHC biomarker. A second value is measured using objects marked with an mRNA-specific probe biomarker detected in the tissue. The first feature is the univariate prognostic feature for cancer recurrence in a cohort of cancer patients. A combination of the first and second features is the bivariate prognostic feature for cancer recurrence in the cohort. The first and second features are elements of the MST. Nodes of the MST represent the univariate features, edges represent the bivariate features, and edge weights represent prognostic significance of bivariate features.

Abstract: A method is provided for lowering blood pressure in a subject in need thereof by administering an angiotensin II receptor blocker pharmaceutical composition to a subject qualified for over-the-counter access to the angiotensin II receptor blocker pharmaceutical composition. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition includes azilsartan medoxomil, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition comprises an active ingredient that is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2?-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are triazalone compounds of Formula (I): and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be useful as adenosine receptor antagonists, for example in the treatment of diseases or conditions mediated by the adenosine receptor, such as cancer, movement disorders, or attention disorders.

Abstract: Combinations of an apyrase and an annexin, including fusion proteins thereof, are synergistic antithrombotics that do not induce unwanted bleeding

Abstract: The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.

Abstract: The invention relates to a novel inhibitor pharmacophore of PCSK9 and heteroaryl compounds that bind the PCSK9 protein.

Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: A convolutional neural network predicts which regions of a tissue slice would be stained by a first stain by training a model to identify those regions based only on tissue stained by a second stain. Thereafter the first stain need not be used to mark cancerous regions on other tissue slices that are stained with the second stain. The training slice is stained with a first immunohistochemical stain and a second counterstain. A target region of an image of the training slice is identified using image analysis based on the first stain. A set of parameters for associated mathematical operations are optimized to train the model to classify pixels of the image as belonging to the target region based on the second stain but not on the first stain. The trained parameters are stored in a database and applied to other images of tissue not stained with the first stain.

Abstract: The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and n have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use as anti-proliferative and/or cell-killing agents.

Abstract: Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure relates, in general, to therapeutic combinations of acalabrutinib and capivasertib, and to corresponding methods of treatment, pharmaceutical compositions, and kits.

Abstract: The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

Abstract: A method is provided for lowering blood sugar in a subject in need thereof by administering a biguanide anti-hyperglycemic pharmaceutical composition to a subject qualified for over-the-counter access to the biguanide anti-hyperglycemic pharmaceutical composition. In some embodiments, the biguanide anti-hyperglycemic pharmaceutical composition includes N,N-dimethylimidodicarbonimidic diamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the biguanide anti-hyperglycemic pharmaceutical composition includes metformin hydrochloride.

Abstract: A method is provided for lowering blood sugar in a subject in need thereof by administering a gliflozin Sodium-Glucose Cotransport 2 inhibitor pharmaceutical composition to a subject qualified for over-the-counter access to the gliflozin Sodium-Glucose Cotransport 2 inhibitor pharmaceutical composition. In some embodiments, the gliflozin Sodium-Glucose Cotransport 2 inhibitor pharmaceutical composition includes empagliflozin, canagliflozin, and ertugliflozin. In some embodiments, the gliflozin Sodium-Glucose Cotransport 2 inhibitor pharmaceutical composition includes (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol or a pharmaceutically acceptable salt thereof.

Abstract: The disclosure relates to methods and compositions for the treatment of lupus nephritis. Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.

Abstract: The disclosure relates to methods and compositions for the treatment of type I IFN mediated disease. Specifically, the disclosure relates to a subcutaneous dose of a type I IFN receptor inhibitor.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: The immunostimulatory effect of lipid nanoparticles (LNPs) continues to block their use for safe and effective delivery of pharmaceutical drugs. Consequently, there exists a need to develop effective LNP delivery systems with an increased therapeutic window that do not trigger an inflammatory response. Disclosed herein are lipid nanoparticles comprising a lipid phase and at least one lipophilic anti-inflammatory agent, and pharmaceutical compositions comprising lipid nanoparticles and methods for using lipid nanoparticles. The anti-inflammatory lipid nanoparticles disclosed herein may further serve as platforms for selective delivery of, for example, nucleic acid segments to target cells and tissues, such as antisense oligonucleotides, DNA, mRNAs, siRNAs, Cas9-guideRNA complex.