Abstract: Needle shield removers, drug delivery devices, and associated methods are provided that include a tubular body formed from a sheet with a closure having from a plurality of teeth extending laterally outwardly from one longitudinal edge of the sheet and a plurality of grooves extending laterally inwardly into the sheet of material from a second longitudinal edge of the sheet. The plurality of teeth are frictionally received within the plurality of grooves to thereby hold the body in a tubular configuration. The needle shield removers can further include a first plurality of barbs arrayed around a circumference of the body adjacent to a first end thereof and a second plurality of barbs arrayed around a circumference of the body adjacent to a second end thereof.

Abstract: A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.

Abstract: A method of manufacturing a plunger of a drug delivery device includes forming a plunger body. The method includes loading the plunger body into a cavity of a first molding tool of a molding system. The cavity is at least partially defined by a first molding portion and a second molding portion. The method includes coupling a second molding tool to the first molding tool to form a plurality of channels defined by grooves in the first and second molding tools, and injecting molten plastic into the plurality of channels to form an overmolded plunger body. The overmolded plunger body includes a head coupled to the first end of the plunger body and a foot coupled to the second end of the plunger body. The foot is at least partially coupled to the inner wall and the head is coupled to the outer wall of the plunger body.

Abstract: A method of manufacturing a plunger of a drug delivery device includes forming a plunger body. The method includes loading the plunger body into a cavity of a first molding tool of a molding system. The cavity is at least partially defined by a first molding portion and a second molding portion. The method includes coupling a second molding tool to the first molding tool to form a plurality of channels defined by grooves in the first and second molding tools, and injecting molten plastic into the plurality of channels to form an overmolded plunger body. The overmolded plunger body includes a head coupled to the first end of the plunger body and a foot coupled to the second end of the plunger body. The foot is at least partially coupled to the inner wall and the head is coupled to the outer wall of the plunger body.

Abstract: Provided herein are compositions, systems, kits, and methods for generating human podocyte cells by contacting human nephron progenitor cells with an FGFR pathway inhibitor, a BMP pathway inhibitor, and a WNT pathway inhibitor. In certain embodiments, the nephron progenitor cells are further contacted with at least one factor selected from: BMP4, BMP7, lysophosphatidic acid, and gamma-secretase inhibitor XX. In certain embodiments, the contacting the nephron progenitor cells is performed under serum-free conditions.

Abstract: Provided herein are compositions, systems, kits, and methods for generating human podocyte cells by contacting human nephron progenitor cells with an FGFR pathway inhibitor, a BMP pathway inhibitor, and a WNT pathway inhibitor. In certain embodiments, the nephron progenitor cells are further contacted with at least one factor selected from: BMP4, BMP7, lysophosphatidic acid, and gamma-secretase inhibitor XX. In certain embodiments, the contacting the nephron progenitor cells is performed under serum-free conditions.

Abstract: A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.

Abstract: A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.

Abstract: The present invention relates to combination therapies for treating viral infections, particularly infections by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2, also known as coronavirus disease 2019 (COVID-19).

Abstract: A method of manufacturing a plunger of a drug delivery device includes forming a plunger body. The method includes loading the plunger body into a cavity of a first molding tool of a molding system. The cavity is at least partially defined by a first molding portion and a second molding portion. The method includes coupling a second molding tool to the first molding tool to form a plurality of channels defined by grooves in the first and second molding tools, and injecting molten plastic into the plurality of channels to form an overmolded plunger body. The overmolded plunger body includes a head coupled to the first end of the plunger body and a foot coupled to the second end of the plunger body. The foot is at least partially coupled to the inner wall and the head is coupled to the outer wall of the plunger body.

Abstract: Provided herein are compositions, systems, kits, and methods for generating dorsal foregut endoderm (DFE) cells by contacting pluripotent stem cells with a retinoic acid signaling pathway agonist and a bone morphogenetic (BMP) pathway inhibitor without exposing the stem cells to a transforming growth factor beta (TGF?) pathway agonist. In certain embodiments, the DFE cells are contacted with a retinoic acid signaling pathway agonist and a FGFR pathway inhibitor to generate pancreatic endoderm (PE) cells (e.g., with dorsal identity). In other embodiments, the PE cells are contacted with an ALK5 inhibitor and a Notch inhibitor to generate endocrine cells (e.g., insulin expressing endocrine cells). In certain embodiments, compositions, systems, kits, and methods are provided for generating anterior domain endoderm (ADE) cells.

Abstract: Needle shield removers, drug delivery devices, and associated methods are provided that include a tubular body formed from a sheet with a closure having from a plurality of teeth extending laterally outwardly from one longitudinal edge of the sheet and a plurality of grooves extending laterally inwardly into the sheet of material from a second longitudinal edge of the sheet. The plurality of teeth are frictionally received within the plurality of grooves to thereby hold the body in a tubular configuration. The needle shield removers can further include a first plurality of barbs arrayed around a circumference of the body adjacent to a first end thereof and a second plurality of barbs arrayed around a circumference of the body adjacent to a second end thereof.

Abstract: A drug delivery device may include a housing defining a longitudinal axis and having an opening and a drug storage container including a delivery member having an insertion end configured to extend at least partially through the opening during a delivery state. The device may also include plunger moveable toward the distal end of the drug storage container to expel a drug from the drug storage container through the delivery member, the plunger including a body portion having an inner wall defining an axial chamber and an outer wall cooperating with the inner wall to define a body thickness. The device may further include a plunger biasing member disposed at least partially within the axial chamber, the plunger biasing member configured to urge the plunger toward the distal end of the drug storage container.

Abstract: Provided herein are compositions, systems, kits, and methods for generating human podocyte cells by contacting human nephron progenitor cells with an FGFR pathway inhibitor, a BMP pathway inhibitor, and a WNT pathway inhibitor. In certain embodiments, the nephron progenitor cells are further contacted with at least one factor selected from: BMP4, BMP7, lysophosphatidic acid, and gamma-secretase inhibitor XX. In certain embodiments, the contacting the nephron progenitor cells is performed under serum-free conditions.

Abstract: The invention is based, in part, on the discovery that a polypeptide, referred to herein as Betacam, is selectively expressed on the surface of pancreatic islet cells. Thus, in one aspect, the invention is directed to compositions comprising Betacam or that can be used to detect Betacam. In another aspect, the invention provides methods of detecting (e.g., non-invasively) pancreatic beta cells from a mammalian cell source. Another aspect of the invention is directed to cellular purification of pancreatic beta cells from a heterogeneous cell source of multiple kinds. In another aspect, the invention provides methods of identifying agents that modulate activity of Betacam. In yet another aspect, the invention provides for improved treatment and diagnosis of diabetes.

Abstract: The present solution relates to an improved system and method for providing interactive content. The present solution can provide a first content object for display in a content slot of an information resource of a content provider. The first content object can include one or more tags that can each be linked to a respective second content object of a plurality of second content object. When an interaction is received with a first tag the system can identify a second content object corresponding to the first tag. The second content object can be provided for display in the same content slot of the information resource. In some implementations, the second content object can include a transaction interface to purchase an item identified in the second content object.

Abstract: The invention is based, in part, on the discovery that a polypeptide, referred to herein as Betacam, is selectively expressed on the surface of pancreatic islet cells. Thus, in one aspect, the invention is directed to compositions comprising Betacam or that can be used to detect Betacam. In another aspect, the invention provides methods of detecting (e.g., non-invasively) pancreatic beta cells from a mammalian cell source. Another aspect of the invention is directed to cellular purification of pancreatic beta cells from a heterogeneous cell source of multiple kinds. In another aspect, the invention provides methods of identifying agents that modulate activity of Betacam. In yet another aspect, the invention provides for improved treatment and diagnosis of diabetes.

Abstract: The present solution relates to an improved system and method for providing interactive content. The present solution can provide a first content object for display in a content slot of an information resource of a content provider. The first content object can include one or more tags that can each be linked to a respective second content object of a plurality of second content object. When an interaction is received with a first tag the system can identify a second content object corresponding to the first tag. The second content object can be provided for display in the same content slot of the information resource. In some implementations, the second content object can include a transaction interface to purchase an item identified in the second content object.

Abstract: A method of inducing pancreatic fates from human multipotent or pluripotent cells includes obtaining a cell population comprising human multipotent or pluripotent cells and providing the cell population with at least three of (i) an CXCR4 agonist, (ii) an EGFR agonist, (iii) an FGFR agonist, (iv) an Activin receptor agonist or an agent that stimulates SMAD3, (v) an IL11R agonist or IL6R agonist, (vi) a notch agonist, (vii) an RXR agonist or RAR agonist, or (viii) a BMP inhibitor for a time effective to allow the differentiation of pancreatic precursor cells from the human multipotent or pluripotent cells.

Abstract: Described is the identification of ZnT8 as an autoantigen target in type I autoimmune diabetes (T1D), other autoimmune disease, and other diabetes-linked diseases and conditions. Also described are a variety of therapeutic, diagnostic, and prognostic tools and methods based on this discovery. The identification of genetic variation in ZnT8 as an important player in the initiation of the disease process and the progression of autoimmunity to clinical diabetes is disclosed.