Abstract: Provided herein are methods and compositions related to treating motor neuron diseases, such as ALS, in a subject by administering to the subject (e.g., orally administering to the subject) a composition comprising nicotinamide riboside, pterostilbene and a phosphodiesterase (PDE) inhibitor, including a PDE4 inhibitor such as ibudilast, and also including a thiol/cysteine donor, such as acetylcysteine.

Abstract: Disclosed herein are programmable bacteria for tumor-targeted immunotherapeutic delivery. In certain embodiments, the programmable bacteria comprise at least one synchronized lysis circuit contained in a single operon which are capable of being further engineered to cyclically produce anti-cancer therapeutic agents including but not limited to nanobodies against immune checkpoint inhibitors and over-expressed markers in cancers, toxins, tumor antigens, cytokines, and chemokines. In some embodiments, the programmable bacteria comprise at least one synchronized lysis circuit contained in a single operon and at least one plasmid producing a therapeutic agent, i.e., at least one plasmid comprising a nucleic acid sequence which encodes a therapeutic agent. The disclosure also provides methods of curing and treating cancer using the programmable bacteria.

Abstract: The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

Abstract: Disclosed herein are methods and kits for identifying a subject as having colon cancer. Also provided herein are methods and kits for determining the prognosis of a subject having colon cancer and for determining the progression of colon cancer in a subject.

Abstract: A depleted sequencing library can be prepared by providing a composition comprising a heterogeneous mixture of linear nucleic acids having a first terminus and a second terminus. A first subset of target nucleic acids and a second subset of non-target nucleic acids can include a first adaptor region at the first terminus and a second adaptor region at the second terminus. A third subset of the target nucleic acids and a fourth subset of the non-target nucleic acids include the second adaptor region at the first terminus and at the second terminus. Removable blocker oligonucleotides can be added to the composition, non-target nucleic acids can be removed from the composition by sequence capture to bait oligonucleotides, and the composition can be treated to reduce a quantity of free blocker oligonucleotides that are not annealed to an adaptor sequence or to a sequence substantially complementary to an adaptor sequence.

Abstract: The present invention relates to a composition for surface modification. The composition for surface modification according to the present invention contains a particular carbodiimide-based compound, thus forms a covalent bond without damaging skin, hair, or fabric, and semipermanently provides desired skin or hair surface modification effects or fabric care effects.

Abstract: An optical-based oscillometric blood pressure measurement device includes a cuff, which is pneumatically connected to an inflation/deflation unit and electronically connected to a pressure detection unit. It also includes light emission diode and photodiode pairs, and a volume detection unit that converts the plethysmogram received by the photodiode to the optical oscilloetrygram as the artery volume signal. Its control unit determines inflation/deflation slopes and the start/stop pressures and accurately traces the prescribed controller set point. Its extraction unit measures the systolic, diastolic, and mean arterial pressure accurately.

Abstract: A multi-ply tissue paper product includes at least three plies. The tissue paper product includes a first inner ply being a creped ribbed ply and having a basis weight of 10 to 30 gsm, and a first outermost ply and a second outermost ply on each side of said inner ply, the first and second outermost plies being non-ribbed plies, wherein a creped ribbed ply is a ply including ribs and valleys providing an average core roughness Rk in the range 10 to 300 ?m, and peaks being 4 to 12 per cm as measured along said first direction; and wherein a non-ribbed ply is a ply displaying no parallel ribs and valleys extending continuously along any direction of the ply or displaying parallel ribs and valleys extending continuously along any direction of the ply, the ribs and valleys providing peaks being less than 4 per cm.

Abstract: A working electrode for a subcutaneous sensor for use with a continuous biological monitor for a patient is disclosed. The working electrode includes a conductive substrate and an enzyme layer on the conductive substrate. The enzyme layer includes an enzyme, and the enzyme selected according to a biological function to be monitored. A hydrophobic material cross-linked with an acrylic polyol is included. The enzyme is fully entrapped in the cross-linked hydrophobic material with the acrylic polyol.

Abstract: In various aspects, methods and formulations are provided for treating subjects, in particular mammals, intranasally with an effective amount of insulin, an insulin analog, or an insulin derivative to treat or prevent an eye disease, in particular a diabetic eye disease such as diabetic retinopathy.

Abstract: The present disclosure provides a pharmaceutical composition that includes enclomiphene and pregnenolone, and pharmaceutical combinations and uses thereof. The present disclosure also provides a pharmaceutical combination that includes a selective estrogen receptor modulator and testosterone in a form suitable for oral administration, and uses thereof.

Abstract: A device for treating Dupuytren's contracture in a hand of a patient includes a handle, a shaft extending from the handle and sized to fit through a small incision on the hand and under a target tissue, a sharp distal tip on the shaft, a retrograde blade on the shaft, facing proximally toward the handle, and an opening in the shaft, adjacent the retrograde blade. In alternative embodiments, the retrograde blade faces either upward or downward relative to the shaft. Optionally, the treatment device may include a blade protector slidably disposed along the shaft from the handle to the retrograde blade and a slider on the handle, connected to the blade protector, to slide the blade protector along the shaft from a blade protecting position to a blade exposed position.

Abstract: An outlet assembly for arrangement to an outer wall of a dispenser for web-shaped absorbent material, the outlet assembly comprises a first part defining a first outlet portion and a second part defining a second outlet portion wherein the first part comprises a rim attachment element such that the first part assumes a first part fixed position in relation to the wall opening outer rim, the first part further comprises a first connector element, and the second part comprises a second connector element, the first connector element and the second connector element being such that the second part can be attached to the first part by means of connection between the first connector element and the second connector element such that the second part assumes a second part fixed position in relation to the first part.

Abstract: Composition for use in a method of improving the human male's semen quality, said composition comprising at least one source of spermidine, and optionally one or more further components and/or one or more carriers or excipients.

Abstract: The present invention generally relates to systems and methods for delivering and/or receiving a substance or substances such as blood, from subjects, e.g., from the skin and/or from beneath the skin. In one aspect, the present invention is generally directed to devices and methods for receiving or extracting blood from a subject, e.g., from the skin and/or from beneath the skin, using devices containing a fluid transporter (for example, one or more microneedles), and a storage chamber having an internal pressure less than atmospheric pressure prior to receiving blood. In some cases, the device may be self-contained, and in certain instances, the device can be applied to the skin, and activated to receive blood from the subject. The device, or a portion thereof, may then be processed to determine the blood and/or an analyte within the blood, alone or with an external apparatus.

Abstract: The present invention relates to a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells, for use in a method for the treatment of an inflammatory disease. The invention also relates to a method for treating an inflammatory disease by administering a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells. In addition, the invention relates to a method for identifying a subject likely to be resistant to steroid treatment, as well as a subject likely to benefit from treatment with a calcineurin inhibitor.

Abstract: Systems, methods and interfaces are provided for processing natural language queries. A machine learning-powered search interface may process complex natural language queries across specialized domains. The method may utilize a transformer-based natural language processing model that analyzes user intent by examining both current and historical user inputs. A graph data structure may be used to represent interconnected domains like patient records, insurance claims, and business metrics enables dynamic information retrieval. The system may use an A* search algorithm to navigate domain nodes and identify relevant answers. An abbreviation expansion mechanism resolves technical shorthand by referencing domain-specific mapping databases, ensuring precise interpretation of user queries. The method may identify keywords, traces optimal answer pathways, and adapt by updating graph relationships and abbreviation mappings.

Abstract: An absorbent core having a length in a longitudinal direction and a width in a transverse direction, including upper and lower core cover layers and absorbent material sandwiched therebetween, and a pair of channels extending in the longitudinal direction in the absorbent material, each of the channels being free or substantially free from absorbent material and having a channel seal extending therein and joining the core cover layers. For at least one transversal segment of the absorbent core including the channel seals, one core cover layer has a first width between the channel seals, and the other core cover layer has a second width between the channel seals, wherein the first and second widths of the core cover layers are the widths of the core cover layers between the channel seals in an unfolded, flat-out state and wherein the first width is no less than 120% of the second width.