A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13Rα2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in a subject. The methods and compositions involve measurement of at least one of proteins: IL-16, IL-7, VEGF, CXCL9, CX3CL1, CCL24, CCL19, and CCL11 in a body fluid sample of a subject suspected of having CFS/ME. Levels of one or more of the aforementioned proteins can be used to facilitate a diagnosis of a CFS/ME and/or confirm a diagnosis of CFS/ME. The methods and compositions of the present disclosure also find use in screening subjects for clinical trials and facilitating treatment decisions for a subject.

The invention relates to methods of treating a patient suffering from an IL-33-mediated disorder, such as asthma, comprising administering to the patient an IL-33 axis binding antagonist based on the genotype of the /L1RL1gene, the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2. The invention further relates to methods of determining whether a patient is at increased risk of an IL-33-mediated disorder, as well as methods of determining whether a patient suffering from such a disorder is likely to respond to a treatment comprising an IL-33 axis binding antagonist, based on the genotype of the /L1RL1gene the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2.

The invention relates to in vitro methods for detecting bacteremia, for selecting a therapy for a subject with cystic fibrosis or for a subject with systemic inflammatory response syndrome and for selecting a subject with cystic fibrosis or with systemic inflammatory syndrome for a particular therapy based on the expression levels of a gene selected from tumor necrosis factor alpha (TNFα), IL-1b, IL-10, CCL2, interferon beta (IFN-β), IL-17, IL-2, IL-4 and VEGF in a blood sample from the subject. The invention also relates to a kit comprising a TLR-4 agonist and a reagent specific for determining the level of at least one cytokine selected from the group consisting of tumor necrosis factor alpha (TNFα), IL-1b, IL-10, CCL2, interferon beta (IFN-β), IL-17, IL-2, IL-4 and VEGF and to the uses of this kit.

Provided herein are assays that provide digital measurement methods to detect proteins and other biomolecules, e.g., at low- to mid-attomolar concentrations.

Disclosed are an IL-5 binding molecule, and a preparation method and use thereof. The binding molecule includes the following complementarity determining regions: an amino acid sequence of CDR1 selected from any one of sequences as set forth in SEQ ID NOs. 43-49; an amino acid sequence of CDR2 selected from any one of sequences as set forth in SEQ ID NOs. 50-56; and an amino acid sequence of CDR3 selected from any one of sequences as set forth in SEQ ID NOs. 57-62. The binding molecule is capable of specifically binding to IL-5, and effectively blocking the cell proliferation induced by IL-5.

Provided are a method of efficiently producing an sIL-2R antigen in an amount necessary for antibody generation, and a method of producing an anti-sIL-2R antibody using the antigen. Specifically, provided are a method of producing soluble interleukin-2 receptor, including culturing SCC-3 cells and recovering soluble interleukin-2 receptor from a culture of the cells, and a method of producing an anti-soluble interleukin-2 receptor antibody, including immunizing an animal with sIL-2R produced by the method.

The present disclosure pertains to predicting an onset of a cerebral hemorrhagic event in a subject by testing a blood sample of the subject for the presence or absence of one or more indicators; and correlating the presence or absence of the one or more indicators to the subjects risk for suffering from the cerebral hemorrhagic event, where the presence of the one or more indicators is correlated to an increased risk in the subject for suffering from the cerebral hemorrhagic event and where the absence of the one or more indicators is correlated to a decreased risk in the subject for suffering from the cerebral hemorrhagic event. The methods of the present disclosure may also include implementing a therapeutic decision in order to prevent the cerebral hemorrhagic event. The present disclosure also pertains to kits for use in predicting an onset of a cerebral hemorrhagic event in a subject.

Methods for treating coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, is described. The methods can be used to reduce the severity of outcomes related to COVID-19, such as hospitalization and ventilation. For example, treatment of a subject with a therapeutic agent that neutralizes interleukin 13 (IL-13) can result in reduced risk for mechanical ventilation in the subject. Also described are methods of predicting risk of mechanical ventilation in subjects with COVID-19.

The invention provides compositions, formulations, and methods for treatment of malignancies via activation of an inflammatory response in the subject. Such compositions, formulations, and methods for are preferably used in conjunction with other therapies for the treatment and/or management of malignancies, e.g., chemotherapy and/or radiation. The invention also provides methods of monitoring immune activation in subjects with malignancies.