The present invention is based on the discovery that three proteins, Cystatin B, Chaperonin 10, and Profilin are present in the urine of patients with bladder cancer, a cancer of epithelial origin. Accordingly, the present invention is directed to methods for prognostic evaluation of cancers of epithelial origin and to methods for facilitating diagnosis of cancers of epithelial origin by monitoring the presence of these markers in biological samples. The invention is also directed to markers for therapeutic efficacy.

Provided are a method of simply detecting Alzheimer's disease (AD) and a method of simply stratifying AD pathological phases, and a reagent that can be used for the methods, based on the fact that measurement of a protein contained in extracellular vesicles enables detection of Alzheimer's disease and stratification of AD pathological phases.

The disclosure provides biomarker proteins, a change in the concentration or activity level of which are associated with atypical hemolytic uremic syndrome (aHUS) or clinically meaningful treatment of aHUS with a complement inhibitor. Also provided are compositions and methods for interrogating the concentration and/or activity of one or more of the biomarker proteins in a biological fluid. The compositions and methods are useful for, among other things, evaluating risk for developing aHUS, diagnosing aHUS, determining whether a subject is experiencing the first acute presentation of aHUS, monitoring progression or abatement of aHUS, and/or monitoring response to treatment with a complement inhibitor or optimizing such treatment.

The present invention relates to a method for monitoring Cathepsin S inhibitor activity in tissue samples of animals comprising: a) providing a tissue sample of an animal to whom a Cathepsin S inhibitor has been administered or providing a tissue sample of an animal that was contacted in vitro with a Cathepsin S inhibitor, wherein the tissue samples comprise white blood cells, b) measuring li p10 peptide level in white blood cells of the tissue sample of step a) by flow cytometry and c) correlating li p10 peptide level in white blood cells to Cathepsin S inhibitor dose, wherein a Cathepsin S inhibitor leads to increased level of li p10 peptide in the white blood cells.

A use of vivapain-4 (VX-4), which is a cysteine protease of Plasmodium vivax, showing pH-dependent switching of substrate specificity, is provided. More specifically, a method of treating a parasitic disease caused by Plasmodium vivax by inhibiting VX-4; a method of screening a protease inhibitor acting on VX-4, wherein the protease inhibitor is useful as an anti-malarial agent acting on Plasmodium species, for example, Plasmodium vivax; and a method of identifying the activity of VX-4, are provided.

The disclosure provides biomarker proteins, a change in the concentration or activity level of which are associated with atypical hemolytic uremic syndrome (aHUS) or clinically meaningful treatment of aHUS with a complement inhibitor. Also provided are compositions and methods for interrogating the concentration and/or activity of one or more of the biomarker proteins in a biological fluid. The compositions and methods are useful for, among other things, evaluating risk for developing aHUS, diagnosing aHUS, determining whether a subject is experiencing the first acute presentation of aHUS, monitoring progression or abatement of aHUS, and/or monitoring response to treatment with a complement inhibitor or optimizing such treatment.

The present invention is based on the discovery that three proteins, Cystatin B, Chaperonin 10, and Profilin are present in the urine of patients with bladder cancer, a cancer of epithelial origin. Accordingly, the present invention is directed to methods for prognostic evaluation of cancers of epithelial origin and to methods for facilitating diagnosis of cancers of epithelial origin by monitoring the presence of these markers in biological samples. The invention is also directed to markers for therapeutic efficacy.

The disclosure provides biomarker proteins, a change in the concentration or activity level of which are associated with atypical hemolytic uremic syndrome (aHUS) or clinically meaningful treatment of aHUS with a complement inhibitor. Also provided are compositions and methods for interrogating the concentration and/or activity of one or more of the biomarker proteins in a biological fluid. The compositions and methods are useful for, among other things, evaluating risk for developing aHUS, diagnosing aHUS, determining whether a subject is experiencing the first acute presentation of aHUS, monitoring progression or abatement of aHUS, and/or monitoring response to treatment with a complement inhibitor or optimizing such treatment.

Methods for monitoring lung inflammation status of a subject suffering from a respiratory disorder comprise determining levels of at least three markers in urine samples taken from the subject at multiple time points, wherein increased levels of at least one of the markers in a urine sample is indicative of or predictive of a pulmonary exacerbation and/or wherein decreased levels of at least one of the markers in a urine sample following an increase are indicative or predictive of recovery from, or successful treatment of, a pulmonary exacerbation, wherein at least one of the markers is selected from RNASE3, Periostin, Siglec 8, chitinase-3-like protein (C3L1) and cathepsin B. Corresponding systems, test kits and computer programs are provided.

Provided are paper-based microfluidic devices for measurement of cystatin C in a biological sample, such as blood or a blood fraction, and methods for fabricating such devices. Also provided are methods of detecting cystatin C in a biological fluid sample to diagnose or monitor a chronic kidney disease.