anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Novel compounds of the general formula <FORM:1076069/C2/1> in which Ph represents an optionally substituted orthophenylene radical, Ph1 an optionally substituted phenyl radical, R1 a hydrocarbon radical of aliphatic character, and R2 a hydrogen atom or a C1- 7 alkyl radical, and acid addition salts thereof; are prepared either by reaction of a compound of the formula R1X in which R1 has the meaning given above and X represents a halogen atom with a tetrahydrobenzoxazepine of the formula <FORM:1076069/C2/2> or by reductive alkylation, or by reduction of the corresponding 4-acyl compound with lithium aluminium hydride.  In the products, alkenyl groups can, for example, be reduced to alkyl groups, and racemic products can be resolved.  The novel tetrahydrobenzoxazepines of the second general formula above are prepared by reduction of corresponding 3,5-dioxo compounds with lithium aluminium hydride.  The novel 4-acyl compounds of the general formula <FORM:1076069/C2/3> in which R11CH2-has the same meaning as R1\t are prepared by acylation of the compounds of the second general formula above.  2 - Phenyl - 3,5 - dioxo - 7 - chloro - 2,3,4,5-tetrahydro-1, 4-benzoxazepine is prepared by cyclization of a -phenyl-a -(21-carbamyl-41-chlorophenoxy)-acetic acid obtained from the corresponding ethyl ester which is itself prepared from 5-chlorosalicylic acid and ethyl a -chlorophenylacetate. Pharmaceutical compositions, in conventional form for oral or parenteral administration or feedstuff additives comprise a compound of the first general formula above or a salt thereof and an excipient or foodstuff.
BACKGROUND: Rates of venous thromboembolism (VTE) are increasing in people with cystic fibrosis (PwCF). Providers treating VTE in PwCF have reported low confidence concerning anticoagulant drug selection, dose, duration, and drug-drug interactions. As there are currently no published reports regarding management of VTE in PwCF, our objective was to describe the management of VTE in PwCF.
METHODS: PwCF and VTE at the University of Utah Health were identified through electronic medical record searches. Patients were categorized into one of three treatment groups: warfarin, direct oral anticoagulant (DOAC), and low molecular weight heparin (LMWH). The primary outcome was episodes of major bleeding. Secondary outcomes included clinically relevant nonmajor (CRNM) bleeding.
RESULTS: Nine PwCF with a total of 12 unique VTE episodes were included in the study, with all but one episode associated with a peripherally inserted central catheter (PICC). Of the 12 VTE cases, 25% were treated with warfarin, 50% with a DOAC, and 25% with LMWH. There were no episodes of major bleeding and only one episode of CRNM bleeding (Hemoptysis) in the LMWH group. All anticoagulant doses and durations generally followed guidelines for persons without CF. DOACs were the most common VTE treatment, at doses and duration consistent with guidelines for persons without CF, with no major or CRNM bleeding.
CONCLUSION: VTE treatment in PwCF is generally consistent with guidelines for persons without CF with low rates of bleeding. DOACs are a potential option for treatment of VTE in PwCF, but more research is needed.
TQB3616 capsules 180 mg given orally, once daily in 28-day cycle. Fulvestrant injection was given at a fixed dose of 500mg on day 1, day 15 of the first cycle and day 1 of each subsequent cycle, and each cycle is 28 days.
The invention discloses compositions, methods and kits for use in treatment of diseases associated with CNS inflammation such as multiple sclerosis. The composition includes therapeutically effective amount of (1-H indazole-4yl-)methanol. Further, a method of inhibiting glial maturation factor beta (GMF-β) phosphorylation activity in cells is disclosed. The method of treating subjects includes administering a therapeutic effective amount of the composition. The administered composition suppresses the activity of the overexpressed GMF-β either by binding or blocking its phosphorylating sites and ameliorating the inflammatory condition. The disclosed compositions, methods and kits may be used in the treatment of diseases like multiple sclerosis, Alzheimer's disease, Parkinson's disease or cancer.
<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use effective for amelioration of skin troubles accompanied by aging such as skin somberness or the like.  <P>SOLUTION: The invention relates to the skin care preparation for external use (1) for amelioration of skin somberness comprising following (A)-(D). (A) An extract of Mori Cortex. having a tyrosinase activity inhibiting action. (B) A cell-activating agent. (C) An active oxygen scavenger. (D) An estrogenic agent. (2) The cell-activating agent (B) comprises at least one selected from a deoxyribonucleic acid salt, disodium adenosine triphosphate, yeast extract, carrot extract, garlic extract and chlorella vulgaris extract, and the active oxygen scavenger (C) comprises at least one selected from Sanguisorba officinalis extract, tea extract, Moutan Cortex extract and Olea europaea leaf extract, and the estrogenic agent (D) comprises at least one selected from soy Glycine maxes extract, Puerariae Radix extract, Pueraria mirifica extract and Trifolium pretense extract.  <P>COPYRIGHT: (C)2006,JPO&NCIPI
PURPOSE:To provide the subject derivative useful for the prevention and treatment of thrombosis. CONSTITUTION:The compound of formula I (R1 and R2 are hydrocarbon residue; R3 is sulfo or phosphono; CO-R4 is esterified carboxyl, amidated carboxyl, etc.; the wavy line represents the absolute configuration R or S) or its salt, e.g. 2,3-di-O-benzyl-5-O-phospho-D-glucosaccharoascorbic acid n-octadecane thiol ester sodium salt. The compound of formula I can be produced e.g. by producing a compound of formula II from a saccharoascorbic acid derivative, reacting the obtained compound of formula II or its salt with a reactive derivative of sulfuric anhydride such as sulfuric anhydride-pyridine in an inert solvent such as dioxane at 0-40 deg.C, extracting the reactional mixture with a solvent and separating and purifying the extraction product.
493,389. Moving signs. PAGE DISPLAYS, Inc. Aug. 11, 1937, No. 22096. Convention date, Sept. 24, 1936. [Class 3 (i)] A plurality of independent display bands, each carried on a spring roller, are circulated around a closed path, and are extended for viewing each as it reaches a window. The rollers 31 are mounted on brackets 33, the pintle entering a boss 34 and a cross-bar 40 at the free end of the band lying in a notch 39. The brackets 33 have slots which ride over a rail 60, and the cross-bars 40 have end-slots which engage an outer parallel rail 61. Two continuously moving parallel chains 24 carry each a freely hanging hook 26, the rear of which bears against a track 62 which is shaped so as to allow the hooks at certain parts of their path to fall back and at other parts to force the hooks forward to engage projections on the cross-bar 40 and/or the bracket bosses 34. The bend at 62c presses the hooks out to take under the bracket carrying the roller the band of which has just been displayed and under the cross-bar 40 of the following band. The displayed band is thus rolled up, and the following band gradually unrolled, the roller of the following band being retained by coaxial notched discs 18 rotated slowly by gearing. A bend 62D allows the hooks 26 to recede from the cross-bar 40 of the newly-displayed sheet and leave it held by springs 70, while the hooks carry the preceding roller around the track till it lies on the remaining rollers piled on one another, the track 62 bending away at 62F to permit the hooks to fall back. Rails 80 round the bottom keep the hooks 26 off the brackets in that region, and tensioning springs 82 extending from these rails bear against the chains 24. The cross-bar 40 is built up of two parts, one of which is resilient and is attached to the band free edge, and the other of which has a perforated projection entering a central hole in the first part and held therein by a staple, the two parts thus having a pivotal connection with one another which allows the band to adjust itself in winding on and off its roller.
There have been no reported overdosages with Astelin® Nasal Spray. Acute overdosage by adults with this dosage form is unlikely to result in clinically significant adverse events, other than increased somnolence, since one bottle of Astelin® Nasal Spray contains 30 mg of azelastine hydrochloride. Clinical studies in adults with single doses of the oral formulation of azelastine hydrochloride (up to 16 mg) have not resulted in increased incidence of serious adverse events. General supportive measures should be employed if overdosage occurs. There is no known antidote to Astelin® Nasal Spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in young children. Accordingly, Astelin® Nasal Spray should be kept out of the reach of children. Oral doses of 120 mg/kg and greater (approximately 460 times the maximum recommended daily intranasal dose in adults and children on a mg/m2 basis) were lethal in mice. Responses seen prior to death were tremor, convulsions, decreased muscle tone, and salivation. In dogs, single oral doses as high as 10 mg/kg (approximately 260 times the maximum recommended daily intranasal dose in adults and children on a mg/m2 basis) were well tolerated, but single oral doses of 20 mg/kg were lethal.
PROBLEM TO BE SOLVED: To improve surface activity by using purified water, treating the water with magnetic fluxes, and controlling the surface tension to be a specified value or lower. SOLUTION: At first, purified water is produced. As a method for purifying water, for example, an ion exchange method may be employed but the method is not restricted. Magnetic flux treatment, weak current treatment, high voltage treatment, etc., may be employed solely or in combination with one another as the treatment method of the water. Magnetic flux treatment, for example, is normally carried out by passing water at a specified flow speed or higher through a gap between permanent magnets or electromagnets having magnetic field strength about 0.07T(tesla) or higher. Water having surface tension at least 72.8dyn/cm<-1> , that is 71dyn/cm<-1> , 70dyn/cm<-1> , preferably 68.8dyn/cm<-1> or lower than these values can be obtained by treating the purified water by such a method.  Consequently, the obtained water has improved surface activity due to the low surface tension and can be used as a substitute of a surfactant or used together with another surfactant.
Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. SIGNIFICANCE STATEMENT: This work describes that the composition of gut microbiota is altered in mouse pregnane X receptor (PXR) agonist pregnenolone 16α-carbonitrile (PCN)-induced hepatomegaly. Treatment with an antibiotic cocktail depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Additionally, fecal microbiota transplantation from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and yes-associated protein activation.
Tablets with increased active ingredient release contain, as active ingredients thereof, a mixture of L-3,4-dihydroxy- -phenylalanine and L-alpha-hydrazino-methyl-3,4-dihydroxyphenyl propionic acid, particular substituents having the weight ratio of 3 - 12 : 1. A method of their preparation resides in admixing any of L-3,4-dihydroxyphenylalanine and L-alpha-hydrazino- -alpha-methyl-3,4-dihydroxyphenyl propionic acid, or both of them, with a hydrophilic diluent, preferably with lactose and/or microcrystalline cellulose, and optionally with coloring agents. Thus obtained mixture is admixed with auxiliary agents conventionally used for the preparation of tablets and optionally with the other active ingredient, moreover with a solution of stearin in an organic solvent, preferably in alkanol having 2 - 4 carbons. Thus obtained mixture is dried and granulated, optionally admixed with further auxiliary agents. Said mixture is compressed into tablets containing 50 - 70 percent by weight of the active substance, and, if desired, the tablets are film-coated. The process according to the invention provides tablets of appropriate quality with rapid active ingredient release.
This observational cohort study will include patients initiating treatment with ticagrelor 60 mg after a myocardial infarction (MI), and describe their patient characteristics and persistence to treatment. To contextualise the characteristics of the ticagrelor patients, two reference cohorts will be created, including patients treated with another P2Y12 inhibitor than ticagrelor (clopidogrel, prasugrel, or ticlopidine), and patients not treated with any P2Y12 inhibitor, within a comparable timepoint from an MI as for the ticagrelor 60 mg patients. If the a priori threshold of 5,000 person-years on treatment with ticagrelor 60 mg is met, to ensure sufficient precision, outcome events (bleeding and cardiovascular events) will also be analysed and described. Outcome events will only be described in the ticagrelor cohorts; no comparison of outcomes will be made between the ticagrelor and the reference cohorts.

The primary outcome is bleeding requiring hospitalisation. The secondary outcomes include components of the primary outcome, and cardiovascular outcomes. Persistence to treatment with ticagrelor 60 mg will also be assessed The study will be performed in the US and 4 European countries (Sweden, United Kingdom, Italy, Germany).
The efficacy and safety of KALYDECO in patients with CF who have an R117H mutation in the CFTR gene were evaluated in a randomized, double-blind, placebo-controlled, parallel-group clinical trial (Trial 5). Fifty-nine of 69 patients completed 24 weeks of treatment. Two patients discontinued and 8 patients did not complete treatment due to study termination. Trial 5 evaluated 69 clinically stable patients with CF who were 6 years of age or older (mean age 31 years). Patients who were 12 years and older had FEV1 at screening between 40-90% predicted, and patients who were 6-11 years of age had FEV1 at screening between 40-105% predicted. The overall mean FEV1 was 73% predicted at baseline (range: 33% to 106%). The patients had well preserved BMIs (mean overall: 23.76 kg/m2) and a high proportion were pancreatic sufficient as assessed by a low rate of pancreatic enzyme replacement therapy use (pancreatin: 11.6%; pancrelipase: 5.8%). Patients who had persistent Burkholderia cenocepacia, Burkholderia dolosa, or Mycobacterium abscessus isolated from sputum at screening, and those with abnormal liver function defined as 3 or more liver function tests (ALT, AST, AP, GGT, total bilirubin) ≥3 times the ULN, were excluded.

Patients were randomized 1:1 to receive either 150 mg of KALYDECO (n=34) or placebo (n=35) every 12 hours with fat-containing food for 24 weeks in addition to their prescribed CF therapies.

The primary efficacy endpoint was improvement in lung function as determined by the mean absolute change from baseline in percent predicted FEV1 through 24 weeks of treatment. The treatment difference for absolute change in percent predicted FEV1 through Week 24 was 2.1 percentage points (analysis conducted with the full analysis set which included all 69 patients) and did not reach statistical significance (Table 7).

Other efficacy variables that were analyzed included absolute change in sweat chloride from baseline through Week 24, improvement in cystic fibrosis respiratory symptoms through Week 24 as assessed by the CFQ-R respiratory domain score (Table 7), absolute change in body mass index (BMI) at Week 24, and time to first pulmonary exacerbation. The overall treatment difference for the absolute change from baseline in BMI at Week 24 was 0.3 kg/m2 and the calculated hazard ratio for time to first pulmonary exacerbation was 0.93, which were not statistically significant.

Statistically significant improvements in clinical efficacy (FEV1, CFQ-R respiratory domain score) were seen in several subgroup analyses and decreases in sweat chloride were observed in all subgroups. The mean baseline sweat chloride for all patients was 70 mmol/L. Subgroups analyzed included those based on age, lung function, and poly-T status (Table 7).
Patients wear the home sleep apnea machine overnight. Patients undergoing standard of care CRT wear the home sleep apnea machine a second time 3 months after completion of CRT.
The present application is directed towards compounds, pharmaceutically acceptable salts or prodrugs thereof, which are inhibitors of Histone Deacetylase (HDAC) binding or function. The compounds especially may have some selectivity for inhibiting Class IIa versus Class I HDACs. The present application also relates to methods of using the compounds and to uses of the compounds, especially in relation to the prevention of a disease, disorder or condition associated with Class IIa HDAC activity. In one form, the compounds are (ortho-phenyl) phenyl hydroxamates. In another form, the compounds are as provided in Formula (I), wherein R1 is a phenyl or cycloalkenyl which may be optionally substituted. Formula (I)
Cysteine hydrochloride injection, USP contains aluminum that may be toxic.

Aluminum may reach toxic levels with prolonged parenteral administration in patients with renal impairment. Neonates and preterm infants are particularly at risk for aluminum toxicity because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which also contain aluminum.

Patients with renal impairment including neonates and preterm infants, who receive greater than 4 to 5 mcg/kg/day of parenteral aluminum can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Exposure to aluminum from cysteine hydrochloride injection, USP is not more than 0.25 mcg/kg/day when preterm and term neonates are administered the recommended maximum dosage of cysteine hydrochloride injection, USP (22 mg cysteine hydrochloride/g of amino acids and 4 g of amino acids/kg/day) [see Dosage and Administration (2.5)]. When prescribing cysteine hydrochloride injection, USP for use in parenteral nutrition containing other small volume parenteral products, the total daily patient exposure to aluminum from the admixture should be considered and maintained at no more than 5 mcg/kg/day [see Use in Specific Populations (8.4)].
An appliance for the delivery of at least one bioactive agent to the eye has at least one diffusion attenuator within a hydrophilic or silicone-hydrogel contact lens. The bioactive agent can be a drug or a nutraceutical. The diffusion attenuator can be a plurality of solid particles or phase separated liquid aggregates within at least one continuous phase of the lens where the diffusion attenuators promote a tortuous path for the diffusion of the bioactive agent to mediate the rate by which the bioactive agent diffuses from the contact lens. The diffusion attenuator can be homogeneously dispersed throughout at least one continuous phase of the lens to modify the diffusivity of the bioactive agent through that phase. The diffusion attenuator can have little or no affinity for the bioactive agent or can be miscible with the bioactive agent. The diffusion attenuator can be incorporated while forming the contact lens by polymerization of a monomer mixture containing the diffusion attenuator. For liquid diffusion attenuators, the liquid can be co-absorbed with a solvent into the lens followed by removal of the solvent, where the bioactive agent can be co-absorbed or subsequently absorbed after the loading of the diffusion attenuator. The diffusion attenuator can be Vitamin E.
Rare genetic diseases, often referred to as orphan diseases due to their low prevalence and limited treatment options, have long posed significant challenges to our medical system. In recent years, Messenger RNA (mRNA) therapy has emerged as a highly promising treatment approach for various diseases caused by genetic mutations. Chemically modified mRNA is introduced into cells using carriers like lipid-based nanoparticles (LNPs), producing functional proteins that compensate for genetic deficiencies. Given the advantages of precise dosing, biocompatibility, transient expression, and minimal risk of genomic integration, mRNA therapies can safely and effectively correct genetic defects in rare diseases and improve symptoms. Currently, dozens of mRNA drugs targeting rare diseases are undergoing clinical trials. This comprehensive review summarizes the progress of mRNA therapy in treating rare genetic diseases. It introduces the development, molecular design, and delivery systems of mRNA therapy, highlighting their research progress in rare genetic diseases based on protein replacement and gene editing. The review also summarizes research progress in various rare disease models and clinical trials. Additionally, it discusses the challenges and future prospects of mRNA therapy. Researchers are encouraged to join this field and collaborate to advance the clinical translation of mRNA therapy, bringing hope to patients with rare genetic diseases.