The present invention provides a sensor for detecting a bioanalyte, comprising: a substrate; a pair of terminal electrodes disposed on the substrate in mutually spaced apart and opposing relation; and a non-insulating sensing element applied to a surface of the substrate, between and in electrical contact with the pair of terminal electrodes wherein the sensing element provides a conduction path between the terminal electrodes, wherein the sensing element comprises an oxygen-deficient metal oxide layer and a bioanalyte binding site, and wherein when a voltage is applied across the sensor, an electrical signal is generated that is proportional to a change in conductance of the sensing element corresponding to binding of a bioanalyte to the bioanalyte binding site.

The present invention provides a sensor for detecting a bioanalyte, comprising: a substrate; a pair of terminal electrodes disposed on the substrate in mutually spaced apart and opposing relation; and a non-insulating sensing element applied to a surface of the substrate, between and in electrical contact with the pair of terminal electrodes wherein the sensing element provides a conduction path between the terminal electrodes, wherein the sensing element comprises an oxygen-deficient metal oxide layer and a bioanalyte binding site, and wherein when a voltage is applied across the sensor, an electrical signal is generated that is proportional to a change in conductance of the sensing element corresponding to binding of a bioanalyte to the bioanalyte binding site.

The present invention relates to a method aiding in the assessment of rheumatoid arthritis (“RA”). The method is used in assessing RA in vitro. It is practiced by analyzing biochemical markers, comprising measuring the concentration of anti-CCP and anti-PIK3CD and correlating the concentrations determined to the absence or presence of RA. The invention also relates to the use of a marker panel comprising anti-CCP and anti-PIK3CD in the diagnosis of RA and it teaches a kit for performing the method of the invention. Further the invention relates to the use of a marker panel comprising anti-CCP and anti-PIK3CD to differentiate RA from other autoimmune diseases, preferably osteoarthritis (OA).

The present invention relates to a method aiding in the assessment of rheumatoid arthritis (“RA”). The method is used in assessing RA in vitro. It is practiced by analyzing biochemical markers, comprising measuring the concentration of anti-CCP and anti-PIK3CD and correlating the concentrations determined to the absence or presence of RA. The invention also relates to the use of a marker panel comprising anti-CCP and anti-PIK3CD in the diagnosis of RA and it teaches a kit for performing the method of the invention. Further the invention relates to the use of a marker panel comprising anti-CCP and anti-PIK3CD to differentiate RA from other autoimmune diseases, preferably osteoarthritis (OA).

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 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 present invention relates to a method for diagnosing Sézary syndrome or mycosis fungoides in a subject. The present invention further relates to a method for determining the frequency of Sézary signature cells and/or mycosis fungoides cells in a sample. Further, the present invention relates to a computer-implemented method comprising a classifier algorithm to determine the frequency of Sézary signature cells and/or mycosis fungoides cells. In addition the present invention relates to a panel of biomarkers that can be used for the diagnosis of Sézary syndrome or mycosis fungoides.

The present invention relates to a method for diagnosing Sézary syndrome or mycosis fungoides in a subject. The present invention further relates to a method for determining the frequency of Sézary signature cells and/or mycosis fungoides cells in a sample. Further, the present invention relates to a computer-implemented method comprising a classifier algorithm to determine the frequency of Sézary signature cells and/or mycosis fungoides cells. In addition the present invention relates to a panel of biomarkers that can be used for the diagnosis of Sézary syndrome or mycosis fungoides.

The invention is based on the identification of the intracellular kinase calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key checkpoint inhibitor in tumour cells mediating resistance against cytotoxic T lymphocytes (CTL). CAMK1D was identified in PD-L1 refractory tumours to impair CTL-induced death receptor signalling and apoptosis via caspase inhibition. The invention offers therapeutic approaches involving impairing CAMK1D immune checkpoint function by various CAMK1D inhibitors, especially nucleic acid or small molecule inhibitors of CAMK1D and/or treatments involving CAMK1D inhibitors with death receptor agonists. The medical approaches of the invention are useful for treating subjects suffering from various proliferative disorders; preferably such proliferative disorders that are characterized by a resistance to CTL mediated immune responses, or which are refractory or resistant to treatments with other immune checkpoint therapies, such as PD1-PDL1 antagonistic treatments. Provided are the medical applications and corresponding diagnostic approaches, kits, CAMK1D inhibitors and screening methods for the identification of new therapeutic agents for the treatment of proliferative disorders.

The invention is based on the identification of the intracellular kinase calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key checkpoint inhibitor in tumour cells mediating resistance against cytotoxic T lymphocytes (CTL). CAMK1D was identified in PD-L1 refractory tumours to impair CTL-induced death receptor signalling and apoptosis via caspase inhibition. The invention offers therapeutic approaches involving impairing CAMK1D immune checkpoint function by various CAMK1D inhibitors, especially nucleic acid or small molecule inhibitors of CAMK1D and/or treatments involving CAMK1D inhibitors with death receptor agonists. The medical approaches of the invention are useful for treating subjects suffering from various proliferative disorders; preferably such proliferative disorders that are characterized by a resistance to CTL mediated immune responses, or which are refractory or resistant to treatments with other immune checkpoint therapies, such as PD1-PDL1 antagonistic treatments. Provided are the medical applications and corresponding diagnostic approaches, kits, CAMK1D inhibitors and screening methods for the identification of new therapeutic agents for the treatment of proliferative disorders.