anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
### Teratogenic Effects: Pregnancy Category C

No drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and acetaminophen. The tramadol/acetaminophen combination product was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/434 mg/kg tramadol/acetaminophen (300/2604 mg/ m2 or 1.6 times the maximum daily human tramadol/acetaminophen dosage of 185/1591 mg/ m2), but was not teratogenic at this dose level. Embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs.

### Non-teratogenic effects

Tramadol alone was evaluated in peri- and post-natal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/ m2 or 1.6 times the maximum daily human tramadol dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/ m2 or 2.6 times the maximum daily human tramadol dosage).

There are no adequate and well-controlled studies in pregnant women. Tramadol hydrochloride and acetaminophen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol hydrochloride during post-marketing.
Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 men and 143 women, aged 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m2) using a combination of targeted and suspect screening approaches. Bacterial species were identified based on whole-genome shotgun sequencing (WGS) of DNA extracted from stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings from the human study with metabolic implications of exposure to perfluorooctanoic acid (PFOA) in PPARα-humanized mice. Serum levels of twelve ETs were associated with obesity and insulin resistance. High chemical exposure was associated with increased abundance of several bacterial species (spp.) of genus (Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum, and Veillonella), particularly in men. Conversely, females in the higher exposure group, showed a decrease abundance of Prevotella copri. High concentrations of ETs were correlated with increased levels of secondary BAs including lithocholic acid (LCA), and decreased levels of ursodeoxycholic acid (UDCA). In silico causal inference analyses suggested that microbiome-derived secondary BAs may act as mediators between ETs and obesity or insulin resistance. Furthermore, these findings were substantiated by the outcome of the murine exposure study. Our combined epidemiological and mechanistic studies suggest that multiple ETs may play a role in the etiology of obesity and insulin resistance. These effects may arise from disruptions in the microbial biosynthesis of secondary BAs.
NEW MATERIAL:The aphidicolin derivative of formula I. USE:Useful as a carcinostatic agent applicable by oral or parenteral administration. It is converted to pharmaceutical preparation by using a surfactant, vehicle, lubricant, adjuvant, etc. The ratios of the above components in the preparation are e.g. 0.3-15wt% active component, 85-99.4% vehicle such as lactose, 0-20% lubricant such as magnesium stearate, 0-20% surfactant such as alcohol and 0.3-20% film-forming substance such as cellulose. PREPARATION:The compound of formula I can be produced by reacting the compound of formula II with crotonic anhydride in a solvent such as pyridine in an inert gas stream at room temperature for 12-24hr.
PURPOSE:To provide an eye drop containing pranoprofen and boric acid as active components, having strong anti-inflammatory activity, little irritation and no side effect, and applicable to herpetic ophthalmia. CONSTITUTION:The objective agent contains pranoprofen as an active anti- inflammatory component and boric acid as an isotonic agent. Pranoprofen (chemical name: alpha-methyl-5H[1]benzopyrano(2,3-b)pyridine-7-acetic acid) has anti- inflammatory, analgesic and antipyretic activities, and exhibits excellent effect to inflamation and pain. The standard concentration of pranoprofen is usually 0.01-0.5(w/v)%. The amount of boric acid is determined to give an osmotic pressure ratio of about 1, and is usually about 0.5-2(w/v)%. The pH of the eye drop is preferably about 6.5-8.5, especially about 7.5.
Tuberculosis (TB) is a serious public health issue in India. Numerous molecular mechanisms and immunological responses play significant roles in the pathogenesis of tuberculosis. This study aimed to identify host immune-related biomarkers that are significantly differentially expressed in active TB and that play a vital role in disease progression. The methodology employed in this study included data collection, pre-processing, analysis, and interpretation of the results. Six microarray datasets were used to identify differentially expressed genes (DEGs), and only the common DEGs were used for further downstream analysis, such as hub gene identification, gene ontology, pathway enrichment analysis, and drug-gene interaction analysis. The study identified 1728 DEGs, including 906 upregulated and 822 downregulated genes. Five hub genes were identified that were: STAT1, GBP5, GBP1, FCGR1A, and BATF2. Gene ontology and pathway enrichment revealed that most of the genes were involved in interferon-gamma signaling. In addition, through drug-gene interactions, known drugs have been identified for STAT1, FCGR1A and GBP1. The findings of this study may contribute to early detection and treatment of active TB.
NEW MATERIAL:A compound shown by the formula I [R<1> is 1-8C alkyl, or group shown by the formula II (n is 1-3)]. EXAMPLE:alpha-( 3,5-Ditertiary-butyl-4-methanesulfonyloxybenzylidene)-gamma-butyrolactone shown by the formula III. USE:An ultraviolet light absorber and an inhibitor of blood platelet aggregation. Having strong inhibiting action on blood platelet aggregation, capable of inhibiting completely blood platelet aggregation by adding 1mug/ml compound shown by the formula III. PREPARATION:alpha-(3,5-Ditertiary-butyl-4-hydroxybenzylidene)-gamma-bu rtyrolactone is reacted with a sulfonyl halide shown by the formula R<1>SO2X (X is halogen) such as methanesulfonyl chloride, etc. in tetrahydrofuran solvent in the presence of a base such as NaH, etc. under reflux to give a compound shown by the formula I.
Couple-based physical activity intervention commencing 14 (+/-7) days post-transplant (8 sessions with a health counselor). Sessions 1-4 will train couples in the use of communal coping strategies to support one another in achieving PA goals. Skill building will focus on instruction and practice in adaptive communication, with emphases on adaptive speaking, responsive listening, and joint decision-making and problem-solving around PA. Instruction and practice will focus specifically on communication about PA and working together (we versus me) to increase PA. Sessions 5-8 will afford check-in, review of PA progress, and troubleshooting any barriers to PA. All sessions will be dyad-based but will include delivery of individualized step goals for the next week using an adaptive approach and based on remotely-monitored Fitbit step data. Specifically, the 75th percentile rank of each participant's last 7 days of recorded days will serve as the step goal prescription for the next week.
Solifenacin Succinate Tablets were evaluated in four twelve-week, double-blind, randomized, placebo-controlled, parallel group, multicenter clinical trials for the treatment of overactive bladder in adult patients having symptoms of urinary frequency, urgency, and/or urge or mixed incontinence (with a predominance of urge). Entry criteria required that patients have symptoms of overactive bladder for ≥ 3 months duration. These studies involved 3027 patients (1811 on Solifenacin Succinate Tablets and 1216 on placebo), and approximately 90% of these patients completed the 12-week studies. Two of the four studies evaluated the 5 and 10 mg Solifenacin Succinate Tablets doses (Studies 1 and 2) and the other two evaluated only the 10 mg dose (Studies 3 and 4). All patients completing the 12-week studies were eligible to enter an open-label, long-term extension study (Study 5) and 81% of patients enrolling completed the additional 40-week treatment period. The majority of patients were Caucasian (93%) and female (80%) with a mean age of 58 years.

The primary endpoint in all four trials was the mean change from baseline to 12 weeks in number of micturitions/24 hours. Secondary endpoints included mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition.

The efficacy of Solifenacin Succinate Tablets was similar across patient age groups and gender. The mean reduction in the number of micturitions per 24 hours was significantly greater with Solifenacin Succinate Tablets 5 mg (2.3; p < 0.001) and Solifenacin Succinate Tablets 10 mg (2.7; p < 0.001) compared to placebo (1.4). The mean reduction in the number of incontinence episodes per 24 hours was significantly greater with Solifenacin Succinate Tablets 5 mg (1.5; p < 0.001) and Solifenacin Succinate Tablets 10 mg (1.8; p < 0.001) treatment groups compared to the placebo treatment group (1.1). The mean increase in the volume voided per micturition was significantly greater with Solifenacin Succinate Tablets 5 mg (32.3 mL; p < 0.001) and Solifenacin Succinate Tablets 10 mg (42.5 mL; p < 0.001) compared with placebo (8.5 mL).

The results for the primary and secondary endpoints in the four individual 12-week clinical studies of Solifenacin Succinate Tablets are reported in Tables 3 through 6.
The alarming rates of obesity among children and adults, particularly among ethnic minorities, has been identified by the National Institutes of Health as one of the most serious public health challenges facing our nation in the 21st century. South Carolina (SC), part of the "Stroke Belt," has the 3rd highest obesity rate among US children at 39.2% and the 12th highest obesity rate among US adults at 32.3%. Unfortunately, African Americans in SC are disproportionately more likely to be overweight or obese (75.7% of adults, 40% of children), which places them at considerable high-risk for obesity-related diseases such as asthma, Type 2 diabetes, cardiovascular disease, hypertension, stroke, and some forms of cancer. This public health challenge is compounded by the lack of available intervention strategies specially tailored to meet the unique needs of ethnic minorities. This R01 randomized clinical trial, informed by the results from a recently completed NHLBI/NICHD center grant ("FIT Families Project," U01HL097889; PI-Naar) that followed the National Heart, Lung, and Blood Institute, Obesity Related Behavioral Intervention Trials (ORBIT) model for developing behavioral interventions, will examine the efficacy of FIT Families compared to a credible attention control condition. Each of four evidence-based behavioral components of FIT Families (home-based services, contingency management, motivational interviewing, cognitive behavioral skills training) were culturally tailored and optimized through a proof of concept sequential multiple randomized trial that produced weight loss among African American adolescents, a large and understudied population. One hundred and eighty obese African American adolescents aged 12-17 and their primary caregiver will be randomly assigned to one of two treatment conditions: 1) FIT Families or 2) Home-Based Family Support (HBFS) attention control condition. It is predicted that FIT Families will lead to greater reductions in adolescent and caregiver percent overweight, and increases in physical activity and the use of evidence-based weight management behaviors (self-monitoring of diet and exercise). If effective, FIT Families, which was carefully developed and adapted through successive Phases of ORBIT, has the potential to reduce disparities in obesity-related diseases (cardiovascular and metabolic) by addressing multiple risk factors among African American families and their adolescent children. Thus, this project has high significance in terms of potential public health impact and reduction in obesity related healthcare costs.
Retinal Vein Occlusion

In the pooled safety population [see Adverse Reactions (6.1)] of MEKINIST monotherapy, the incidence of retinal vein occlusion (RVO) was 0.6%. In the pooled safety population [see Adverse Reactions (6.1)] of MEKINIST administered with dabrafenib, there were no cases of RVO. RVO may lead to macular edema, decreased visual function, neovascularization, and glaucoma.

Urgently (within 24 hours) perform ophthalmological evaluation for patient-reported loss of vision or other visual disturbances. Permanently discontinue MEKINIST in patients with documented RVO [see Dosage and Administration (2.4)]. 

Retinal Pigment Epithelial Detachment

Retinal pigment epithelial detachment (RPED) can occur with MEKINIST. Retinal detachments may be bilateral and multifocal, occurring in the central macular region of the retina or elsewhere in the retina. In melanoma and NSCLC trials, routine monitoring of patients to detect asymptomatic RPED was not conducted; therefore, the true incidence of this finding is unknown. 

MEKINIST Administered with Dabrafenib (Pediatric): In the pooled safety population, RPED events occurred in < 1% of patients.

Perform ophthalmological evaluation periodically and at any time a patient reports visual disturbances. Withhold MEKINIST if RPED is diagnosed. If resolution of the RPED is documented on repeat ophthalmological evaluation within 3 weeks, resume MEKINIST at same or reduced dose. If no improvement after 3 weeks, resume MEKINIST at reduced dose or permanently discontinue MEKINIST [see Dosage and Administration (2.4)].
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.
PURPOSE:To obtain a hair producing and growing promoter having extremely high safety to skin, comprising a compound having an aconitine type chemical structure or its salt as an active ingredient. CONSTITUTION:A hair producing and growing promoter comprising a compound shown by the formula (R1 and R2 are H, saturated or unsaturated alkyl which may be substituted, aliphatic or aromatic acyl which may be substituted, or aralkyl which may be substituted; R3 is H, OH, aliphatic or aromatic acyloxy; R4 is H or OH; R5 is H, OH, lower alkoxy or aliphatic acyloxy; R6 is H, OH or R6 and forms carbonyl with a carbon atom at the 15-position; R7 is H, methyl, aliphatic acyl or aromatic acyl) or its salt, such as 8-deoxy-14-O- benzoylmesaconine as an active ingredient. The compound is isolated from Aconitum chinense Sieb. or a substance having reduced toxicity prepared by heat-treating Aconitum chinense Sieb. (e.g. processed aconite obtained by pressurizing and heat treatment). Or the compound is produced from an aconitine type alkaloid such as aconitine, mesaconitine, hypaconitine or diesaconitine as a starting substance.
INTRODUCTION: Neurodevelopmental disorders (NDDs) are diverse and can be explained by either genomic aberrations or single nucleotide variants. Most likely due to methodological approaches and/or disadvantages, the concurrence of both genetic events in a single patient has hardly been reported and even more rarely the pathogenic variant has been regarded as the cause of the phenotype when a chromosomal alteration is initially identified.
CASE PRESENTATION: Here, we describe a NDD patient with a 6p nonpathogenic paracentric inversion paternally transmitted and a de novo pathogenic variant in the GRIN2B gene. Molecular-cytogenetic studies characterized the familial 6p inversion and revealed a paternal 9q inversion not transmitted to the patient. Subsequent whole-genome sequencing in the patient-father dyad corroborated the previous findings, discarded inversions-related cryptic genomic rearrangements as causative of the patient's phenotype, and unveiled a novel heterozygous GRIN2B variant (p.(Ser570Pro)) only in the proband. In addition, Sanger sequencing ruled out such a variant in her mother and thereby confirmed its de novo origin. Due to predicted disturbances in the local secondary structure, this variant may alter the ion channel function of the M1 transmembrane domain. Other pathogenic variants in GRIN2B have been related to the autosomal dominant neurodevelopmental disorder MRD6 (intellectual developmental disorder, autosomal dominant 6, with or without seizures), which presents with a high variability ranging from mild intellectual disability (ID) without seizures to a more severe encephalopathy. In comparison, our patient's clinical manifestations include, among others, mild ID and brain anomalies previously documented in subjects with MRD6.
CONCLUSION: Occasionally, gross chromosomal abnormalities can be coincidental findings rather than a prime cause of a clinical phenotype (even though they appear to be the causal agent). In brief, this case underscores the importance of comprehensive genomic analysis in unraveling the wide-ranging genetic causes of NDDs and may bring new insights into the MRD6 variability.
PURPOSE: To provide new crystalline carbapenem compound consisting of a specific thiazolin-2-yl-azetidin-5-yl-thio-carbapenemcarboxylic acid compound of crystalline state, exhibiting excellent antibacterial activity and storage stability and useful e.g. as an antibacterial agent for oral administration. CONSTITUTION: This new crystalline carbapenem compound exhibiting excellent antibacterial activity and storage stability and useful e.g. as an antibacterial agent for oral administration is (1R,5S,6S)-2-[1-(thiazolin-2-yl)azetidin-3- yl]thio-6-[(R)-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid of formula I. The compound can be produced by reacting a 2-diphenylphosphoryloxy- carbapenem compound of formula II (PNB is p-nitrobenzyl) with 3- mercapto-1-(thiazolin-2-yl)azetidine hydrochloride of formula III and removing the protecting groups of the product. The obtained amorphous compound is dissolved in water and stirred for 30min at room temperature and then for 30min under ice cooling to obtain the crystalline compound of formula I.
PURPOSE:To obtain the titled cream having high brightness and saturation, giving excellent feeling to the skin and capable of easily removing dirt substance embedded in a dent such as skin pore, by using a coating foundation agent and magnetic particles coated with a whitening material. CONSTITUTION:Surface of magnetic particles (preferably having particle diameter of <=80mum) (composed of metals of Fe, Ni, Co, Mn, Cr, Cu, Ba or rare-earth elements, their alloy or ferrite which is oxide of the above metal) is coated with a white pigment having particle diameter of <=10mum, preferably <=5mum and a refractive index of >=1.6, preferably >=2.0 (e.g. rutile or anatase titanium oxide or zinc oxide) and the coated magnetic particles are used in combination with a coating foundation agent. An opaque polymer (e.g. polyolefin or polyamide) can be used as the whitening material. The incident light is scattered by the whitening material to obtain a magnetic cream exhibiting an appearance having high whiteness or brightness.
Participants will receive a starting dose of 625mg of ONC201 weekly on Day 1 and 2 during any non-interventional radiation/re-irradiation per standard of care treatment, and in combination with targeted agents to be selected from approved/available agents based on a rational therapy approach guided by molecular data from the tumor tissue or cerebral spinal fluid (CSF). Each individual targeted agent will be dosed at the recommended therapeutic dose, if a dose has been issued for the participant's age group. Observations and schedule of events will be issued based on the chosen agent determined to best fit the molecular profile (e.g. BRAFV600E, PDGFRA, FGFR1, NF1).
###  Usual Initial Dosage

PAXIL CR should be administered as a single daily dose, usually in the morning, with or without food. The recommended initial dose is 25 mg/day. Patients were dosed in a range of 25 mg to 62.5 mg/day in the clinical trials demonstrating the effectiveness of PAXIL CR in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, the full effect may be delayed. Some patients not responding to a 25-mg dose may benefit from dose increases, in 12.5-mg/day increments, up to a maximum of 62.5 mg/day. Dose changes should occur at intervals of at least 1 week.

Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.

###  Maintenance Therapy

There is no body of evidence available to answer the question of how long the patient treated with PAXIL CR should remain on it. It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Whether the dose of an antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of immediate-release paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg, which corresponds to a 37.5-mg dose of PAXIL CR, based on relative bioavailability considerations (see CLINICAL PHARMACOLOGY: Pharmacokinetics).