anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PCT No. PCT/DK87/00104 Sec. 371 Date Apr. 26, 1988 Sec. 102(e) Date Apr. 26, 1988 PCT Filed Aug. 25, 1987 PCT Pub. No. WO88/01615 PCT Pub. Date Mar. 10, 1988.   <IMAGE> (I)  Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R-COO-represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
ETHNOPHARMACOLOGICAL RELEVANCE: Compound Jixuecao Decoction (CJD) is a traditional Chinese herbal medicine prescribed in China to treat chronic renal failure (CRF). Previous studies have shown that CJD affects cell apoptosis and proliferation. However, the mechanism of its renal protective action has not been characterized.
AIM OF THE STUDY: To explore the mechanism(s) underlying the effect of CJD on endoplasmic reticulum stress (ERS) and apoptosis in the treatment of CRF using network pharmacology, molecular docking, molecular dynamics simulations, and in vivo studies.
MATERIALS AND METHODS: The compounds comprising CJD were extracted from the Traditional Chinese Medicine Systems Pharmacology Database. A Swiss target prediction database and similarity integration approach were employed to identify potential targets of these components. The GeneCards and DisGeNET databases were used to identify targets associated with CRF, apoptosis, and ERS. The STRING database was employed to analyze the protein-protein interactions (PPIs) associated with drug-disease crossover. A chemical composition-shared target network was established, and critical pathways were identified through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The Protein Data Bank database was used to search key proteins, while molecular docking and dynamics simulations were performed between the top four CJD active ingredients and proteins involved in apoptosis and ERS in CRF. Subsequent in vivo studies using a 5/6 nephrectomy rat model of CRF were performed to verify the findings.
RESULTS: The 80 compounds identified in CJD yielded 875 target genes, of which 216 were potentially related to CRF. PPI network analysis revealed key targets via topology filtering. Enrichment analysis, molecular docking, and molecular dynamics simulation results suggested that CJD primarily targets mitofusin-2 (MFN2), B-cell lymphoma-2 (BCL2), BAX, protein kinase RNA-like ER kinase (PERK), and C/EBP homologous protein (CHOP) during CRF treatment. In vivo, CJD significantly increased the abundance of MFN2, BCL2, and significantly reduced the abundance of BAX, PERK, CHOP proteins in kidney tissues, indicating that CJD could improve apoptosis and ERS in CRF rats.
CONCLUSIONS: This study provides evidence that CJD effectively delays CFR through modulation of the MFN2 and PERK-eIF2α-ATF4-CHOP signaling pathways.
Recent advances in haptic technology could allow haptic hearing aids, which convert audio to tactile stimulation, to become viable for supporting people with hearing loss. A tactile vocoder strategy for audio-to-tactile conversion, which exploits these advances, has recently shown significant promise. In this strategy, the amplitude envelope is extracted from several audio frequency bands and used to modulate the amplitude of a set of vibro-tactile tones. The vocoder strategy allows good consonant discrimination, but vowel discrimination is poor and the strategy is susceptible to background noise. In the current study, we assessed whether multi-band amplitude envelope expansion can effectively enhance critical vowel features, such as formants, and improve speech extraction from noise. In 32 participants with normal touch perception, tactile-only phoneme discrimination with and without envelope expansion was assessed both in quiet and in background noise. Envelope expansion improved performance in quiet by 10.3% for vowels and by 5.9% for consonants. In noise, envelope expansion improved overall phoneme discrimination by 9.6%, with no difference in benefit between consonants and vowels. The tactile vocoder with envelope expansion can be deployed in real-time on a compact device and could substantially improve clinical outcomes for a new generation of haptic hearing aids.
OBJECTIVE: To describe the prevalence of urinary incontinence (UI) in para athletes in Brazil.
METHODS: This is a cross-sectional study with Brazilian para athletes with physical impairments from all para sports. The data from 86 participants of both sexes (60 males and 26 females) were collected through an online survey that gathered sociodemographic data and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, from March to July 2023.
RESULTS: The prevalence of UI was 45.3% (n=39), with the average impact on quality of life scored at 6.1±3.5 on a scale of 0-10. Most para athletes reported moderate (43.5%) or severe (38.4%) symptoms. The most common type was mixed UI (46.1%), with an average of 3±1.9 episodes of urinary loss per athlete in the last 4 weeks. Adjusted Poisson regression (controlling for sex, age and level of competition) revealed that para athletes with orthopaedic impairments had a 58% lower prevalence of UI (prevalence ratio=0.42; 95% CI 0.24, 0.83) compared with those with neurological impairments. Furthermore, ordinal regression indicated that para athletes with neurological impairments were 147% more likely to experience a progression from 'severe' to 'very severe' UI (OR=2.47; 95% CI 1.59, 3.93).
CONCLUSIONS: UI is highly prevalent among para athletes, particularly those with neurological impairments, underscoring the need for specialised genitourinary healthcare and the need for further treatment and monitoring of the condition. There is a critical need to raise awareness among coaches, healthcare providers and the athletes themselves about UI and its impact to foster the comprehensive well-being of these athletes.
This is a prospective, paired study. Study subjects who are scheduled to undergo EUS at Mayo Clinic will be identified through Epic. Chart review will be performed including review of prior imaging, medical history, and laboratory results as available in Epic to determine study eligibility. Subjects without history of chronic liver disease (screened by low FIB-4 score) and those with known advanced fibrosis/cirrhosis will be eligible for the study. Eligible study subjects will then be contacted either before, or at the time of their endoscopy procedure to discuss study participation. All subjects will then receive standard clinical care based on the indication for the EUS procedure. During the EUS procedure, study subjects with undergo shear wave measurements obtained in a non-invasive manner as part of the endosonographic evaluation of the liver. 10 measurements (including shear wave velocity (Vs), elastic modulus (E)) will be obtained for point SWE (pSWE). Measurements will be obtained from both left and right lobes of liver unless technically infeasible to do so. Study subjects will then undergo a paired MR elastography (same day or at later date) after completion of EUS and only if consistent and reliable shear wave measurements were obtained (e.g., VsN \> 70%(reliability index of each measurement expressed in percentages), IQR/M (interquartile range/ Median) is \<15% for Vs and \<30% for E). Enrolled study subjects who had undergone a previous MRE (within 6 months of enrollment) would be eligible for the study, without the need to undergo further research MRE. After completion of MR elastography, the subjects will then continue through their routine clinical care and will not be followed up by research staff. The expected duration of subject participation is anticipated to begin at the time of study enrollment and terminate after completion of MR elastography. There will be no additional follow up.
Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks).
The study will be performed in three cohorts with different dose levels. Eligible patients will receive one cycle of 90Y-PTT, which will be administered intravenously.
FIELD: medicine. ^ SUBSTANCE: intraoperationally introduced is fluoruracyl in dose 1000 mg/m and leukovorine in dose 100 mg/m after incubation with 100 ml of ozonised 400 mcg/l of autoblood intravenously. Oxaliplatin in dose 100 mg/m2 with 50 ml of ozonised 1000 mcg/l physiological solution is introduced into left gastric artery. Exposition of medications is 30 min. Gastrectomy is performed. After 7 days blood is sampled from patient in amount 100 ml in sterile vial with glugicir. Blood is bubbled. Concentration of ozone in ozone-oxygen mixture is 400 mcg/l. 100 mg/m2 of oxaliplatine are added and re-infused to patient intravenously, in drops. Next day 1000 mg/l of fluoruracyl and 100 mg/m2 of leukovorine are introduced successively intravenously, in drops with 100 ml of ozonised 400 mcg physiological solution. Treatment is repeated two times more with 3 week interval. ^ EFFECT: method makes it possible to prolong remission terms. ^ 1 ex
Neuromuscular electrical stimulation (NMES) and Eccentric Exercise (ECC). Patients randomized to the NMES+ECC group will first receive NMES for 2x/week for 8 weeks, beginning at the first post-operative visit. Beginning at 9 weeks after anterior cruciate ligament reconstruction (ACLR) patients will begin to receive eccentric exercise 2x/week for an additional 8 weeks. For NMES, patients will have electrical stimulation delivered to their quadriceps. Fifteen isometric actions lasting 10 seconds each will be elicited during each session. For eccentric exercise, patients will train for 4 sets of 10 repetitions. This group will also receive standard of care ACL rehabilitation alongside the study interventions.
PURPOSE:To prepare the titled compound useful as a synthetic intermediate of a spergualin-mimic compound useful as a carcinostatic agent, by the selective oxidative scission of the corresponding C-C bond of a compound such as N-seryl- spermidine, etc. CONSTITUTION:The objective compound of formula II can be prepared by the oxidative scission of the corresponding C-C bond of the compound of formula I (R<1> is OH or NH2 provided that all R<1> are not NH2 at the same time; R<2> is H or alkyl, carboxyl, etc. which may have substituent group). The compound of formula I gives the objective compound by the oxidative scission irrespective of the substituent group of R<2>. For example, N-seryl-spermidine of formula IIIwherein R<1> is NH2 and OH and R<2> is H can be prepared by reacting the compound of formula I with periodic acid as the oxidative scission reagent usually in an aqueous solution. Other examples of the compound of formula I usable as a substrate is the compound of formula IV and formula V.
The safety and efficacy of midazolam for sedation/anxiolysis/amnesia following single dose intramuscular administration, intravenously by intermittent injections and continuous infusion have been established in pediatric and neonatal patients. For specific safety monitoring and dosage guidelines see Boxed WARNING, CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, OVERDOSAGE and DOSAGE AND ADMINISTRATION sections. UNLIKE ADULT PATIENTS, PEDIATRIC PATIENTS GENERALLY RECEIVE INCREMENTS OF MIDAZOLAM ON A MG/KG BASIS. As a group, pediatric patients generally require higher dosages of midazolam (mg/kg) than do adults. Younger (less than six years) pediatric patients may require higher dosages (mg/kg) than older pediatric patients, and may require closer monitoring. In obese PEDIATRIC PATIENTS, the dose should be calculated based on ideal body weight. When midazolam is given in conjunction with opioids or other sedatives, the potential for respiratory depression, airway obstruction, or hypoventilation is increased. The health care practitioner who uses this medication in pediatric patients should be aware of and follow accepted professional guidelines for pediatric sedation appropriate to their situation.

Midazolam should not be administered by rapid injection in the neonatal population. Severe hypotension and seizures have been reported following rapid IV administration, particularly, with concomitant use of fentanyl.
The first study is a two-group randomized controlled trial in which 6,000 male and female probationers and parolees in Baltimore City, Maryland and Providence, Rhode Island will be randomly assigned to one of two treatment conditions: 1) On-site rapid testing conducted by research staff co-located for the purposes of this study at the probation/parole office; or 2) Off-site referral for rapid HIV testing at a community health center or HIV testing clinic. Inclusion criteria will be: 1) Adult probationer/parolee; 2) not known to be HIV positive, and 3) resident of greater Baltimore or Providence throughout the study period. Exclusion criteria will be: 1) unable to give informed consent. The second study is a randomized trial, whereby all individuals identified at community corrections with HIV will be offered enrollment in a one-year intervention study to examine the ability to improve linkage into HIV care. Participants will be randomized to receive one of two conditions: 1) Project Bridge for one year, or 2) Treatment as Usual-referral to standard level of care. Moreover, those randomized to TAU will be given an opportunity to "crossover" to PB if they have failed to engage in treatment during the first three months. The rationale for choosing the two cities of Baltimore, MD and Providence, RI is due to the historically high rates of heroin addiction that is associated with multiple HIV-related risk behaviors in these two cities and a high likelihood of being on probation and/or parole. Furthermore, Maryland ranks 10th and Rhode Island ranks 4th in the nation in the number of probationers per 100,000 adult residents.
A substantially pure, hemagglutinin-free composition of trichosanthin, and a method of producing the composition is disclosed. A plant extract from Trichosanthes kirilowii is contacted with an anionic exchange resin to remove contaminating hemagglutinins, and trichosanthin is further purified from the extract by cation exchange chromatography to a purity of greater than 95 %. Also disclosed is a stable trichosanthin composition suitable for parenteral injection and a method of producing the stable composition. The stable composition is formed by adding a non-ionic surfactant and sucrose, to an aqueous solution of purified trichosanthin. This composition can be stored in aqueous form for several days at between 2-8°C without significant protein precipitation. Alternatively, the stable composition can be stored in lyophilized form, and reconstituted with substantially complete resolubilization of the protein.
Infertility

RECORLEV may lower testosterone levels [see Warnings and Precautions ( 5.5)] and impair male and female fertility. Ketoconazole tablets (containing equal parts levoketoconazole and dextroketoconazole in a racemic mixture) have been demonstrated to lower serum testosterone in humans. Once therapy with ketoconazole tablets was discontinued, serum testosterone levels returned to baseline values. Testosterone levels are impaired with ketoconazole doses of 800 mg per day and abolished by 1600 mg per day. Clinical manifestations of decreased testosterone concentrations may include gynecomastia, impotence and oligospermia. In rat fertility studies, oral ketoconazole administered at doses equivalent to the MRHD of levoketoconazole by BSA during premating to implantation caused impaired fertility in male and female rats. In dog fertility studies, levoketoconazole targeted the reproductive tissues of male dogs in a dose-dependent manner with associated effects on spermatogenesis and maturation of spermatozoa. The effect was reversible upon discontinuation of treatment [see Nonclinical Toxicology ( 13.1)] .
A method of treating a mammalian patient suffering from or prone to a condition characterised by late phase allergic reactions, airway hyperresponsiveness or inflammatory reactions, e.g., asthma, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, inflammatory bowel disease or rheumatoid arthritis.  The method comprises the administration of an oral, parenteral, intrabronchial, topical, intranasal or intraocular pharmaceutical composition containing in each dose about 0.005 to about 1.0 mg per kilogram of patient body weight of ultra-low molecular weight heparins (ULMWH) or other sulphated polysaccharides having average molecular weights of about 1,000-3,000 daltons.  Suitable inhalant and other pharmaceutical compositions for use in this treatment method are also disclosed. Depicted is a graph illustrating the effect of pretreatment with inhaled ULMWH CY-222 (avg. mol. wt. 2,355 daltons) at 1.0 mg/kg on antigen-induced bronchoconstriction in dual responder allergic sheep.  Data are shown as antigen induced mean +/- SE% change in SR, in a group of animals exposed to antigen, first with no drug treatment and again several days later after pretreatment with CY-222. * = Significantly different from control (P < .05)
Pediatric bipolar disorder (BD) is difficult to distinguish from other psychiatric disorders, a challenge which can result in delayed or incorrect interventions. Using neuroimaging we aimed to identify neural measures differentiating a rarified sample of inpatient adolescents with BD from other inpatient psychopathology (OP) and healthy adolescents (HC) during a reward task. We hypothesized reduced subcortical and elevated cortical activation in BD relative to other groups, and that these markers will be related to self-reported mania scores. We examined inpatient adolescents with diagnosis of BD-I/II (n = 29), OP (n = 43), and HC (n = 20) from the Inpatient Child and Adolescent Bipolar Spectrum Imaging study. Inpatient adolescents with BD showed reduced activity in right thalamus, left thalamus, and left amygdala, relative to inpatient adolescents with OP and HC. This reduced neural function explained 21% of the variance in past month and 23% of the variance in lifetime mania scores. Lower activity in regions associated with the reward network, during reward processing, differentiates BD from OP in inpatient adolescents and explains >20% of the variance in mania scores. These findings highlight potential targets to aid earlier identification of, and guide new treatment developments for, pediatric BD.
Subjects will receive single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
This is a pilot study in subjects with a histologically proven diagnosis of glioblastoma (GB) who have completed chemoradiation and now have new contrast enhancing lesions or lesions showing increased enhancement ( 25% increase) who are recommended for a clinical surgical resection. Subjects may participate in this study if they are at least 18 years of age, most participants will be receiving care at the clinical practices of the University of Pennsylvania. Subjects who come to the University of Pennsylvania for diagnosis and/or treatment of GB and who meet the study inclusion criteria may be approached by study personnel for recruitment into this study. Subjects will be approached about study participation regardless of race or ethnic background. Investigators anticipate enrolling up to 30 participants. Subjects who consent but do not complete the study imaging will be considered not evaluable and will be replaced. Accrual will likely occur over approximately 1-2 years. After undergoing screening assessments and verifying eligibility for study participation subjects will undergo a research 18FFluciclovine PET/CT scan of the brain and a clinical brain MRI with and without gadolinium contrast, all baseline imaging will be done prior to (within 1 week) of the surgical procedure. The PET-CT and MRI can be performed in any order.
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as the presence of a DDI would translate into reduced or abolished antiplatelet effects exposing these acute patients to an increased thrombotic risk. Despite the available evidence suggesting a lack of DDI with the use of ticagrelor in cangrelor treated patients, most data derive from studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. To date, there is no data to fully rule out a DDI when ticagrelor is given prior to starting cangrelor infusion. The need for such investigation is underscored by the relatively high prevalence of pretreatment with ticagrelor in acute settings. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a DDI when ticagrelor is administered prior to cangrelor infusion.