anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Inclusion body myositis (IBM) is a progressive, debilitating muscle disease commonly encountered in patients over the age of 50. IBM typically presents with asymmetric, painless, progressive weakness and atrophy of deep finger flexors and/or quadriceps muscle. Many patients with IBM develop dysphagia. However, atypical presentations of IBM with isolated dysphagia, asymptomatic hyper-CKemia, foot drop, proximal weakness, axial weakness, and facial diplegia have been reported. Other acquired and some inherited disorders may present similar to IBM, and this list gets more expansive when considering atypical presentations. In general, disease progression of IBM leads to loss of hand function and impaired ambulation, and most IBM patients become wheelchair dependent within 13-15 years of disease onset. Hence, IBM impacts negatively patients' quality of life and reduces longevity compared to the general population. Acknowledging the complete clinical spectrum of IBM presentation and excluding mimics would shorten the time to diagnosis, lead to prompt initiation of supportive management and avoid unproven therapy. Ongoing advanced phase studies in IBM provide hope that a therapy may soon be available. Therefore, an added potential benefit of early diagnosis would be prompt initiation of disease-modifying therapy once available.
Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg + placebo to match adalimumab 40 mg in addition to a stable dose of MTX for up to 24 weeks. After 24 weeks, participants will be rerandomized to filgotinib 200 mg to receive filgotinib 200 mg + placebo to match filgotinib 100 mg + placebo to match adalimumab 40 mg in addition to a stable dose of MTX.
Pregnancy Category: C

The safety of Trilipix in pregnant women has not been established. There are no adequate and well controlled studies of Trilipix in pregnant women. Trilipix should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When Trilipix is administered with a statin in a woman of childbearing potential, refer to pregnancy category and product labeling for the statin [see Precautions, Pregnancy]. All statins are contraindicated in pregnant women.

In pregnant rats given oral dietary doses of 14, 127, and 361 mg/kg/day from gestation day 6-15 during the period of organogenesis, adverse developmental findings were not observed at 14 mg/kg/day (less than 1 times the maximum recommended human dose [MRHD], based on body surface area comparisons; mg/m2). At higher multiples of human doses evidence of maternal toxicity was observed.

In pregnant rabbits given oral gavage doses of 15, 150, and 300 mg/kg/day from gestation day 6-18 during the period of organogenesis and allowed to deliver, aborted litters were observed at 150 mg/kg/day (10 times the MRHD, based on body surface area comparisons; mg/m2). No developmental findings were observed at 15 mg/kg/day (at less than 1 times the MRHD, based on body surface area comparisons; mg/m2).

In pregnant rats given oral dietary doses of 15, 75, and 300 mg/kg/day from gestation day 15 through lactation day 21 (weaning), maternal toxicity was observed at less than 1 times the MRHD, based on body surface area comparisons; mg/m2.
Twenty patients with recurrent small cell lung cancer who met the inclusion criteria were enrolled in the study after signing an informed consent form. Tumor samples were obtained through clinical puncture, and qualified samples were subjected to organoid modeling. Perform drug sensitivity test on the established lung cancer organoids. The drugs used are all that have been marketed and applied in clinical practice. According to the results of organoid drug sensitivity analysis, the patient received a treatment plan with relatively sensitive drugs. Follow up prognostic data and relevant clinical information of enrolled patients, conduct statistical analysis on the consistency between drug sensitivity test results and patient treatment response, and evaluate the clinical effectiveness of treatment plans guided by organoid drug sensitivity results.
An online video course for 6 weeks. The therapist will provide online video courses 3-5 times a week and record the implementation on the online platform every week. The course includes action plans, two Lateral integration/cross-midline, vestibular system, visual perception, opto-motor integration, eye movements, core strength activities and balance ability, etc.
Enzymes convert capecitabine to 5-fluorouracil (5-FU) in vivo. Both normal and tumor cells metabolize 5-FU to 5-fluoro-2’-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2’-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.
This triple-blind parallel group, randomized clinical trial was conducted at the department of Operative Dentistry and Endodontics, School of Dentistry from April 24, 2024 to September 25, 2024. Participants were randomly distributed into two groups by Lottery method. A consecutive non-probability sampling technique was used. Before initiating treatment, participants were briefed about the intervention and their preoperative pain score was recorded. In both groups, endodontic treatment was initiated under rubber dam isolation. Access opening done and canals explored. Working length taken by radiographic method and reconfirmed by an electronic apex locator. Afterwards, canals were prepared till Master Apical File size F2 (4% Taper). In group A, Nano-reinforced calcium hydroxide medicament was placed while in group B, calcium hydroxide without nanoparticles was utilized. Participants were instructed to rate their postoperative pain record after 4hrs, 24hrs, 48hrs, 72hrs and 96hrs.
Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.
Applying brassinolide (BL, a phytohormone) in combination with pyraclostrobin (Pyr, a fungicide) has shown effective disease control in field trials. However, the mechanism by which BL + Pyr control disease remains uncertain. This work compared the disease control and defense responses of three pretreatments (BL, Pyr, and BL + Pyr) in Arabidopsis thaliana. We found that BL + Pyr improved control against Pyr-sensitive Hyaloperonospora arabidopsidis and Botrytis cinerea by 19 and 17% over Pyr, respectively, and achieved 29% control against Pyr-resistant B. cinerea. Furthermore, BL + Pyr outperformed BL or Pyr in boosting transient H2O2 accumulation, and the activities of POD, APX, GST, and GPX. RNA-seq analysis revealed a more potent activation of defense genes elicited by BL + Pyr than by BL or Pyr. Overall, BL + Pyr controlled disease by integrating the elicitation of plant innate disease resistance with the fungicidal activity of Pyr.
FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes novel derivatives of phenylalkylcarboxylic acid of the formula (I)   where R 1  means alkyl-group with linear or branched chain having from 1 to 6 carbon atoms; R 21  is alkylene group with linear or branched chain having from 2 to 6 carbon atoms; R 3  is hydrogen atom; Z is alkylene group with linear or branched chain having from 1 to 6 carbon atoms; W means: (i) alkyl-group with linear or branched chain having from 1 to 6 carbon atom; (ii) alkoxy- group with linear or branched chain having from 1 to 4 carbon atoms; (iii) alkylthio-group with linear or branched chain having from 1 to 4 carbon atoms; (iv) amino-group; (v) mono- alkylamino-group with linear or branched chain having from 1 to 4 carbon atoms; (vi) dialkylamino-group with linear or branched chain where alkyl-groups are similar or distinct and each group has from 1 to 4 carbon atoms; (vii) N-alkyl-N-aryl- amino-group having alkyl with linear or branched chain having from 1 to 4 carbon atoms and aryl moiety having from 6 to 10 carbon atoms; (viii) arylhydroxy-group having from 6 to 10 carbon atoms that can has one substituent α indicated below, in aryl moiety; (ix) arylthio-group having from 6 to 10 carbon atoms; (x) arylamino-group having from 6 to 10 carbon atoms; (xi) aralkyl-group having from 7 to 12 carbon atoms or (xii) 1-pyrrolyl group; X means aryl-group having from 6 to 10 carbon atoms that can has one substituent α indicated below being substituent α means: (i) alkyl-group with linear or branched chain having from 1 to 6 carbon atoms; (ii) halogenated alkyl- group with linear or branched chain having from 1 to 4 carbon atoms; (iii) halogen atom; (iv) aryl-group having from 6 to 10 carbon atoms and aryl moiety can be substituted with alkoxy- group with linear or branched chain having from 1 to 4 carbon atoms or halogen atom; or (v) pyridyl; Y means oxygen atom, their pharmacologically acceptable salts of pharmacologically acceptable esters. The above indicated new derivatives of phenylalkylcarboxylic acid show high activity in decrease blood glucose level as well as their pharmacologically acceptable salts and pharmacologically acceptable esters. Invention describes also the composition containing indicated compound as an active component used for treatment or prophylaxis of hyperglycaemia, their use for drug preparing used for treatment and prophylaxis of hyperglycaemia. EFFECT: new compounds indicated above, valuable medicinal properties. 30 cl, 68 tbl, 25 ex
Intensively studied participants who are currently participating in the Merck Expanded Access Program and receiving raltegravir. Participants in Group 5 may undergo optional leukapheresis. Group 5 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 5 participants will default to either Group 3 or Group 4.
Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.
The invention comprises compounds of the formula <FORM:0910428/IV (b)/1> and their acid addition salts, in which A stands for a 1-5 membered hydrocarbon chain which may also contain a double bond or be interrupted by a nitrogen atom which may be unsubstituted or substituted by an alkyl or aralkyl group, m represents any one of the numbers from 0 to 6, m1 any one of the numbers from 0 to 3, R and R1 stand for hydrogen or C1-7 alkyl and Z for a primary or secondary amino group, with the proviso that CmH2m separates the bridgehead atoms by at most 2 carbon atoms, and in which <FORM:0910428/IV (b)/2> when A forms a 3-5-membered isocyclic ring with the bridge members and <FORM:0910428/IV (b)/3> when A forms a 4-membered azacyclic ring with the bridge members. The compounds may be prepared, for example, by reducing in compounds of the general formula: <FORM:0910428/IV (b)/4> in which A, m, n, n1, R and R1 have the meanings above and m1 stands for any one of the numbers 1-6, the cyano group to the methyleneamino group preferably by catalytic hydrogenation or with a di-light metal hydride or with aluminium hydride or aluminium borohydride if necessary in the presence of an activator such as aluminium chloride, or for example, by condensing a 1,2-cis-cycloaliphatic dicarboxylic acid anhydride with a lower alkylene diamine and reducing the resulting dioxo compound with a di-light metal hydride.  The aza-bicycloalkyl-(N)-alkyl cyanides are prepared by condensing the free base of the formula <FORM:0910428/IV (b)/5> with a reactive esterified cyano lower alkanol. b -Hexahydroindolino propionitrile is also prepared from hexahydroindoline and acrylonitrile.  Hexahydroindoline is prepared by reducing 4,7,8,9-tetrahydrophthalimide with lithium aluminium hydride to form 4,7,8,9-tetrahydroindoline which is hydrogenated. Decahydro-3-benzazepine is prepared by acetylating 2,3,4,5-tetrahydro - 3 - benzazepine, hydrogenating the 3-acetyl-2,3,4,5-tetrahydro-3-benzazepine to a mixture of the decahydro free base and 3-acetyl-decahydro-3-benzazepine and hydrolysing the acetyl compound.  N-methyl-bispidine is prepared by reacting bispidine with methyl formate to give N-formyl bispidine which is reduced with lithium aluminium hydride.
The invention relates to an essence-securing and spermatorrhea-suppressing stamen nelumbinis drink and a preparation method thereof. The essence-securing and spermatorrhea-suppressing stamen nelumbinis drink is characterized by carefully selecting herbaceous plant elite components with reasonable compatibility. Effective components of the formula of the drink comprise rehmannia glutinosa, cornus officinalis, Chinese yam, poria cocos, cortex moutan, oriental waterplantain rhizome, os draconis, and stamen nelumbinis. According to the pharmaceutical value of the stamen nelumbinis in the invention, the stamen nelumbinis is compounded with various kinds of Chinese herbal medicine to develop a better curative effect. The formula is free of any chemical component, the compatibility is strictly screened through experiments, and the compound has a good effect. The drink is prepared through a special process, is stable in quality, and has obvious improvement on organism immunity. The drink is particularly suitable for sub-healthy people who have reproductive system trouble resulting from the deficiency of the liver and the kidney, and for the middle-aged, the elder and the weak, who often feel lack of energy and suffer from somnolence and lack of physical strength, soreness and weakness of waist and knees, and inability to sleep and night sweating.
OBJECTIVE: China has a substantial disease burden of cervical cancer. To further understand preventive measures for reducing cervical cancer in China, this study aimed to correlate screening attendance and regular screening with human papillomavirus (HPV) vaccination among Chinese females.
METHODS: This prospective questionnaire-based survey recruited Chinese females aged 25 or above in Hong Kong by random digit dialing telephone interviews in 2022. The survey studied women's practice of cervical screening and adherence to regular screening. Variables including HPV vaccination status and attendance of physical check-ups were involved in the questionnaire. Screening uptake and screening adherence were the main outcomes, which were measured as the proportion of women who reported having attended a cervical screening and screened regularly, respectively.
RESULTS: Out of 906 valid respondents, the reported cervical screening uptake was over 70% among females aged 30 or above and particularly over 80% among women aged 35-59; however, the uptake was only 46% among those aged 25-29. Adherence to regular screening was 50%-60% across ages 25-59 years and dropped to approximately 40% for women older than 60 years. Both screening uptake and adherence were associated with HPV vaccination, with adjusted odds ratios of 2.37 and 2.23, respectively. A large proportion of regularly screened women may be overscreened for screening more frequently than recommended.
CONCLUSION: Responded Chinese females showed good cervical screening uptake but were moderately adherent to regular screening. Policymakers should emphasize the importance of regular screening and the recommended screening frequency by HPV vaccination status for better healthcare resource use.
At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5β1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.
Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.
INTRODUCTION: Ultrasound-guided quadratus lumborum block and erector spinae plane block are widely used for postoperative analgesia in adult patients undergoing abdominal surgeries. This protocol aims to compare the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries.
METHODS AND ANALYSIS: Four databases, including PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), will be searched. Randomised controlled trials that compared the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in adult patients will be identified. The primary outcomes are time to the first analgesic request and postoperative analgesic consumption over 24 hours. Secondary outcomes will include postoperative pain scores and the incidence of side effects. RevMan V.5.3 software will be used for data processing and statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will be used to assess the evidence quality of outcomes.
ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Results of this present study will be submitted to a peer-reviewed journal.
PROSPERO REGISTRATION NUMBER: CRD42023445802.
Aerosol non-aqueous hair-setting compositions comprise an alcoholic solution of a film-forming substance selected from vegetable mucilage modified cellulose derivatives, alginates, polyvinyl pyrrolidones, polyvinyl alcohols, polyacrylates, hydantoin formaldehyde resins and shellac and containing from 1-20% by weight of one or more diols having a molecular weight not exceeding 200 and of which one or both hydroxy groups may be alkylated or acylated. The propellants may be chlorofluoromethanes. The alcohol component may be ethyl or isopropyl alcohol and specified diols include glycol, diethylene diglycol, 1,2-propylene glycol, 1,3- or 2,3-butanediol, ethyl-, propyl-, or butyl-glycol or diglycol, glycol monoacetate or methyl-ethyl-propyl-or butyl-glycol monoacetate and 3-methyl-2,4-pentanediol.  Surface-active agents and perfumes may also be present.ALSO:A non-aqueous hair-setting composition comprises an alcoholic solution of a film-forming substance selected from vegetable mucilage, modified cellulose derivatives, alginates, polyvinyl pyrrolidones, polyvinyl alcohols, polyacrylates, hydantoin formaldehyde resins and shellac and containing from 1-20% by weight of one or more diols having having a molecular weight not exceeding 200 and of which one or both hydroxy groups may be alkylated or acylated.  The alcohol component may be ethyl or isopropyl alcohol and specified diols include glycol, diethylene glycol, 1,2-propylene glycol, 1,3 or 2,3-butanediol, ethyl-, propyl- or butylglycol or diglycol, glycol monoacetate or methylethyl-, propyl- or buty-glycol monoacetate and 3-methyl- 2,4-pentanediol.  The composition preferably also contains a halohydrocarbon propellant and is enclosed in an aerosol spray container.  Surface active agents and perfumes may also be present.