Abstract: This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: Adjustable-prescription orthodontic bracket assemblies. The orthodontic bracket assemblies include a bracket body, an arcuate core, and a retention structure. The bracket body defines an arcuate receptacle that extends toward a base of the bracket body from a top of the bracket body. The arcuate core is received within the arcuate receptacle and defines an archwire slot. The arcuate receptacle is shaped to retain the arcuate core therein and to permit rotation of the arcuate core therein. The retention structure is configured to selectively retain the arcuate core at a selected rotational orientation with the bracket body. The retention structure is configured to selectively transition between a disengaged configuration, in which the retention structure permits rotation of the arcuate core relative to the bracket body, and an engaged configuration, in which the retention structure retains the arcuate core at the selected rotational orientation.

Abstract: This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, other AR-expressing cancers, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels (through degradation) and/or activity (through inhibition) of any androgen receptor including androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: Adjustable-prescription orthodontic bracket assemblies are disclosed herein. The orthodontic bracket assemblies include a bracket body, an arcuate core, and a retention structure. The bracket body defines an arcuate receptacle that extends toward a base of the bracket body from a top of the bracket body. The arcuate core is received within the arcuate receptacle and defines an archwire slot. The arcuate receptacle is shaped to retain the arcuate core therein and to permit rotation of the arcuate core therein. The retention structure is configured to selectively retain the arcuate core at a selected rotational orientation with the bracket body. The retention structure is configured to selectively transition between a disengaged configuration, in which the retention structure permits rotation of the arcuate core relative to the bracket body, and an engaged configuration, in which the retention structure retains the arcuate core at the selected rotational orientation.

Abstract: This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and/or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and/or gynecomastia.

Abstract: This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, other AR-expressing cancers, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels (through degradation) and/or activity (through inhibition) of any androgen receptor including androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Abstract: Systems and methods for communicating orthodontic treatment information are disclosed herein. The methods may include methods of delivering an informational resource corresponding to an orthodontic treatment instruction to a patient of an orthodontist, and optionally to a caretaker of the patient and a dentist of the patient. The methods may further include delivering receipt information to the orthodontist and/or the caretaker, wherein the receipt information is indicative of an interaction between the patient and the informational resource. The systems may include electronic devices and interfaces associated with the orthodontist, the patient, the caretaker, and the dentist that may facilitate the communication methods.

Abstract: Orthodontic appliance systems including self-ligating orthodontic brackets and/or orthodontic brackets that include a prescription-altering insert that is configured to be removably coupled to the bracket. The prescriptive insert may be optional in some embodiments. In some embodiments, the prescriptive insert may define and/or alter the prescription of the bracket, such as a prescription defined by the bracket when the insert is not utilized. A plurality of prescriptive inserts may be provided, with each insert defining a unique orthodontic prescription when coupled to the bracket. In some embodiments, the bracket is a self-ligating bracket that includes a base and a repositionable closure for selectively obstructing an opening in an archwire passage of the bracket. In some embodiments, the closure defines more than one side, or wall, of the archwire passage and/or is pivotally coupled to the base by a floating hinge or other displaceable positioning mechanism.

Abstract: Devices, systems, and methods for adjusting a prescription of a plurality of orthodontic brackets are disclosed herein. The devices include an orthodontic prescription-defining device that includes a plurality of contacting structures and a plurality of prescription-defining engagement structures. The systems include the orthodontic prescription-defining device and a plurality of orthodontic brackets. The methods include unlocking each of a plurality of orthodontic brackets, operatively contacting a plurality of contacting structures of an orthodontic prescription-defining device with a plurality of intra-oral reference points, urging each of a plurality of archwire slots to a respective preselected orientation, and locking each of the plurality of orthodontic brackets in the preselected orientation.

Abstract: Electromechanical systems, methods, orthodontic brackets, and tools for adjusting orthodontic prescriptions of orthodontic brackets with adjustable archwire passages are disclosed herein. The methods include operatively engaging an orthodontic bracket with an engagement structure of an electronic orthodontic adjustment tool, electronically determining a present orientation of an archwire slot of the orthodontic bracket, displaying a displayed orientation of the archwire slot, and adjusting the orientation of the archwire slot based on the displayed orientation. The orthodontic brackets include a base, a body, a retention structure, an orientation-determining structure, and a transmitter. The tools include an engagement structure, an orientation-determining structure, and an orientation indicator.

Abstract: Adjustable-prescription orthodontic bracket assemblies are disclosed herein. The orthodontic bracket assemblies include a bracket body, an arcuate core, and a retention structure. The bracket body defines an arcuate receptacle that extends toward a base of the bracket body from a top of the bracket body. The arcuate core is received within the arcuate receptacle and defines an archwire slot. The arcuate receptacle is shaped to retain the arcuate core therein and to permit rotation of the arcuate core therein. The retention structure is configured to selectively retain the arcuate core at a selected rotational orientation with the bracket body. The retention structure is configured to selectively transition between a disengaged configuration, in which the retention structure permits rotation of the arcuate core relative to the bracket body, and an engaged configuration, in which the retention structure retains the arcuate core at the selected rotational orientation.

Abstract: Mechanically bistable thermal devices and methods of utilizing the same. The mechanically bistable thermal devices include a mechanically bistable element and a thermal element. The mechanically bistable element is configured to be selectively transitioned between a straight conformation, in which the mechanically bistable element defines an elongate shape, and a wrapped conformation, in which the mechanically bistable element defines an arcuate shape and is configured to at least partially encircle an encircled form. The thermal element is configured to exchange thermal energy with the encircled form when in thermal contact with the encircled form and includes a thermal material that includes a fluid and/or a granular solid. The methods include activating the thermal element and transitioning the mechanically bistable element from the straight conformation to the wrapped conformation to at least partially encircle the encircled form with the mechanically bistable device.

Abstract: The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and/or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and/or gynecomastia.

Abstract: Orthodontic bracket assemblies with torque-adjusting drums. The drum defines at least a majority of the archwire slot of the corresponding bracket assembly, and the drum may be selectively rotated about its longitudinal axis to adjust the prescriptive force that is applied to a patient's tooth during orthodontic use of the bracket assembly. The bracket assembly includes a positioning assembly that selectively retains the drum in a selected orientation relative to the base of the bracket assembly, thereby defining a prescription to be imparted by the bracket assembly to a patient's tooth. In some embodiments, the bracket assembly includes a biasing mechanism that selectively urges the positioning assembly to a position in which the drum is, or is not, retained in a selected position. In some embodiments, the bracket includes a release mechanism that selectively disengages the positioning assembly to permit adjustment of the drum.

Abstract: The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and/or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and/or gynecomastia.

Abstract: The present invention relates to methods for reducing testosterone levels by reduction of luteinizing hormone (LH) or independent of LH levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC) and palliative treatment of prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and/or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels.