Abstract: The present disclosure generally relates to compositions and methods for predicting or diagnosing immune-related adverse events (irAE) before, during, or after immune checkpoint inhibitor (ICI) treatment in a subject with cancer. The method includes assessment of transcripts, autoantibody levels, cytokine levels, and immune cells. The irAE can be ICI-related myositis, ICI-related myocarditis or ICI-related myositis and myocarditis.

Abstract: A method to reinforce a built structure, wherein an impregnation resin including a resin component including at least one epoxy resin and hardener component including at least one amine of the formula (I) is used to impregnate woven or stitched fabric, which is wrapped around and/or adhered onto built structure. The inventive method preferably serves to improve earthquake safety of buildings, as replacement for missing reinforcement inside concrete, for improvement of strength and ductility or for increase of payload of a built structure. It enables the application of an emission-free impregnation resin with low odour, which has a long open time and good penetration into the fabric, shows fast and reliable curing without tendency to blushing, and forms a dry, non-sticky surface. The cured impregnation resin has a high strength, a high glass transition temperature and good adhesion properties, enabling a good durability and long-term stability of the reinforced structure.

Abstract: A computer system to implement automated parametric modeling of a built environment and simulating applying a plurality of sustainability metrics to respective modeled built environments.

Abstract: The invention relates to therapeutic compositions for disorders associated with haploinsufficiency. The invention provides antisense oligonucleotides useful for treating neurodevelopmental disorders associated with mutations in the SYNGAP gene. The invention provides compositions that include synthetic antisense oligonucleotides (ASOs) that promote expression of the SynGAP protein by one or any combination of (i) preventing one or more miRNAs from interfering with production of the SynGAP protein; (ii) binding to the 5?-UTR of the SYNGAP1 transcript and augmenting translation of the Syngap protein; and (iii) promoting RNAseH cleavage of antisense long non-coding RNAs that are anticorrelated with SYNGAP expression. When the composition is delivered to a patient with SYNGAP haploinsufficiency, the ASOs promote expression of the SynGAP protein.

Abstract: Disclosed herein is a guide device and a driver, which allows for the preparation of an anatomic cavity for screw fixation of an implant or spacer, including the guidance for hole preparation, and guidance for insertion of screws, and or anchors, while selecting the amount of rigidity, and selecting the amount of visibility.

Abstract: The invention relates to therapeutic compositions for disorders associated with haploinsufficiency. The invention provides antisense oligonucleotides useful for treating early-onset epileptic encephalopathy by promoting expression of Syntaxin-binding protein 1 (STXBP1). The invention provides compositions that include synthetic antisense oligonucleotides (ASOs) that prevent certain miRNAs from interfering with production of the STXBP1 protein or bind to the 5?-UTR of the STXBP1 transcript and augment translation of the STXBP1 protein. When the composition is delivered to a patient with STXBP1 haploinsufficiency, the ASOs prevent miRNA from downregulating synthesis of STXBP1 protein.

Abstract: An intervertebral implant component of an intervertebral implant includes an outer surface for engaging an adjacent vertebra and an inner surface. A keel extends from the outer surface and is designed to be disposed in a slot provided in the adjacent vertebra. This keel extends in a plane which is non-perpendicular to the outer surface; and preferably there are two of the keels extending from the outer surface which are preferably offset laterally from one another. In another embodiment, an anterior shelf is provided at an anterior end of the outer surface, and this anterior shelf extends vertically away from the inner surface in order to help prevent bone growth from the adjacent vertebra towards the inner surface. Further in accordance with disclosed embodiments, various materials, shapes and forms of construction of the component and/or keel provide various benefits.

Abstract: Disclosed herein is a guide device and a driver, which allows for the preparation of an anatomic cavity for screw fixation of an implant or spacer, including the guidance for hole preparation, and guidance for insertion of screws, and or anchors, while selecting the amount of rigidity, and selecting the amount of visibility.

Abstract: A method of making an implantable device includes directing a projection of laser energy having a plurality of adjacent energy pixels on a build surface atop a bed of powder, thereby forming a layer of the implantable device. The directing step is repeated a plurality of times, in a layer-by-layer manner, such that a totality of the formed layers define at least a portion of the implantable device.

Abstract: The invention provides systems and methods for discovering candidate therapies for genetic conditions and also for screening those therapies in vitro for evidence of neurotoxicity. Where a medical condition is a consequence of a genetic target such as a mutated gene, the disclosure provides in silico methods to generate lists of candidate sequences for antisense oligonucleotides (ASOs) that will potentially bind to the gene or transcripts from the gene in vivo and treat the associated condition by restoring a healthy phenotype of gene expression. The invention provides in vitro methods for screening candidate ASO sequences for symptoms of neurotoxicity in vivo. For example, candidate sequences that are output by the in silico analytical pipeline can be synthesized and assayed against live cells in vitro.

Abstract: The invention provides therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a Nav channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating Nav channel synthesis, which inhibits the neuron's ability to contribute to certain conditions such as epilepsy and pain perception. The ASO binds to one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings.

Abstract: The invention provides compositions useful to knock down overexpression of UBE3A and treat conditions associated with Dup15q syndrome. The compositions include antisense oligonucleotides, preferably short oligonucleotides that are complementary to, and hybridize to, UBE3A transcripts in vivo. The ASOs prevent or inhibit successful translation of UBE3A mRNA into protein. Specifically, preferred embodiments include anti-UBE3A gapmers—oligos that include a central DNA portion flanked by RNA wings. When the gapmer hybridizes to UBE3A pre-mRNA or mRNA, the duplex hybrid recruits RNaseH, which cleaves, or digests, the UBE3A pre-mRNA or mRNA, preventing expression of the UBE3A protein. Because the ASOs prevent expression of the UBE3A protein, treatment with a composition including ASOs of the disclosure may be effective to knock down overexpression of UBE3A.

Abstract: The invention provides non-opioid pain therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a NaV channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating NaV channel synthesis, which inhibits the neuron's ability to contribute to the perception of pain. The ASO targets one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings. When the composition is delivered to dorsal root ganglion (DRG) neurons in vitro, the DRG neurons exhibit a dose-dependent knockdown of NaV1.7, NaV1.8, or NaV1.9.

Abstract: An intervertebral implant component of an intervertebral implant includes an outer surface for engaging an adjacent vertebra and an inner surface. A keel extends from the outer surface and is designed to be disposed in a slot provided in the adjacent vertebra. This keel extends in a plane which is non-perpendicular to the outer surface; and preferably there are two of the keels extending from the outer surface which are preferably offset laterally from one another. In another embodiment, an anterior shelf is provided at an anterior end of the outer surface, and this anterior shelf extends vertically away from the inner surface in order to help prevent bone growth from the adjacent vertebra towards the inner surface. Further in accordance with disclosed embodiments, various materials, shapes and forms of construction of the component and/or keel provide various benefits.

Abstract: Disclosed herein is a guide device and a driver, which allows for the preparation of an anatomic cavity for screw fixation of an implant or spacer, including the guidance for hole preparation, and guidance for insertion of screws, and or anchors, while selecting the amount of rigidity, and selecting the amount of visibility.

Abstract: An intervertebral implant component of an intervertebral implant includes an outer surface for engaging an adjacent vertebra and an inner surface. A keel extends from the outer surface and is designed to be disposed in a slot provided in the adjacent vertebra. This keel extends in a plane which is non-perpendicular to the outer surface; and preferably there are two of the keels extending from the outer surface which are preferably offset laterally from one another. In another embodiment, an anterior shelf is provided at an anterior end of the outer surface, and this anterior shelf extends vertically away from the inner surface in order to help prevent bone growth from the adjacent vertebra towards the inner surface. Further in accordance with disclosed embodiments, various materials, shapes and forms of construction of the component and/or keel provide various benefits.

Abstract: Disclosed herein is a guide device and a driver, which allows for the preparation of an anatomic cavity for screw fixation of an implant or spacer, including the guidance for hole preparation, and guidance for insertion of screws, and or anchors, while selecting the amount of rigidity, and selecting the amount of visibility.

Abstract: An intervertebral implant component of an intervertebral implant includes an outer surface for engaging an adjacent vertebra and an inner surface. A keel extends from the outer surface and is designed to be disposed in a slot provided in the adjacent vertebra. This keel extends in a plane which is non-perpendicular to the outer surface; and preferably there are two of the keels extending from the outer surface which are preferably offset laterally from one another. In another embodiment, an anterior shelf is provided at an anterior end of the outer surface, and this anterior shelf extends vertically away from the inner surface in order to help prevent bone growth from the adjacent vertebra towards the inner surface. Further in accordance with disclosed embodiments, various materials, shapes and forms of construction of the component and/or keel provide various benefits.

Abstract: A method for implantation of an intervertebral implant for fusing vertebrae is disclosed. The implant may comprise a body constructed of a radiolucent material and having a thickness between a superior and an inferior face greatest at a middle portion of the body and tapered toward each end, and two vertical through-channels extending through the body from the superior to the inferior face, the channels being spaced from one another in a way to define a wall extending between the channels from the superior to the inferior face; and at least three radiopaque markers extending substantially through the body from the superior to the inferior face and disposed in the body so as to be enclosed in the radiolucent material of the body from the superior to the inferior face to indicate implant location and size in postoperative spinal scans.

Abstract: An instrument system, associated milling or drilling guide and method include use of a trial implant of a size corresponding to an actual implant for the intervertebral space, with a milling guide mounted on the trial implant. The system also includes a cutting tool which is used to form a cutout in an adjacent vertebra.