anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is an outpatient Phase 1 clinical trial investigating the effect of naloxone precipitated withdrawal on delay discounting. Eligible participants will undergo two experimental sessions presented in random order. One session will involve the measurement of delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo (normal saline) and the other will have the exact same procedures performed after double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid withdrawal measures assessed at baseline and 15 minute intervals after injections. The participant should be back to baseline and free of withdrawal by the end of the study session. Sessions will occur at least 48 hours apart.
Multi-organ hypersensitivity reactions have occurred in close temporal association (median time to detection 13 days: range 4-60) to the initiation of oxcarbazepine therapy in adult and pediatric patients. Although there have been a limited number of reports, many of these cases resulted in hospitalization and some were considered life threatening. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. These may include hematologic and lymphatic (e.g., eosinophilia, thrombocytopenia, lymphadenopathy, leukopenia, neutropenia, splenomegaly), hepatobiliary (e.g., hepatitis, liver function test abnormalities), renal (e.g., proteinuria, nephritis, oliguria, renal failure), muscles and joints (e.g., joint swelling, myalgia, arthralgia, asthenia), nervous system (e.g., hepatic encephalopathy), respiratory (e.g., dyspnea, pulmonary edema, asthma, bronchospasm, interstitial lung disease), hepatorenal syndrome, pruritus, and angioedema. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, oxcarbazepine should be discontinued and an alternative treatment started. Although there are no case reports to indicate cross sensitivity with other drugs that produce this syndrome, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility [see Warnings and Precautions (5.3)].
Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates are a public health concern as they can cause severe hospital-acquired infections that are difficult to treat. It has recently been shown that CP-Kp can take up virulence factors from hypervirulent K. pneumoniae lineages. In this study, 109 clinical CP-Kp isolates from the University Hospital Cologne were examined for the presence of acquired virulence factors using whole-genome sequencing and phenotypic tests, and results were linked to clinical data. The virulence factor iuc was present in 18/109 of the CP-Kp isolates. Other acquired virulence factors, such as ybt, cbt, iro, rmpA/rmpA2, peg-344, and hypervirulence-associated capsule types were detected in various combinations among these isolates. The iuc-positive isolates produced OXA-232 (n = 7), OXA-48 (n = 6), OXA-48+NDM (n = 3), NDM, and KPC (each n = 1), and 7/18 isolates were resistant to ceftazidime-avibactam, colistin, and/or cefiderocol. Four isolates carried hybrid plasmids that harbored acquired virulence factors alongside the carbapenemase genes blaNDM-1/5 or blaOXA-48. In 15/18 patients, iuc-positive CP-Kp were isolated from a clinically manifest infection site. Among these, four patients had osteomyelitis, and four patients died from pneumonia with OXA-232-producing ST231 isolates, three of them as part of an outbreak. In conclusion, acquired virulence factors are frequently detected in various combinations in carbapenemase-producing K. pneumoniae isolates in Germany, warranting continuous monitoring of infections caused by these strains.
FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to novel derivatives of dibenzoxazepine or dibenzodioxepine of the formula (I)   where R 1  and R 2  means independently hydrogen atom, unsubstituted lower alkyl or lower alkyl substituted with lower alkoxy-group or lower alkylthio-group or acyl-group that can be unsubstituted or substituted with one or some substituents taken among the group including lower alkyl, lower alkyl substituted with halogen atom or lower alkoxy-group; X means CO or CHOH; Y means CO or CH 2 ; Z means O or NH, and their epimers and enantiomers or physiologically acceptable salts. Also, invention relates to antitumor pharmaceutical composition containing effective amount of compound of the formula (I). Compounds can be used as anticancer drugs. EFFECT: new compounds indicated above, valuable anticancer properties. 35 cl, 3 tbl
A prospective follow-up was arranged for the 18 pregnant women with excessive iodine status. History of iodine exposure (including hysterosalpingography (HSG) using an oil-soluble iodinated contrast medium, examination by computed tomography scan with contrast, administration of amiodarone, history of receiving radioiodine therapy, etc.) was collected from all participants. Evaluation of dietary iodine intake was performed through a 72-hour dietary recall.The serum iodine concentration (SIC) and urinary iodine concentration (UIC) were monitored continuously in the whole course of pregnancy. All subjects with excessive iodine load were recommended by nutritionists to have their dietary iodine intake restricted, and resume iodine-containing supplements and foods until the UIC\<250 μg/L and SIC≤90 μg/L. After delivery, maternal colostrum iodine concentration and neonatal iodine status (including neonatal UIC, condition of congenital hypothyroidism screening tests, and thyroid physical examination) were also assessed.
Concurrent use of azelastine hydrochloride nasal solution with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur. 

Cimetidine (400 mg twice daily) increased the mean Cmax and AUC of orally administered azelastine hydrochloride (4 mg twice daily) by approximately 65%. Ranitidine hydrochloride (150 mg twice daily) had no effect on azelastine pharmacokinetics. 

Interaction studies investigating the cardiac effects, as measured by the corrected QT interval (QTc), of concomitantly administered oral azelastine hydrochloride and erythromycin or ketoconazole were conducted. Oral erythromycin (500 mg three times daily for seven days) had no effect on azelastine pharmacokinetics or QTc based on analyses of serial electrocardiograms. Ketoconazole (200 mg twice daily for seven days) interfered with the measurement of azelastine plasma concentrations; however, no effects on QTc were observed. 

No significant pharmacokinetic interaction was observed with the coadministration of an oral 4 mg dose of azelastine hydrochloride twice daily and theophylline 300 mg or 400 mg twice daily.
BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities.
EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated β-galactosidase (SA-β-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies.
KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3.
CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.
The intestine constantly encounters and adapts to the external environment shaped by diverse dietary nutrients. However, whether and how gut adaptability to dietary challenges is compromised in ulcerative colitis is incompletely understood. Here, we show that a transient high-fat diet exacerbates colitis owing to inflammation-compromised bile acid tolerance. Mechanistically, excessive tumor necrosis factor (TNF) produced at the onset of colitis interferes with bile-acid detoxification through the receptor-interacting serine/threonine-protein kinase 1/extracellular signal-regulated kinase pathway in intestinal epithelial cells, leading to bile acid overload in the endoplasmic reticulum and consequent apoptosis. In line with the synergy of bile acids and TNF in promoting gut epithelial damage, high intestinal bile acids correlate with poor infliximab response, and bile acid clearance improves infliximab efficacy in experimental colitis. This study identifies bile acids as an "opportunistic pathogenic factor" in the gut that would represent a promising target and stratification criterion for ulcerative colitis prevention/therapy.
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
PURPOSE: To evaluate the clinical outcomes of the use of tibiotalocalcaneal nail for the treatment of complex distal tibia and ankle fractures in elderly people, in a major trauma centre.
METHODS: Elderly patients (age > 65) with distal tibia or ankle fractures that underwent stabilization with a tibiotalocalcaneal nail were eligible to participate. Exclusion criteria were patients that died or were lost to follow-up and cases in which the nail was used in a chronic setting, such as malunion and non-union. Main parameters evaluated were fracture union, complications and functional outcomes. The functional outcome was assessed using the Olerud-Molander Ankle Score (OMAS). The minimum follow-up was 12 months.
RESULTS: Thirty-two consecutive patients (12 males) with a mean age of 80.2 years (range 66-98) met the inclusion criteria and formed the basis of this study. Fracture union was achieved in 93.8% of the cases at a mean time of 3.9 months (range 2-8). Two patients developed surgical site infections and underwent reoperation before union. The overall complication rate was 25.1%, while the respective reintervention rate was 18.8%. In terms of functional outcomes, the mean OMAS score was 45, ranging from 20 to 70.
CONCLUSION: Tibiotalocalcaneal nailing can be considered as an acceptable less invasive option with good functional outcomes for the treatment of complex distal tibia and ankle fractures in frail patients with problematic local soft tissues.
Fifty-one 18-22-year-old Ugandans took part in asynchronous online discussions about sexual decision-making. To increase generalizability and variability of experience, youth were recruited across the country using social media advertising. Participants were stratified into 8 groups by sex and sexual experience (e.g., women who had not had sex). Participants were asked questions such as, "What role do you think [men/women] play in deciding when a couple is going to play sex?" Several themes emerged. Both young men and women articulated social pressures to be abstinent, particularly to avoid STIs and pregnancy moreso than saving oneself for marriage. That said, women noted pressures to be seen as "pure". There also were pressures to have sex: Men were expected to have sex to demonstrate their virility. Women were expected to have sex if they accepted gifts or other commodities from their partners. It seemed that the specter of HIV and other STIs, as well as unwanted pregnancy, served to mitigate these expectations however, resulting in self-efficacy to use condoms among both men and women. Nonetheless, both men and women acknowledged that it could be hard for women to negotiate condoms. Implications for HIV prevention are discussed.
BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere.
METHODS: In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp).
RESULTS: The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp.
DISCUSSION: Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.
The invention belongs to the field of traditional Chinese medicine and discloses a Caulis dendronii healthcare product having efficacy of improving immunity. The Caulis dendronii healthcare product contains 20 parts of Caulis dendronii, 18 parts of Begonia fimbristipula, 20 parts of medical angiopteris rhizome, 15 parts of root of Vitex negundo, 20 parts of fine-stemmed dendrobium, 20 parts of Desmodium caudatum and 6 parts of Radix glycyrrhizae. Dosage forms are granules, tablets and capsules. The invention further discloses a preparation method. The preparation method includes: adding water for decocting, concentrating, performing alcohol precipitation, spraying for drying, smashing obtained granules into dry extract powder, adding auxiliary materials, and obtaining the healthcare product. The invention further discloses application of the method in preparing the healthcare product having efficacy of improving immunity.
BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying brain injury resulting from intracerebral hemorrhage (ICH) remain incompletely elucidated, and efficacious therapeutic interventions to enhance the prognosis of ICH patients are currently lacking. Previous research indicates that MicroRNA-7 (miR-7) can suppress the expression of Nod-like receptor protein 3 (NLRP3), thereby modulating neuroinflammation in Parkinson's disease pathogenesis. However, the potential regulatory effects miR-7 on NLRP3 inflammasome after ICH are yet to be established. This study aims to ascertain whether miR-7 mitigates secondary brain injury following experimental ICH by inhibiting NLRP3 and to investigate the underlying mechanisms.
METHODS: An ICH model was established by stereotaxically injecting 100 μL of autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. Subsequently, these rats were allocated into three groups: sham, ICH + Vehicle, and ICH + miR-7, each comprising 18 animals. Twelve hours post-modeling, rats received intraventricular injections of 10 μL physiological saline, 10 μL phosphate, and 10 μL phosphate-buffered saline solution containing 0.5 nmol of miR-7 mimics, respectively. Neurological function was assessed on day three post-modeling, followed by euthanasia for brain tissue collection. Brain water content was determined using the dry-wet weight method. The expression of inflammatory cytokines in cerebral tissues surrounding the hematoma was analyzed through immunohistochemistry and Western blot assays. These cytokines were re-evaluated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Moreover, bioinformatics tools were employed to predict miR-7's binding to NLRP3. A wild-type luciferase reporter gene vector and a corresponding mutant vector were constructed, followed by transfection of miR-7 mimics into HEK293T cells to assess luciferase activity.
RESULTS: Our study demonstrates that the administration of miR-7 mimics markedly reduced neurological function scores and attenuated brain edema in rats following ICH. A significant upregulation of NLRP3 expression in microglia/macrophage adjacent to the hematoma was observed, substantially reduced after the treatment with miR-7 mimics. Furthermore, this intervention ameliorated neurodegenerative changes and effectively decreased the protein and mRNA levels of pro-inflammatory cytokines, namely TNF-α, IL-1β, IL-6, and Caspase1, in the cerebral tissues proximate to the hematomas. In addition, miR-7 mimics distinctly inhibited the luciferase activity associated with the wild-type reporter gene, an effect not mirrored in its mutant variant.
CONCLUSIONS: The miR-7 suppressed NLRP3 expression in microglia/macrophage to reduce the production of inflammatory cytokines, leading to conducting certain neuroprotection post-ICH in rats.
The development of nonalcoholic fatty liver disease (NAFLD) may worsen due to chronic stress or prolonged use of glucocorticoids. Glycerol-3-phosphate acyltransferase 3 (GPAT3), has a function in obesity and serves as a key rate-limiting enzyme that regulates triglyceride synthesis. However, the precise impact of GPAT3 on corticosterone (CORT)-induced NAFLD and its underlying molecular mechanism remain unclear. For our in vivo experiments, we utilized male and female mice that were GPAT3-/- and wild type (WT) and treated them with CORT for a duration of 4 weeks. In our in vitro experiments, we transfected AML12 cells with GPAT3 siRNA and subsequently treated them with CORT. Under CORT-treated conditions, the absence of GPAT3 greatly improved obesity and hepatic steatosis while enhancing the expression of genes involved in fatty acid oxidation, as evidenced by our findings. In addition, the deletion of GPAT3 significantly inhibited the production of reactive oxygen species (ROS), increased the expression of antioxidant genes, and recovered the mitochondrial membrane potential in AML12 cells treated with CORT. In terms of mechanism, the absence of GPAT3 encouraged the activation of the glycogen synthase kinase 3β (GSK3β)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which served as a defense mechanism against liver fat accumulation and oxidative stress. Furthermore, GPAT3 expression was directly controlled at the transcriptional level by the glucocorticoid receptor (GR). Collectively, our findings suggest that GPAT3 deletion significantly alleviated hepatic steatosis and oxidative stress through promoting GSK3β/Nrf2 signaling pathways.
Laparoscopic appendectomy is gradually evolving as the 'gold standard' in the treatment of acute appendicitis, especially in the obese, elderly, and in cases where the diagnosis is uncertain . There are clear benefits with the laparoscopic approach in terms of decreased pain and faster recovery than the open approach . However, disadvantages like a higher incidence of intra-abdominal collection, longer operating time, and higher costs have been documented. These may be dependent on the technique of appendicular stump closure. Therefore, the technique for appendiceal stump closure is crucial in laparoscopic appendectomy.

Laparoscopic appendectomy was first described by Semm in 1983 and is currently preferred approach for an appendectomy for many surgeons. Numerous methods of stump closure have been used, like intracorporeal suturing of the stump endoloop application, endostapler application LigaSure customized titanium clip application, and, more recently, using nonabsorbable plastic clips . Many of these techniques are either time consuming or expensive, or not available universally.
<P>PROBLEM TO BE SOLVED: To efficiently extract a large amount of an active ingredient from Pachyma hoelen Rumph. which is fungi abundantly containing polysaccharides having an antitumor activity.  <P>SOLUTION: A method for extracting the antitumor active substance of a crude drug comprises using the Pachyma hoelen Rumph. which is the fungi abundantly containing the polysaccharides having the antitumor activity. The method is carried out by decocting the fungi together with exodermis and decocting the fungi for 5-6 h using water at a temperature of at least ≥95°C. β-Glucan which is the active ingredient contained therein and trace constituents contained in the exodermis thereof can well be extracted by the method for extraction.  <P>COPYRIGHT: (C)2008,JPO&INPIT
A topical foam pharmaceutical composition for rectal administration comprising rifaximin in the form of nanosized particles is described. Also described is a method of making the composition and the use of the composition to as a medicament. A topical foam pharmaceutical composition for rectal administration comprising rifaximin in the form of nanosized particles is described. Also described is a method of making the composition and the use of the composition to as a medicament. Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.