anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention provides a benzenesulfonyl lupetazin derivative, which is obtained by reacting benzenesulfonyl lupetazin with acid and alkali metal elements or an ammonia (ammonium) compound or amino acid or amino alcohol in turn or directly reacting the benzenesulfonyl lupetazin with acid salt. When acid or the acid salt is a sulfate radical, benzenesulfonyl lupetazin complex bisulfate is obtained; and when acid or the acid salt is a phosphate radical, benzenesulfonyl lupetazin complex dihydric phosphate is obtained. A method of the invention has the advantages of reasonable design, stable process and high production practicability. The benzenesulfonyl lupetazin derivative provided by the invention has the remarkable advantages of high solubility, high bioavailability and the like and can be prepared into a preparation. After the preparation is taken orally, benzenesulfonyl lupetazin goes into blood, so that a better effect for treating male erectile dysfunction is achieved. The derivative has the structural formula shown in the specifications.
ABL503 will be administered biweekly of every 28-day cycle in the dose-escalation. The dosing interval to be used in the dose-expansion part will be re-evaluated based on the emerging safety and PK data from the dose-escalation part of the study.
BACKGROUND: Pudendal neuralgia (PN) is a chronic neuropathy that causes pain, numbness, and dysfunction in the pelvic region. The current state-of-the-art treatment is pulsed radiofrequency (PRF) in which a needle is supposed to be placed close to the pudendal nerve for neuromodulation. Given the effective range of PRF of 5 mm, the accuracy of needle placement is important. This study aimed to investigate the potential of augmented reality guidance for improving the accuracy of needle placement in pulsed radiofrequency treatment for pudendal neuralgia.
METHODS: In this pilot study, eight subjects performed needle placements onto an in-house developed phantom model of the pelvis using AR guidance. AR guidance is provided using an in-house developed application on the HoloLens 2. The accuracy of needle placement was calculated based on the virtual 3D models of the needle and targeted phantom nerve, derived from CBCT scans.
RESULTS: The median Euclidean distance between the tip of the needle and the target is found to be 4.37 (IQR 5.16) mm, the median lateral distance is 3.25 (IQR 4.62) mm and the median depth distance is 1.94 (IQR 7.07) mm.
CONCLUSION: In this study, the first method is described in which the accuracy of patient-specific needle placement using AR guidance is determined. This method could potentially improve the accuracy of PRF needle placement for pudendal neuralgia, resulting in improved treatment outcomes.
The present invention provides a face mask capable of being difficult to cause wrinkles, twisting, or loosening due to movement of a mouth or a jaw by maintaining a feature which is easily fitted to a face and lifting skin of cheeks or the mouth. The face mask (1) comprises: a sheet member (2) which is formed of a nonwoven fabric or a woven fabric; and a skin caring agent (3) which is applied to the sheet member. The sheet member includes an upper member (11) and a lower member (12) which are separated to each other and are positioned in an upper side and a lower side of an up/down direction on the sheet member. The lower member includes a pair of lower earring holes (24, 24) for earrings in both end units of a horizontal direction. When the face mask is mounted on a wearer, the upper member covers an area from the mouth to a forehead of the wearer in the up/down direction. The lower member is separated from the upper member and covers an area from the jaw and the mouth of the wearer to a pair of ear rims by hanging the pair of lower earring holes in both ears.
The oocytes obtained from the patients allocated to this group will be subdivided again in two groups Group 2a: Oocytes treated with A23187 (treatment). Group 2b: Oocytes that will not be treated with any activator (Control).
The intervention include 12 face-to-face group sessions of 45 minutes each, twice a week for 6 weeks. The intervention include OEP-based techniques only. At the end of the sessions, participants will be instructed to perform nine exercises independently at home, at a minimum of twice per week for six months.
The origins of colorectal cancer have long been a subject of intense debate. Early observations noted cancer formation in the human gut slightly above the base of crypts, the structural and functional units of the regenerative compartment of the intestinal epithelium. This suggested that the cells of origin for colorectal cancer reside close to the crypt-villus junction, where more differentiated cells are located. However, the specific induction of early cancer-initiating mutations within differentiated cells failed to initiate cancer. The subsequent identification of long-lived Lgr5+ intestinal stem cells and investigations into their role in cancer development further shifted the earlier views, leading to the widely accepted theory that colorectal cancer arises from stem cells and progenitors located at the base of crypts. A recent study published in Nature Genetics by Mathijs P. Verhagen and colleagues challenges this paradigm, providing compelling evidence that differentiated nonstem cell lineages, particularly Paneth cells, can serve as a source of intestinal tumorigenesis, especially in the context of inflammation and the consumption of a Western-style diet. This work significantly advances our understanding of the colorectal cancer initiation process and provides a new paradigm that may explain the increasingly higher incidence of colorectal cancer in younger people.
FIELD: chemistry.SUBSTANCE: invention relates to an improved method for preparing avatrombopag or maleate thereof. Compound corresponds to the following structural formula (I), has the properties of a thrombopoietin receptor agonist (aTPO-r) and can be used for treating thrombocytopenia.(1)Method comprises adding dropwise Brto solution of 2-acetyl-4-chlorothiophene (1) in diethyl ether, extraction is carried out with ethyl ether of acetic acid (EtOAc), the residue is dissolved in ethyl alcohol, thiourea is added and subjected to boiling. Resulting residue is dissolved in a mixture of EtOAc/hexane, having ratio by volume of 1:1, dropped after cooling to room temperature, filtered precipitate of 4-(4-chlorothiophen-2-yl)thiazole-2-amine (2) is washed with a mixture of EtOAc/hexane and dried in a vacuum at room temperature, is dissolved in dioxane and N-bromosuccinimide is added to obtain 4-(4-chlorothiophen-2-yl)thiazole-4-bromo-2-amine (3), as well as a characteristic impurity of 5-bromo-4-(5-bromo-4-chlorothiophen-2-yl)thiazole-2-amine, which then reacts similarly to (3), dissolving the product in acetonitrile, adding 1-cyclohexylpiperazine and triethylamine, carrying out reaction during boiling. Precipitate of 4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazole-2-amine (4) precipitated during cooling is filtered, washed with water, hexane and diethyl ether and dried, the obtained product is added to pyridine solution of 5-chloro-6-(4-ethoxycarbonyl)piperidin-1-yl)nicotinic acid (7), which is obtained by adding to the solution of ethyl-piperidine-4-carboxylate (5) in dimethylsulphoxide 5,6-dichloronicotinic acid (6) and triethylamine, followed by heating to temperature of 150 °C, crystallization, washing with water, hexane, drying at room temperature and dissolving (7) in pyridine. Then cooled solution of mixture (4) and (7) is added with phosphorus oxychloride (POCl) so that mixture temperature does not exceed 10 °C is heated to room temperature, crystallization reaction is carried out, obtained crystalline precipitate of ethyl ether of avatrombopag (8) is washed with water and hexane, the powder is dried, dissolved in a mixture of toluene and ethyl acetate, having ratio by volume of 10 to 1, purified by flash chromatography on silica gel, suspended in a mixture of distilled water and tetrahydrofuran, adding sodium hydroxide at room temperature, stirring, diluting with water, adding acetic acid to the obtained solution until pH=5–5.5, stirring at room temperature until crystallization ends and precipitation of avatrombopag (9). Obtained precipitate is filtered and washed with water, a mixture of tetrahydrofuran and water, then with water, hexane and ethyl acetate, and dried with subsequent treatment of the obtained product with maleic acid to obtain maleate of avatrombopag.EFFECT: method enables to exclude heating during hydrolysis of ether, significantly reduce the characteristic impurity of 5-bromo-4-(5-bromo-4-chlorothiophen-2-yl)thiazole-2-amine to trace amounts and improve purification of the obtained intermediate compounds; yield of the obtained product is 94,5 %, purity is 98 % NMR.1 cl, 3 ex
Trunk control involves integration of sensorimotor information in the brain. Individuals with chronic low back pain (cLBP) have impaired trunk control and show differences in brain structure and function in sensorimotor areas compared with healthy controls (HC). However, the relationship between brain structure and trunk control in this group is not well understood. This cross-sectional study aimed to compare seated trunk control and sensorimotor white matter (WM) structure in people with cLBP and HC and explore relationships between WM properties and trunk control in each group. Thirty-two people with cLBP and 35 HC were tested sitting on an unstable chair to isolate trunk control; performance was measured using the 95% confidence ellipse area (CEA95) of center-of-pressure tracing. A WM network between cortical sensorimotor regions of interest was derived using probabilistic tractography. WM microstructure and anatomical connectivity between cortical sensorimotor regions were assessed. A mixed-model ANOVA showed that people with cLBP had worse trunk control than HC (F = 12.96; p < .001; ηp2 = .091). There were no differences in WM microstructure or anatomical connectivity between groups (p = 0.564 to 0.940). In the cLBP group, WM microstructure was moderately correlated (|r| = .456 to .565; p ≤ .009) with trunk control. Additionally, the cLBP group demonstrated stronger relationships between anatomical connectivity and trunk control (|r| = .377 to .618 p < .034) compared to the HC group. Unique to the cLBP group, WM connectivity between right somatosensory and left motor areas highlights the importance of interhemispheric information exchange for trunk control. Parietal areas associated with attention and spatial reference frames were also relevant to trunk control. These findings suggest that people with cLBP adopt a more cortically driven sensorimotor integration strategy for trunk control. Future research should replicate these findings and identify interventions to effectively modulate this strategy.
PURPOSE: A method of producing the extract of Rhus verniciflua having pharmacological efficacy without causing allergic reactions by reextraction of the extract of Rhus verniciflua in water or spirits is provided. The extract has excellent pharmacological efficacy. CONSTITUTION: Rhus verniciflua is extracted in a solvent such as a mixture of water and spirits having an ethanol content of 0 to 90% at 30 to 95deg.C and then filtered. The filtrate is concentrated to give solids and the solids are added to 10 to 100 times of 95 to 99.5% ethanol, filtrated and then concentrated to remove the solvent. The concentrate is added with 1 to 30 times of hexane to remove hexane-soluble components, added 1 to 50 times of water and then extracted to remove water-soluble components, followed by concentration and freeze-drying. The extract has anticancer effect, antimetastatic effect, reverse transcriptase inhibitory activity and antioxidant effect while increasing the mobility and number of sperms.
Renal toxicity ranging from elevated serum creatinine to renal failure and death have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for non-MDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to <20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium <3 mEq/L) developed in 5 patients with CML treated with azacitidine and etoposide. Monitor serum creatinine and electrolytes prior to initiation of therapy and with each cycle. If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, reduce or hold the dose [see Dosage and Administration (2.6)].

Patients with renal impairment may be at increased risk for renal toxicity. Also, azacitidine and its metabolites are primarily excreted by the kidney. Therefore, monitor these patients closely for toxicity [see Dosage and Administration (2.6, 2.7)]. Patients with MDS and renal impairment were excluded from the clinical studies. 

Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
BACKGROUND: Specialized pro-resolving mediators (SPMs) promote resolution of inflammation, clear infections and stimulate tissue regeneration. These include resolvins, protectins, and maresins. During self-resolving acute inflammation, SPMs are produced and have key functions activating endogenous resolution response for returning to homeostasis. Herein, we addressed whether infections initiated with ongoing inflammation alter resolution programs, and if low-dose repetitive SPM regimen re-programs the resolution response.
METHODS: Inflammation was initiated with zymosan (1 mg/mouse) followed by E. coli (105 CFU/mouse) infections carried out in murine peritonitis, and exudates collected at 4-72 h. Leukocytes were enumerated using light microscopy, percentages of PMN, monocytes and macrophages were determined using flow cytometry, and resolution indices calculated. Lipid mediators and SPM profiles were established using mass spectrometry-based metabololipidomics. Repetitive dosing with a SPM panel consisting of RvD1, RvD2, RvD5, MaR1 and RvE2 (0.1 ng/mouse each, i.p.) was given to mice, followed by zymosan challenge. Leukocyte composition, resolution indices and RNA-sequencing were carried out for the repetitive SPM treatments.
RESULTS: E. coli infections initiated acute inflammation-resolution programs with temporal SPM production in the infectious exudates. Zymosan-induced inflammation prior to E. coli peritonitis shifted exudate resolution indices and delayed E. coli clearance. Lipid mediator metabololipidomics demonstrated that E. coli infection with ongoing zymosan-induced inflammation shifted the time course of exudate SPMs, activating a SPM cluster that included RvD1, RvD5 and MaR1 during the initiation phase of infectious inflammation (0-4 h); RvD5 and MaR1 were present also in the resolution phase (24-48 h). To emulate daily SPM regimens used in humans, a repetitive subthreshold dosing of the SPM panel RvD1, RvD2, RvD5, MaR1 and RvE2 each at 0.1 ng per mouse was administered. This low-dose SPM regimen accelerated exudate PMN clearance following zymosan-induced inflammation, and shortened the resolution interval by > 70%. These low-dose SPMs regulated genes and pathways related to immune response, chemokine clearance and tissue repair, as demonstrated by using RNA-sequencing.
CONCLUSIONS: Infections encountered during ongoing inflammation in mice reset the resolution mechanisms of inflammation via SPM clusters. Low-dose SPMs activate innate immune responses and pathways towards the resolution response that can be reprogrammed.
Risk Summary

MESNEX is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide is excreted in breast milk. Refer to the ifosfamide prescribing information for more information on use during lactation. There are no data on the presence of mesna in human or animal milk, the effect on the breastfed child, or the effect on milk production. 

MESNEX injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4)].

Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 1 week after the last dose of MESNEX or ifosfamide.
Prolonged action corticotrophin preparations comprise an aqueous suspension of a water-in-soluble zinc - corticotrophin - gelatine - tannate complex which is prepared by adding, in any order, aqueous solutions of a zinc salt, tannic acid and partially hydrolysed (e.g. by autoclaving in aqueous solution thereof) gelatine to an aqueous solution of corticotrophin.  The preparations may contain from 20 to 500 USP subcutaneous units per ml. of corticotrophin and from 0.1 to 2.5 mg. of tannic acid, from 6 to 60 mg. of partially hydrolysed gelatine and at least 0.25 mg. of zinc per 100 units of corticotrophin.  The pH of the preparations is desirably between 4 and 8 and is preferably about 5.  The corticotrophin used is preferably derived from porcine or bovine pituitary and may be of high or low potency and may be present in the preparations both as the insoluble complex and in solution.  If corticotrophin derived from bovine pituitary is used, the gelatine may be omitted and an insoluble zince - corticotrophin - tannate complex results.  Optional ingredients mentioned are cysteine (stabilizer) and antibacterial agents e.g. methyl and propyl p-aminobenzoates and phenol.  The preparations may be lyophilized e.g. by freeze-drying.
The Sharing History through Active Reminiscence and Photo-imagery (SHARP) Program is a recently developed culturally celebratory, multimodal approach to physical, social, and reminiscence activity. The SHARP walking application, accessed on a group tablet, is preloaded with 72 themed, 1-mile neighborhood routes with GPS-linked "Memory Markers," historical neighborhood images and questions, to prompt conversational reminiscence about Black life, history, and culture. In this Stage I study, walking triads consist of a healthy or mildly cognitively impaired (MCI) primary dementia caregiver (aged 55+), the care partner - a person living with early-stage dementia (PLWD) or MCI (aged 55+), and a healthy or MCI caregiver support person (aged 18+). Triads walk 3x/week over 16 weeks in the gentrifying, historically Black neighborhoods of Portland, Oregon. The primary caregiver wears an actigraphy watch, uses an under-the-mattress sleep sensor, and on a weekly basis, measures weight on a study-provided digital scale and completes a health update survey. Watch, sleep sensor, and weekly measures are optional for the PLWD. We aim to (1) adapt SHARP implementation, technology, and protocol for caregivers of PLWD, and (2) test preliminary efficacy of this intervention on dementia caregivers' physical and mental health.
Recent developments in exploring the biological enzyme mimicking properties in nanozymes have opened a separate avenue, which provides a suitable alternative to the natural antioxidants and enzymes. Due to high and tunable catalytic activity, low cost of synthesis, easy surface modification, and good biocompatibility, nanozymes have garnered significant research interest globally. Several inorganic nanomaterials have been investigated to exhibit catalytic activities of some of the key natural enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, peroxidase, and oxidase, etc. These nanozymes are used for diverse biomedical applications including therapeutics, imaging, and biosensing in various cells/tissues and animal models. In particular, inflammation-related diseases are closely associated with reactive oxygen and reactive nitrogen species, and therefore effective antioxidants could be excellent therapeutics due to their free radical scavenging ability. Although biological enzymes and other artificial antioxidants could perform well in scavenging the reactive oxygen and nitrogen species, however, suffer from several drawbacks such as the requirement of strict physiological conditions for enzymatic activity, limited stability in the environment beyond their optimum pH and temperature, and high cost of synthesis, purification, and storage make then unattractive for broad-spectrum applications. Therefore, this review systematically and comprehensively presents the free radical-mediated evolution of various inflammatory diseases (inflammatory bowel disease, mammary gland fibrosis, and inflammation, acute injury of the liver and kidney, mammary fibrosis, and cerebral ischemic stroke reperfusion) and their mitigation by various antioxidant nanozymes in the biological system. The mechanism of free radical scavenging by antioxidant nanozymes under in vitro and in vivo experimental models and catalytic efficiency comparison with corresponding natural enzymes has also been presented.
A multi-center, single-arm, open-label study was conducted in 28 girls with McCune-Albright Syndrome and progressive precocious puberty aged 2 to <10 years. All patients received a 1 mg daily dose of anastrozole. The trial duration was 12 months. Patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) McCune-Albright Syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. Patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean Tanner stage for breast of 2.7 ± 0.81. Compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). There were no clinically significant changes in Tanner staging, mean ovarian volume, mean uterine volume and mean predicted adult height. A small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in McCune-Albright Syndrome patients. 

Five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole. These were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis.
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
This small-scale study of the feasibility of a BCI to operate the tilt position of a power wheelchair was also designed to determine the conditions and support structures necessary for use of a BCI in the home. In this study, people with Amyotrophic Lateral Sclerosis (ALS) will have a BCI in their home. They will receive training in order to operate and maintain the BCI. The BCI will allow them to access at least one task of primary interest to them. Task may include communication, computer access, control of assistive technology, or control of wheelchair seat position. Data concerning the use of the BCI will be collected throughout the study. Custom installations will be made for each participant to connect to their wheelchair and provide communication options if needed. Each installation is expected to be a unique prototype because of the differing control requirements for the individual wheelchairs in use by the participants.

We intended to enroll six participants, but were only able to enroll one.