Method of treating hypercytokinemia by administering the CCR5/CCL5 (RANTES) interaction inhibitor maraviroc

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods of treating coronavirus infection

Provided herein are methods of preventing and treating viral infections (e.g., coronavirus infection) using a CCR5 binding agent.

HPV E6, E7 MRNA assay and methods of use thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the "In Cell HPV Assay," that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical ("LBC") cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Method of testing adequacy of cells in a specimen

The present invention relates to an appartus and method for use in pre-screening or determining the adequacy of target cells in specimen prior to conducting further diagnostic testing or analysis of the specimen. More specifically, the present invention concerns a device and method which uses light scatter techniques to detect the presence of a target cell in a specimen.

Methods and systems for predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion from a suspension sample of cervical cells

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications.

HPV E6, E7 mRNA assay and methods of use thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the In Cell HPV Assay, that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (LBC) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Methods of Assigning a COVID Pathological Type and Compositions for Practicing the Same, and Methods of Treating a Subject for Chronic COVID-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Cell specific anti-viral drug susceptibility test using tagged permissive target cells

The present invention concerns a method of testing the viral susceptibility of a compound. It includes the steps of mixing subject cells infected with a virus with target cells. The target cells of the compound include a marker. Another step includes stimulating viral production. The mixture is then subjected to at least one antiviral compound. Viral production in the target cells is then detected.

Methods of Assigning a COVID Pathological Type and Compositions for Practicing the Same, and Methods of Treating a Subject for Chronic COVID-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Methods of treating a long-hauler subject for chronic COVID-19 by administering a CCR5 or CCL5 antagonist

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Assaying Bladder-Associated Samples, Identifying and Treating Bladder-Associated Neoplasia, and Kits for Use Therein

Methods are provided for assaying bladder-associated samples. Aspects of the methods include detecting per cell programmed-death ligand 1 (PD-L1) expression in a bladder-associated sample. In some instances, the methods include detecting whether an immune cell that expresses PD-Ll above a predetermined threshold is present in a bladder-associated sample and/or detecting a PD-L1-aneuploid-to-PD-L1-epithelial ratio of a bladder-associated sample. Aspects of the methods may also include identifying whether a malignant bladder-associated neoplasia is present. Methods are also provided for treating a subject for a malignant bladder-associated neoplasia, wherein aspects of such methods include administering a therapeutic to a subject having an identified malignant bladder-associated neoplasia. In addition, kits that find use in practicing the subject methods are also provided.

Method of testing adequacy of cells in a specimen

The present invention provides a device and method for determining the adequacy of squamous (ectocervical) cells, columnar (endocervical) cells, neutrophils, and noncellular material in a liquid based cytology specimen. The invention first analyzes a liquid based cytology specimen using light scatter to create a light scatter characteristic representing a predetermined cell. Next the invention determines the presence of squamous (ectocervical) cells versus columnar (endocervical) cells versus neutrophils versus noncellular material using the results of the light scatter. The light scatter characteristic that may be used may be forward light scatter, side light scatter, or both side and forward light scatter.

HPV E6, E7 MRNA assay and methods of use thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Methods of detecting per cell PD-L1 expression and uses thereof

Methods are provided for detecting the per cell programmed-death ligand 1 (PD-L1) expression of neoplasia cells. Aspects of the methods include cytometrically assaying a labeled cell suspension to quantify per cell PD-L1 expression to detect whether a neoplastic cell that expresses PD-L1 above a predetermined threshold is present in the neoplasia sample. In addition, kits that find use in practicing the subject methods are also provided.

HPV E6, E7 MRNA Assay and Methods of Use Thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

LEUKEMIA INHIBITORY FACTOR (LIF) FOR USE IN REPRESSING HUMAN PAPILLOMAVIRUS (HPV) TRANSCRIPTION

Embodiments of the invention are related to leukemia inhibitory factor (LIF) for use in repressing human papillomavirus (HPV) transcription. Processes and related kits are described for treating a HPV-associated papillomatous proliferation, for treating a HPV-associated genital, anal, vulvar, penile, oral, or laryngeal wart, for treating HPV-associated cervical dysplasia or cervical cancer, and for repressing HPV transcription, by administering LIF to a patient in need thereof. A related embodiment is treatment of HPV-16 by use of LIF.

Patterns of known and novel small RNAS in human cervical cancer

Small RNA sequences that are differentially expressed in SCCC cells are provided. The sequences find use in diagnosis of cancer, and classification of cancer cells according to expression profiles. The methods are useful for detecting cervical cancer cells, facilitating diagnosis of cervical cancer and the severity of the cancer (e.g., tumor grade, tumor burden, and the like) in a subject, facilitating a determination of the prognosis of a subject, and assessing the responsiveness of the subject to therapy.

Methods of Treating Cytokine Storm Infections, Including COVID-19, By Inhibiting CCR5/CCL5 (RANTES) Interaction, and Compositions for Practicing the Same

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods of Detecting Per Cell PD-L1 Expression and Uses Thereof

Methods are provided for detecting the per cell programmed-death ligand 1 (PD-L1) expression of neoplasia cells. Aspects of the methods include cytometrically assaying a labeled cell suspension to quantify per cell PD-L1 expression to detect whether a neoplastic cell that expresses PD-L1 above a predetermined threshold is present in the neoplasia sample. In addition, kits that find use in practicing the subject methods are also provided. 1. A method of detecting whether a neoplastic cell that expresses programmed-death ligand 1 (PD-L1) above a predetermined threshold is present in a neoplasia sample , the method comprising:contacting the neoplasia sample with a labeled binding member specific for PD-L1 to generate a labeled cell suspension;cytometrically assaying the labeled cell suspension to quantify per cell PD-L1 expression to detect whether a neoplastic cell that expresses PD-L1 above a predetermined threshold is present in the neoplasia sample.2. The method according to claim 1 , wherein the cytometrically assaying further comprises assaying cell cycle.3. The method according to or claim 1 , wherein the cytometrically assaying further comprises assaying aneuploidy.4. The method according to any of the preceding claims claim 1 , wherein the detected cell is proliferative.5. The method according to any of the preceding claims claim 1 , wherein the labeling further comprises contacting the neoplasia sample with at least one labeled binding member specific for immune cells.6. The method according to any of the preceding claims claim 1 , wherein the detected cell is a circulating tumor cell claim 1 , a hematopoietic cancer cell claim 1 , or a cell of a solid tumor.7. The method according to any of the preceding claims claim 1 , wherein the predetermined threshold is 100 or more PD-L1 molecules per cell.8. A method of identifying whether a neoplasia in a subject is anti-programmed-death ligand 1 (PD-L1) immunotherapy responsive claim 1 , the method comprising: ...

Methods and systems for predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion from a suspension sample of cervical cells

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications.

Methods of evaluating a cellular sample for latent cellular replication competent HIV-1

Methods of evaluating a cellular sample for latent cellular replication competent HIV-1 are provided. Aspects of the methods include contacting a cellular sample with an HIV-1 inducing compound to produce an activated cellular sample; and assessing plasma viral load in the activated cellular sample to evaluate the cellular sample for latent cellular replication competent HIV-1. Also provided are devices and kits that find use in practicing the methods.

HPV E6, E7 MRNA Assay and Methods of Use Thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the In Cell HPV Assay, that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (LBC) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

METHODS AND SYSTEMS FOR PREDICTING WHETHER A SUBJECT HAS A CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) LESION FROM A SUSPENSION SAMPLE OF CERVICAL CELLS

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications.

Process for detecting low abundance RNA in intact cells

The present invention provides a process for detecting the presence of a target mRNA in an intact cell. The process includes the steps of (a) fixing and permeabilizing with a non- or weakly-crosslinking reagent the cell in the presence of a plurality of oligonucleotide probes, wherein each probe (i) contains about 15 to about 30 nucleotides, (ii) is labeled with a detectable marker, (iii) has a matched Tm of greater than about 60° C., and (iv) specifically hybridizes to a different contiguous region of an open reading frame in the target mRNA with the provisos that each probe does not hybridize to itself, does not hybridize to any other probe and does not hybridize to a contiguous sequence of (A)n9 (C)n9 (G)n or (U)n in the target mRNA where n is an integer greater than 5; (b) removing unhybridized probes from the cell; and (c) measuring the detectable label in the cell.

METHODS FOR DETERMINING WHETHER A CERVICAL CELLULAR SAMPLE SHOULD BE TESTED FOR CERVICAL CANCER, AND DEVICES AND KITS FOR PRACTICING THE SAME

Methods for determining whether a cervical cellular sample should be tested for cervical cancer are provided. Aspects of the methods include obtaining cytological data from a cervical cellular sample, and determining whether the cellular sample should be tested for cervical cancer based on the cytological data. Also provided are devices and kits that find use in practicing the methods. The methods, devices and kits find use in a variety of applications, including cervical cancer prescreening.

Methods of Evaluating a Cellular Sample for Latent Cellular Replication Competent HIV-1, and Compositions and Kits for Use in Practicing the Same

Methods of evaluating a cellular sample for latent cellular replication competent HIV-1 are provided. Aspects of the methods include contacting a cellular sample with an HIV-1 inducing compound to produce an activated cellular sample; and assessing plasma viral load in the activated cellular sample to evaluate the cellular sample for latent cellular replication competent HIV-1. Also provided are devices and kits that find use in practicing the methods.

Methods of assaying neoplastic and neoplasia-related cells and uses thereof

Methods are provided for assaying neoplastic cells and/or neoplasia-related cells. Aspects of the methods involve detecting heterogeneity, per cell programmed-death ligand 1 (PD-L1) expression, and/or proliferation of neoplasia and/or neoplasia-related cells. Aspects of the methods include cytometrically assaying a labeled cell suspension to quantify per cell heterogeneity, per cell PD-L1 expression, proliferation, and/or other parameters to detect whether a neoplastic cell is present in the neoplasia sample. Aspects of the provided methods also include treating a subject based on the outcome of such an assay. In addition, kits that find use in practicing the subject methods are also provided.

Method of testing adequacy of cells in a specimen

The present invention provides a device and method for determining the adequacy of squamous (ectocervical) cells, columnar (endocervical) cells, neutrophils, and noncellular material in a liquid based cytology specimen. The invention first analyzes a liquid based cytology specimen using light scatter to create a light scatter characteristic representing a predetermined cell. Next the invention determines the presence of squamous (ectocervical) cells versus columnar (endocervical) cells versus neutrophils versus noncellular material using the results of the light scatter. The light scatter characteristic that may be used may be forward light scatter, side light scatter, or both side and forward light scatter.

Methods for Detecting Cancer-Related Cell Populations, Screening for Metastatic Cancer and Treatments Thereof

Provided are methods involving the assaying of a labeled cell suspension, e.g., to detect cancer-related cells, populations ON thereof and/or screen for metastatic cancer. Labeled cell suspensions may be assayed to detect whether a tumor infiltrating lymphocyte (TIL) population is present in a cellular suspension of a subject. Cancer-related cell populations of interest include, e.g., those expressing one or more markers, including where the markers are members of a marker panel. Markers assayed may vary depending on the context and may include protein markers, nucleic acid markers, cell cycle markers, DNA content markers, and the like. Useful markers include one or more immune checkpoint markers and/or one or more immune cell-type markers, including where the marker(s) assayed are part of one or more panels of markers. Also provided are methods of treating a subject for a neoplasia based on the outcome of an assay of a labeled cell suspension of sample from a subject. Kits for practicing the described methods are also provided. 2. The method according to claim 1 , wherein the plurality of detectable immune cell-type marker binding members comprises specific binding members for two or more immune checkpoint markers selected from the group consisting of: programmed cell death 1 (PD-1) claim 1 , T-cell immunoglobulin mucin receptor 3 (TIM-3) claim 1 , lymphocyte-activation gene-3 (LAG-3) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4).3. The method according to claim 1 , wherein the plurality of detectable immune cell-type marker binding members comprises specific binding members for two or more immune cell-type markers selected from the group consisting of CD3 claim 1 , CD4 claim 1 , CD8 claim 1 , CD16 claim 1 , CD19 claim 1 , CD25 claim 1 , CD56 claim 1 , CD127 and CCR5.4. The method according to claim 1 , wherein the method comprises cytometrically assaying the cellular suspension to determine whether two or more different TIL populations are present in ...

HPV E6, E7 mRNA assay and methods of use thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the "In Cell HPV Assay," that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical ("LBC") cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Methods and Systems for Predicting Whether a Subject Has a Cervical Intraepithelial Neoplasia (CIN) Lesion from a Suspension Sample of Cervical Cells

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications. 170-. (canceled)71. A method of assaying a cell suspension of cervical cells for the presence of a cell of a cervical intraepithelial neoplasia (CIN) lesion , the method comprising:(a) receiving a cell suspension sample of cervical cells; i) cell morphometric data,', 'ii) cell biomarker data, and', 'iii) cell cycle data; and, '(b) flow-cytometrically assaying the received sample for data comprising(c) assessing, from the obtained data, whether a cell of a CIN lesion is present in the sample.72. The method according to claim 71 , wherein the cell biomarker data comprises expression data of one or more HPV gene expression products.73. The method according to claim 72 , wherein the one or more HPV gene expression products comprises an mRNA and the cell biomarker data comprises quantification of the copy number of the mRNA.74. The method according to claim 73 , wherein the copy number of the mRNA is 5 or more.75. The method according to claim 73 , wherein the mRNA comprises E6 mRNA.76. The method according to claim 73 , wherein the mRNA comprises E7 mRNA.77. The method according to claim 71 , wherein the cell morphometric data comprises orthogonal light scatter data claim 71 , forward light scatter data claim 71 , nuclear area data claim 71 , nuclear to cytoplasmic ratio data claim 71 , electronic volume data claim 71 , or a combination thereof.78. The method according to claim 71 , wherein the method further comprises identifying a subpopulation of cells of the sample based on the cell ...

Methods and Systems for Predicting Whether a Subject Has a Cervical Intraepithelial Neoplasia (CIN) Lesion from a Suspension Sample of Cervical Cells

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications. 170-. (canceled)71. A method of detecting the presence of a pre-cancerous cell in a biomarker labeled liquid cellular sample , the method comprising: a) identifying an abnormal cell based on morphometric data, cell cycle data or a combination thereof obtained from cells of the sample; and', 'b) detecting whether the abnormal cell is a pre-cancerous cell based on biomarker quantitation data flow cytometrically obtained from the abnormal cell., 'flow cytometrically assaying an aliquot of the sample, the assaying comprising72. The method according to claim 71 , wherein the abnormal cell is identified based on morphometric data comprising nuclear to cytoplasmic ratio quantitation claim 71 , nuclear area quantitation or a combination thereof.73. The method according to claim 71 , wherein the abnormal cell is identified based on cell cycle data comprising DNA content quantitation.74. The method according to claim 71 , wherein identifying the abnormal cell further comprises electronic volume quantitation.75. The method according to claim 71 , wherein the method further comprises fixing and permeabilizing a liquid cellular sample obtained from a subject to produce a fixed and permeabilized liquid cellular sample used to generate the biomarker labeled liquid cellular sample.76. The method according to claim 75 , wherein the method comprises contacting the fixed and permeabilized liquid cellular sample with a biomarker probe to generate the biomarker labeled liquid cellular sample.77. The method ...

HPV E6, E7 MRNA Assay and Methods of Use Thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology. 155-. (canceled)56. A method of detecting a precancerous cell in a cellular sample obtained from a subject , the method comprising:fixing and permeabilizing the cells of the cellular sample to produce a prepared cellular sample;contacting the cells of the prepared cellular sample with an oligonucleotide probe for a nucleic acid analyte expressed by the precancerous cell;imaging the contacted cells; anddetecting the nucleic acid analyte present in the imaged cells to detect the presence or absence of the precancerous cell in the cellular sample.57. The method according to claim 56 , wherein imaging the cells is performed on a slide.58. The method according to claim 56 , wherein the nucleic acid analyte is an expression product of an oncogene.59. The method according to claim 58 , wherein the oncogene is a viral oncogene.60. The method according to claim 59 , wherein the viral oncogene is an HPV oncogene.61. The method according to claim 60 , wherein the HPV oncogene is HPV E6 or HPV E7.62. The method according to claim 56 , further comprising contacting the cells of the prepared cellular sample with an antibody.63. The method according to claim 56 , further comprising contacting the cells of the prepared cellular sample with a fluorescent nuclear stain.64. ...

HPV E6, E7 MRNA Assay and Methods of Use Thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology. 128-. (canceled)29. A set of reagents comprising:HPV E6, E7 mRNA specific oligonucleotides; anda permeabilization reagent.30. The set of reagents according to claim 29 , further comprising a first pre-hybridization wash fluid.31. The set of reagents according to claim 30 , further comprising a second pre-hybridization wash fluid.32. The set of reagents according to claim 29 , further comprises a hybridization mix.33. The set of reagents according to claim 29 , wherein the HPV specific E6 claim 29 , E7 mRNA oligonucleotides are labeled.34. The set of reagents according to claim 33 , wherein the HPV specific E6 claim 33 , E7 mRNA oligonucleotides are labeled with fluorescein.35. The set of reagents according to claim 34 , wherein the HPV specific E6 claim 34 , E7 mRNA oligonucleotides are 3′ and 5′ labeled with fluorescein.36. The set of reagents according to claim 29 , wherein the permeablization reagent is a fixation reagent.37. The set of reagents according to claim 36 , wherein the set further comprises a first post-hybridization stringency wash.38. The set of reagents according to claim 37 , wherein the set further comprises a second post-hybridization stringency wash.39. The set of reagents according to claim 29 , further comprising a first antibody.40. ...

Methods of Assaying Neoplastic and Neoplasia-Related Cells and Uses Thereof

Methods are provided for assaying neoplastic cells and/or neoplasia-related cells. Aspects of the methods involve de-tecting heterogeneity, per cell programmed-death ligand 1 (PD-L1) expression, and/or proliferation of neoplasia and/or neoplasia-re-lated cells. Aspects of the methods include cytometrically assaying a labeled cell suspension to quantify per cell heterogeneity, per cell PD-L1 expression, proliferation, and/or other parameters to detect whether a neoplastic cell is present in the neoplasia sample. Aspects of the provided methods also include treating a subject based on the outcome of such an assay. In addition, kits that find use in practicing the subject methods are also provided. 1. A method of detecting whether a neoplastic cell having a heterogeneity index above a predetermined threshold is present in a neoplasia sample , the method comprising:contacting the neoplasia sample with a labeled binding member specific for programmed death ligand (PD-L1) to generate a labeled cell suspension;cytometrically assaying the labeled cell suspension to obtain a per cell heterogeneity index comprising quantification of per cell PD-L1 expression to detect whether a neoplastic cell that has a heterogeneity index above a predetermined threshold is present in the neoplasia sample.2. The method according to claim 1 , wherein the heterogeneity index comprises a cytometric measurement of cell complexity.3. The method according to or claim 1 , wherein the heterogeneity index comprises a DNA content determination.4. The method according to any of the preceding claims claim 1 , wherein the detected cell is proliferative.5. The method according to any of the preceding claims claim 1 , wherein the labeling further comprises contacting the neoplasia sample with at least one labeled binding member specific for immune cells.6. The method according to any of the preceding claims claim 1 , wherein the detected cell is a circulating tumor cell claim 1 , a hematopoietic cancer ...

Methods of Assigning a COVID Pathological Type and Compositions for Practicing the Same, and Methods of Treating a Subject for Chronic COVID-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

HPV E6, E7 MRNA Assay and Methods of Use Thereof

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Method of treating COVID-19 by administering the CCR5/CCL5 (RANTES) interaction inhibitor maraviroc

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

HPV E6, E7 mRNA ASSAY AND METHODS OF USE THEREOF

Provided is an HPV E6, E7 mRNA assay, referenced herein as the “In Cell HPV Assay,” that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical (“LBC”) cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Method of inhibition of HIV replication by leukemia inhibitory factor

The present invention concerns a method for inhibiting HIV replication in a cell by binding Leukemia Inhibitory Factors (“LIF”) LIF to its receptor in a cell to inhibit HIV replication within the cell. In addition, the present invention concerns a method for preventing uninfected individuals from infection with HIV by administering a dosage of LIF to prevent establishment of HIV infection. The present invention also provides a method of treating HIV infected individuals by administering a dosage of LIF to prevent disease progression.

Methods and systems for predicting whether a subject has a cervical intraepithelial neoplasia (cin) lesion from a suspension sample of cervical cells

Methods of predicting whether a subject has a cervical intraepithelial neoplasia (CIN) lesion are provided. Aspects of the methods include obtaining both morphometric and biomarker data from a liquid cervical cellular sample and then using both types of data to predict whether the subject has a CIN lesion. Also provided are systems that find use in practicing the methods. The methods and systems find use in a variety of applications, including cervical cancer screening applications.

Method of testing adequacy of specimen cells

Assays for determining malignant transformation of cervical cells by expression of hpv e6, e7 mrna

Provided is an HPV E6, E7 mRNA assay, referenced herein as the "In Cell HPV Assay," that is capable of sensitive and specific detection of normal cervical cells undergoing malignant transformation as well as abnormal cervical cells with pre-malignant or malignant lesions. The In Cell HPV Assay identifies HPV E6, E7 mRNA via in situ hybridization with oligonucleotides specific for HPV E6, E7 mRNA and quantitates the HPV E6, E7 mRNA via flow cytometry. The In Cell HPV Assay can be carried out in less than three hours directly from liquid-based cervical ("LBC") cytology specimens. The In Cell HPV Assay provides an efficient and highly sensitive alternative to the Pap smear for determining abnormal cervical cytology.

Methods of treating a subject for fibromyalgia and compositions for use in the same

Methods of treating a subject for fibromyalgia are provided. Aspects of the methods include administering to the subject a tropane CCR5/CCL5 interaction inhibitor, either alone or in combination with a statin, to treat the subject for fibromyalgia. Also provided are compositions for use in practicing the methods.

Methods and compositions for treating cytokine storm infections, including covid-19, by inhibiting ccr5/ccl5 interaction

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods of treating a subject for post-treatment lyme disease (ptld) and compositions for use in the same

Methods of treating a subject for post-treatment Lyme disease (PTLD) are provided. Aspects of the methods include administering to the subject a tropane CCR5/CCL5 interaction inhibitor in combination with a statin to treat the subject for PTLD. Also provided are compositions for use in practicing the methods.

Methods of treating a subject for myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and compositions for use in the same

Methods of treating a subject for Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are provided. Aspects of the methods include administering to the subject a tropane CCR5/CCL5 interaction inhibitor, either alone or in combination with a statin, to treat the subject for ME/CFS. Also provided are compositions for use in practicing the methods.

Métodos de tratamento de infecções por tempestade de citocina, incluindo covid-19, através da inibição da interação ccr5/ccl5 (rantes) e composições para a prática da mesma

MÉTODOS DE TRATAMENTO DE INFECÇÕES POR TEMPESTADE DE CITOCINA, INCLUINDO COVID-19, ATRAVÉS DA INIBIÇÃO DA INTERAÇÃO CCR5/CCL (RANTES) E COMPOSIÇÕES PARA A PRÁTICA DA MESMA. A presente invenção refere-se a métodos de tratamento de um indivíduo que sofre de COVID-19. Aspectos dos métodos incluindo a administração ao indivíduo de uma quantidade eficaz de um inibidor da interação de CCR5/CCL5, tal como um antagonista de CCR5. Também são fornecidos métodos de avaliação da gravidade de uma doença que envolve a hipercitocinemia, tal como a COVID-19, através da determinação do nível de CCL5/RANTES em um indivíduo, assim como composições para uso em tais métodos.

Methods for determining whether a cervical cellular sample should be tested for cervical cancer, and devices and kits for practicing the same

Methods for determining whether a cervical cellular sample should be tested for cervical cancer are provided. Aspects of the methods include obtaining cytological data from a cervical cellular sample, and determining whether the cellular sample should be tested for cervical cancer based on the cytological data. Also provided are devices and kits that find use in practicing the methods. The methods, devices and kits find use in a variety of applications, including cervical cancer prescreening.

Methods and compositions for treating cytokine storm infections, including covid-19, by inhibiting ccr5/ccl5 interaction

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods and compositions for treating cytokine storm infections, including covid-19, by inhibiting ccr5/ccl5 interaction

Anti-microbial disinfectant and methods of use and production thereof

An acid solution and method of making an acid solution are provided. The method includes exposing a reactant solution to an energy beam to form the acid solution, the reactant solution includes water and a salt. The salt is selected from a group consisting of a chloride salt and a bromide salt and the acid solution is selected from a group consisting of a hypochlorous acid solution and a hypobromous acid solution.

Hiv phenotyping assay, methods, compositions and cells for practicing the same

Human immunodeficiency virus (HIV) phenotyping assays are provided. Such assays may be used in identifying a phenotype of an HIV virion and find use in HIV susceptibility testing as well as other purposes. Methods employing HIV phenotyping assays are also provided including methods that involve the use of target cells contacted with the HIV virion for generating infected cells and/or assessing infection. Also provided are cells that may be contacted with HIV as part of such an assay, methods of infecting cells with HIV, methods of detecting HIV and methods of evaluating a cellular sample for an HIV infection. Methods of treating a subject based on the result of an assay of the present methods, as well as kits and compositions for use in practicing the herein described methods are also provided.

Methods of assigning a covid pathological type and compositions for practicing the same, and methods of treating a subject for chronic covid-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Process for detecting low abundance rna in intact cells

The present invention provides a process for detecting the presence of a target mRNA in an intact cell. The process includes the steps of (a) fixing and permeabilizing with a non-or weakly-crosslinking reagent the cell in the presence of a plurality of oligonucleotide probes, wherein each probe (i) contains about 15 to about 30 nucleotides, (ii) is labeled with a detectable marker, (iii) has a matched Tm of greater than about 60° C, and (iv) specifically hybridizes to a different contiguous region of an open reading frame in the target mRNA with the provisos that each probe does not hybridize to itself, does not hybridize to any other probe and does not hybridize to a contiguous sequence of (A)n9(C)n9(G)n or (U)n in the target mRNA where n is an integer greater than 5; (b) removing unhybridized probes from the cell; and (c) measuring the detectable label in the cell.

Methods of assigning a covid pathological type and compositions for practicing the same, and methods of treating a subject for chronic covid-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Methods of assigning a covid pathological type and compositions for practicing the same, and methods of treating a subject for chronic covid-19

Methods of assigning a COVID pathological type for a subject suffering from COVID-19 are provided. Aspects of the methods include assigning a COVID pathological type for the subject based on a determined quantitative, multiplex cytokine/chemokine panel in a test sample from the subject. Also provided are methods of treating a subject (e.g., a long hauler subject) for chronic COVID-19. Aspects of such methods include administering to the long hauler subject a CCR5/CCL5 interaction inhibitor to treat the long hauler subject. Also provided are compositions for use in practicing the methods. The methods and compositions find use in a variety of applications, including patient stratification, treatment and therapy determination and therapy response assessment.

Process for detecting low abundance rna in intact cells

Process for detecting low abundance rna in intact cells

The present invention provides a process for detecting the presence of a target mRNA in an intact cell. The process includes the steps of (a) fixing and permeabilizing with a non-or weakly-crosslinking reagent the cell in the presence of a plurality of oligonucleotide probes, wherein each probe (i) contains about 15 to about 30 nucleotides, (ii) is labeled with a detectable marker, (iii) has a matched Tm of greater than about 60° C, and (iv) specifically hybridizes to a different contiguous region of an open reading frame in the target mRNA with the provisos that each probe does not hybridize to itself, does not hybridize to any other probe and does not hybridize to a contiguous sequence of (A)n9(C)n9(G)n or (U)n in the target mRNA where n is an integer greater than 5; (b) removing unhybridized probes from the cell; and (c) measuring the detectable label in the cell.

Methods of Assaying Neoplastic and Neoplasia-Related Cells and Uses Thereof

Methods are provided for assaying neoplastic cells and/or neoplasia-related cells. Aspects of the methods involve detecting heterogeneity, per cell programmed-death ligand 1 (PD-L1) expression, and/or proliferation of neoplasia and/or neoplasia-related cells. Aspects of the methods include cytometrically assaying a labeled cell suspension to quantify per cell heterogeneity, per cell PD-L1 expression, proliferation, and/or other parameters to detect whether a neoplastic cell is present in the neoplasia sample. Aspects of the provided methods also include treating a subject based on the outcome of such an assay. In addition, kits that find use in practicing the subject methods are also provided.

Hpv-e6-, -e7-mrna-test und verwendungsverfahren dafür

Methods for detecting cancer-related cell populations, screening for metastatic cancer and treatments thereof

Provided are methods involving the assaying of a labeled cell suspension, e.g., to detect cancer-related cells, populations thereof and/or screen for metastatic cancer. Labeled cell suspensions may be assayed to detect whether a tumor infiltrating lymphocyte (TIL) population is present in a cellular suspension of a subject. Cancer-related cell populations of interest include, e.g., those expressing one or more markers, including where the markers are members of a marker panel. Markers assayed may vary depending on the context and may include protein markers, nucleic acid markers, cell cycle markers, DNA content markers, and the like. Useful markers include one or more immune checkpoint markers and/or one or more immune cell-type markers, including where the marker(s) assayed are part of one or more panels of markers. Also provided are methods of treating a subject for a neoplasia based on the outcome of an assay of a labeled cell suspension of sample from a subject. Kits for practicing the described methods are also provided.