anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is a 2-group parallel (high-grade astrocytoma, diffuse pontine tumor), single stage study investigating cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in pediatric and young adult patients. Optional exploratory components of the study include (1) correlation of tumor molecular markers with outcome, (2) CSF proteomics, and (3) assay of serum cytokine levels in patients who develop a cetuximab-associated rash.
Spasmodic dysphonia (SD), or laryngeal dystonia, is a chronic debilitating condition that selectively affects speech production due to involuntary spasms in the laryngeal muscles. SD often extends beyond the impairment of vocal communication causing significant occupational disability and life-long social isolation. SD becomes even more incapacitating when it is associated with dystonic voice tremor (VT), which is present in about 1/3 of SD patients and is characterized by the inability to sustain a vowel for more than a few seconds. Current treatment of these disorders is limited to the temporary management of voice symptoms with repeated injections of botulinum toxin into the laryngeal muscles. These injections, however, are not fully effective in all SD patients and even less so in combined SD and VT cases. There is, therefore, a critical need to identify alternative therapeutic options that specifically target the pathophysiology of these disorders. On the other hand, the design and the use of such novel therapeutic approaches will be largely unattainable if their central mechanisms of action remain unknown. The objective of this study is to elucidate the primary determinants of clinical response to a novel oral medication, sodium oxybate (Xyrem®), in alcohol-responsive SD and VT patients. Using a comprehensive approach of clinico-behavioral testing, neuroimaging and pharmacogenetics, we aim to determine the clinical response of SD and VT symptoms to sodium oxybate and identify the primary markers of its clinical benefits. This study will use a controlled experimental design that focuses on detailed characterization of primary effects of a novel oral medication, sodium oxybate, for treatment of SD and VT symptoms.
Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.
Parent peer navigation (PPN), provided by other caregivers who have lived experience raising a youth with mental health conditions, holds promise as a service that can aid in improving both youth and caregiver outcomes by overcoming system- and individual-level barriers to care. This proposed study will support initial testing of a research- and theory- based Parent Peer Navigation (PPN) model created by one of the nation's leading advocacy organizations for caregivers of children and youth with mental health challenges, the federally funded Family-Run Executive Directors Leadership Association. This model, called the National Parent Peer Support Practice Model (Practice Model) has an associated training program and aims to effectively engage parents/caregivers in necessary treatment for their children by helping them connect with assessment, treatment and community-based resources and prepare them to independently navigate the child serving system, community-based resources, and ongoing opportunities for support once the PPN provider is no longer involved. The Practice Model incorporates five theory- and research-based components of support: (1) information/educational, (2) instructional/skills development; (3) emotional/ affirming, (4) instrumental; and (5) advocacy. The study will focus on children in early stages of impairment as a result of mental health challenges for which prevention of further disability is possible. It will take advantage of implementation of the Practice Model through two non-profit family-run organizations (FROs) and will occur in three phases, beginning with preparatory work to develop recruitment strategies in collaboration with local schools, formalize implementation outcomes (acceptability, appropriateness, feasibility, fidelity) and other measures followed by a Feasibility Study to finalize recruitment, procedures and measurement frames. Finally, in Phase 3, the investigators will conduct a cluster randomized trial to provide a preliminary test of the impact of the Practice Model on key caregiver and child outcomes. Children who are experiencing mental health challenges but have not had exposure to formal mental health services will be identified by collaborating schools and FROs/FSOs and referred for family support. Consenting families will be randomly assigned to a treatment group who will receive PPN services based on the Practice Model from participating FROs, or a comparison group who will be referred to a Family Support Organization which provide other types of resources (e.g., referrals, information). The investigators predict that youth and parents receiving PPN will show significantly greater rates of access, engagement and retention in services as compared to the comparison group. The investigators also predict that at 6 months following PPN onset, children in the treatment group will exhibit improved social/emotional functioning and that parents in the treatment group will exhibit increased empowerment and decreased parenting stress, as compared to those in the comparison group.
FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to thenylazolylalkoxyethaneamines of the formula (I)   wherein R1 means hydrogen atom, halogen atom or lower alkyl radical; R2, R3 and R4 mean independently hydrogen atom or lower alkyl radical; Az means nitrogen-containing aromatic N-methyl-substituted five-membered heterocycle comprising from one to three nitrogen atoms eliciting analgetic activity. Invention describes also methods for preparing compounds of the formula (I), intermediate compound used in synthesis, method for their preparing and pharmaceutical composition. Compounds can be used as agents with analgetic activity. EFFECT: improved preparing methods, valuable medicinal property of compounds. 15 cl, 4 tbl, 12 ex
The invention comprises compounds of the formula <FORM:0875602/IV (b)/1> (wherein A represents a straignt or branched chain saturated C2-C4 alkylene group in which at least two carbon atoms separate the nitrogen atoms to which A is attached, R represents a hydrogen atom or an acyl or a carbomoyl group of the formula -CO-NR1R2 where R1 and R2 are the same or different and represent hydrogen atoms or alkyl groups or, together with the adjacent nitrogen atom, represent a mononuclear heterocyclic ring, and n is 0, 1 or 2) and acid addition and quaternary ammonium salts thereof, and the preparation thereof by reacting a piperidine of the formula <FORM:0875602/IV (b)/2> with a compound of the formula <FORM:0875602/IV (b)/3> (wherein X represents a reactive ester residue) or, where R represents an acyl or carbomoyl group, by acylating or carbomoylating the appropriate hydroxy compound and, if desired, converting the products of any of these processes into their acid addition or quaternary ammonium salts.  The invention includes pharmaceutical compositions containing the products (see Group VI).  The compounds may also be prepared by reacting a compound of the formula <FORM:0875602/IV (b)/4> with iminodibenzyl.  The products are psychotonics, anti-histaminics and anti-emetics.ALSO:Pharmaceutical compositions containing compounds of the formula <FORM:0875602/VI/1> p  (wherein A represents a straight or branched chain saturated C2-4 alkylene group in which at least two carbon atoms separate the nitrogen atoms to which A is attached, R represents a hydrogen atom or an acyl or a carbamoyl group of the formula -CO-NR1R2, where R1 and R2 are the same or different and represent hydrogen atoms or alkyl groups or, together with the adjacent nitrogen atom, represent a mononuclear heterocyclic ring, and n is 0, 1 or 2) or acid addition or quaternary ammonium salts thereof, with a diluent, may be in forms suitable for oral and parenteral administration e.g. tablets, pills, dispersible powders, granules, capsules, solutions, emulsions, suspensions, syrups and elixirs.  Acid addition salts specified include hydrohalides, phosphates, nitrates, sulphates, maleates, fumarates, citrates, tartrates, methanesulphonates and ethanedisulphonates.  Quaternary ammonium salts include those with methyl or ethyl iodide, chloride or bromide or allyl or benzyl chloride or bromide or toluene-p-sulphonate.
The invention provides ozagrel fat emulsion injection and a preparation method thereof, belonging to the technical field of ozagrel injection. The ozagrel injection provided by the invention takes water as a solvent, and is prepared from the following raw materials in concentration: 1-10 g/kg of ozagrel; 10-50 g/kg of egg yolk lecithin; 50-200 g/kg of oil for injection; oleic acid 0.3-3 g/kg; 10-50 g/kg of glycerol; 80-120 ml/kg of ethanol. The invention applies emulsification and solubilization technology, and adds ethanol to dissolve and compound ozagrel and a proper amount of egg yolk lecithin. Oleic acid is used as a co-emulsifier and a pH regulator, so that the free ozagrel in a water phase can be reduced, and the encapsulation efficiency and stability of the preparation are improved. After partial ethanol in the compound is removed by decompression concentration, emulsification and homogenization are carried out, and the drug-loading rate can be improved. The ozagrel fat emulsion injection prepared by the invention has higher stability and safety.
Brothers or sisters of the patients (n=125). Collection of blood, urine and stools at inclusion.
Safety and effectiveness of HETLIOZ for the treatment of Non-24 in pediatric patients have not been established.

Safety and effectiveness of HETLIOZ LQ oral suspension for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) have been established in pediatric patients 3 years and older. Use is based on a placebo-controlled crossover study of pediatric and adult patients [see Clinical Studies (14.2)].

Safety and effectiveness of HETLIOZ for the treatment of nighttime sleep disturbances in SMS have not been established in patients younger than 3 years old.

Juvenile Animal Toxicity Data   
Juvenile rats received oral doses of tasimelteon at 50, 150, or 450 mg/kg from weaning (day 21) through adulthood (day 90). These doses are approximately 12 to 108 times the maximum recommended human dose (MRHD) of 20 mg based on a mg/m2 body surface area. Toxicity was observed mainly at the highest dose and included mortality (females only), tremors, unsteady gait, decrease in growth and development compared to controls. The former reflected as decreases in bone growth, bone mineral content, bone ossification, and a delay in attainment of sexual maturation. Tasimelteon had no effect on fertility, reproduction, or learning and memory. The No Observed Adverse Effect Level (NOAEL) is 150 mg/kg/day, which is approximately 178 times the MRHD based on AUC.
Cardiopoiesis-primed human stem cells exert sustained benefit in treating heart failure despite limited retention following myocardial delivery. To assess potential paracrine contribution, the secretome of cardiopoiesis conditioned versus naïve human mesenchymal stromal cells was decoded by directed proteomics augmented with machine learning and systems interrogation. Cardiopoiesis doubled cellular protein output generating a distinct secretome that segregated the conditioned state. Altering the expression of 1035 secreted proteins, cardiopoiesis reshaped the secretome across functional classes. The resolved differential cardiopoietic secretome was enriched in mesoderm development and cardiac progenitor signaling processes, yielding a cardiovasculogenic profile bolstered by upregulated cardiogenic proteins. In tandem, cardiopoiesis enhanced the secretion of immunomodulatory proteins associated with cytokine signaling, leukocyte migration, and chemotaxis. Network analysis integrated the differential secretome within an interactome of 1745 molecules featuring prioritized regenerative processes. Secretome contribution to the repair signature of cardiopoietic cell-treated infarcted hearts was assessed in a murine coronary ligation model. Intramyocardial delivery of cardiopoietic cells improved the performance of failing hearts, with undirected proteomics revealing 50 myocardial proteins responsive to cell therapy. Pathway analysis linked the secretome to cardiac proteome remodeling, pinpointing 17 cardiopoiesis-upregulated secretome proteins directly upstream of 44% of the cell therapy-responsive cardiac proteome. Knockout, in silico, of this 22-protein secretome-dependent myocardial ensemble eliminated indices of the repair signature. Accordingly, in vivo, cell therapy rendered the secretome-dependent myocardial proteome of an infarcted heart indiscernible from healthy counterparts. Thus, the secretagogue effect of cardiopoiesis transforms the human stem cell secretome, endows regenerative competency, and upregulates candidate paracrine effectors of cell therapy-mediated molecular restitution.
The present invention is a novel, water-insoluble, cation-complexed anionic polysaccharide that is readily dispersible into aqueous media to provide an ingestible composition having a low viscosity. An important aspect of the present invention is that it provides such compositions that are heat sterilizable. Furthermore, the water-insoluble, cation-complexed anionic polysaccharide of the present invention cause no or minor increases to the viscosity of such liquids that contain at least one member selected from the group consisting of proteins, peptides and amino acids. Another aspect of the invention concerns a method for administering an antidiarrheal composition to a human, said antidiarrheal composition comprising at least one water-insoluble, cation-complexed anionic polysaccharide dispersed in an aqueous medium. These compositions are useful as a nutritional means of improving gastrointestinal function including bowel function and increasing absorption of organic nutrients, inorganic nutrients and water by the gastrointestinal tract. In another aspect of the present invention is provided a novel method of preparing a water-insoluble, cation-complexed anionic polysaccharide comprising wetting a starting anionic polysaccharide with water to a total solids content of about 30 to 70%, adding a cation and then milling. In yet another aspect of the present invention is provided a composition comprising a water-insoluble, cation-complexed anionic polysaccharide. This invention also provides a low viscosity, feeding composition providing an individual's requirements for carbohydrates, proteins, lipids, vitamins, minerals and at least one substantially water-insoluble, cation-complexed anionic polysaccharide in an aqueous medium. This same composition may be prepared in a dehydrated state and then subsequently rehydrated when ready for use.
RECORLEV is associated with dose-related QT interval prolongation. QT interval prolongation may lead to life-threatening ventricular dysrhythmias such as torsades de pointes. During Studies 1 and 2, which excluded patients with baseline QTcF interval greater than 470 msec, 4 (2.4%) patients experienced QTcF>500 msec, and 23 (14.7%) patients experienced change-from-baseline QTcF >60 msec. Resolution typically occurred following a dosage interruption and in some cases correction of electrolyte abnormalities.

RECORLEV may also elevate plasma concentrations of certain drugs known to prolong QT intervals. Prolongation of the QT interval from certain drugs can result in life-threatening ventricular dysrhythmias such as torsades de pointes [see Drug Interactions ( 7.1, 7.2)] . 

RECORLEV is contraindicated in patients taking other drugs known to cause QT interval prolongation associated with ventricular arrhythmias, including torsades de pointes, and is contraindicated in patients with a prolonged QTcF interval of greater than 470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or long QT syndrome (including first-degree family history) [see Contraindications ( 4), Drug Interactions ( 7.1, 7.2)]. 

Use RECORLEV with caution in patients with other risk factors for QT prolongation, such as congestive heart failure, bradyarrhythmias, and uncorrected electrolyte abnormalities, with more frequent ECG monitoring considered.

Obtain a baseline QT interval measurement and regularly monitor ECG for an effect on the QT interval during RECORLEV treatment. Correct hypokalemia and/or hypomagnesemia prior to RECORLEV initiation and monitor periodically during treatment [see Dosage and Administration ( 2.1, 2.3)] . Temporarily discontinue RECORLEV if the QTcF interval exceeds 500 msec. After the QTcF interval returns to less than 500 msec and contributing factors are corrected, re-institution of RECORLEV at a lower dose may be considered. If QT interval prolongation recurs after restarting RECORLEV, permanently discontinue RECORLEV [see Dosage and Administration ( 2.4)] .
A system is provided enabling do it yourself body stencilling and/or body art. In particular, the system of the invention provides a body tight removable mask that masks an area of the body for body painting. The mask is sized to fit a particular portion of the torso or an appendage of a subject individual, and masks a standard area to enable an unskilled artist to paint a portion of the subject individual. The stencil can mask a logo of a sports team or other form such as a swimsuit form on a wrist or ankle or upper torso, forehead, or a bathing suit area of the subject individual. The system optionally includes adhesive, Velcro, or other interlocking overlapping portions enabling easy removal of the stencil without disturbing the freshly painted area. In its simplest form, the stencil is a mask of the thighs, and the waste, the lower chest area and upper chest area, for example, with a preferably elastic mask panel that can be easily removed once the basic painting is complete. Advantageously, the invention enables websites that feature body painting, such as Sports teams, Universities, Sports Illustrated or Fashion TV, to sell stencil product in association with displays of body painted models.
BACKGROUND: Diagnostic error can result in pancreatoduodenectomy (PD) being mistakenly performed for benign disease. The aims of this study were to observe the error rate in PD over three decades and identify characteristics of benign disease that can mimic malignancy.
METHODS: Patients with a benign histological diagnosis after having PD performed for suspected malignancy between 1988 and 2019 were selected for review. Preoperative clinical features, imaging and pathological samples were reviewed alongside resection specimens to identify features that may have led to misdiagnosis.
RESULTS: Over the study period, 1812 patients underwent PD for suspected malignancy and 97 (5.2 %) of these had a final benign diagnosis. The rate of benign cases reduced across the study period. Some 62 patients proceeded to surgery without a preoperative tissue diagnosis; the decision to operate was made upon clinical and radiologic features alone. There were six patients who had a preoperative pathological sample suspicious for malignancy, of which two had autoimmune pancreatitis in the postoperative histology specimen.
DISCUSSION: Benign conditions, notably autoimmune and chronic pancreatitis, can mimic malignancy even with the use of EUS-FNA. The results of all available diagnostic modalities should be interpreted by a multidisciplinary team and honest discussions with the patient should follow.
Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis. Supraventricular and ventricular arrhythmias have been observed in the high-risk population treated. In some patients, injections of milrinone and oral milrinone have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. The potential for arrhythmia, present in congestive heart failure itself, may be increased by many drugs or combinations of drugs. Patients receiving milrinone should be closely monitored during infusion.

Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter/fibrillation which is not controlled with digitalis therapy.

During therapy with milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure.

If prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, milrinone should be cautiously administered with monitoring of blood pressure, heart rate, and clinical symptomatology.

There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours. Cases of infusion site reaction have been reported with intravenous milrinone therapy (see ADVERSE REACTIONS). Consequently, careful monitoring of the infusion site should be maintained to avoid possible extravasation.
Participants will undertake the first three training sessions in the outpatient clinic under the supervision of the specialized staff for familiarization with the intervention. and then the participants will proceed with the telerehabilitation program at their homes. Participants will undergo an exercise - based program 3 times/week, comprised of 10' warm up exercises, 40' aerobic, resistance and balance exercises and 10' cool down, with the use of wearable sensors.