anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Carcinogenesis   
In a 104-week carcinogenicity study, rats were administered daily oral doses up to approximately 8 times the maximum recommended human daily dose. There were no significant drug-induced tumor findings in male or female rats. The high dose male group was terminated early in the study (Week 93) due to excessive toxicity, and data from this group were not included in the statistical evaluation of the study results. In an 80-week carcinogenicity study, mice were administered daily oral doses approximately 6.5 times the human dose. There were no significant drug-induced tumor findings in male or female mice. 

Mutagenesis   
Risedronate did not exhibit genetic toxicity in the following assays: In vitro bacterial mutagenesis in Salmonella and E. coli (Ames assay), mammalian cell mutagenesis in CHO/HGPRT assay, unscheduled DNA synthesis in rat hepatocytes and an assessment of chromosomal aberrations in vivo in rat bone marrow. Risedronate was positive in a chromosomal aberration assay in CHO cells at highly cytotoxic concentrations (greater than 675 mcg/mL, survival of 6% to 7%). When the assay was repeated at doses exhibiting appropriate cell survival (29%), there was no evidence of chromosomal damage. 

Impairment of Fertility   
In female rats, ovulation was inhibited at an oral dose approximately 5 times the human dose. Decreased implantation was noted in female rats treated with doses approximately 2.5 times the human dose. In male rats, testicular and epididymal atrophy and inflammation were noted at approximately 13 times the human dose. Testicular atrophy was also noted in male rats after 13 weeks of treatment at oral doses approximately 5 times the human dose. There was moderate-to-severe spermatid maturation block after 13 weeks in male dogs at an oral dose approximately 8 times the human dose. These findings tended to increase in severity with increased dose and exposure time. 

Dosing multiples provided above are based on the recommended human dose of 30 mg/day and normalized using body surface area (mg/m2). Actual doses were 24 mg/kg/day in rats, 32 mg/kg/day in mice, and 8, 16 and 40 mg/kg/day in dogs.
Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.
<P>PROBLEM TO BE SOLVED: To provide a new method for searching drugs of viral infectious disease, neoplasm or the like.  <P>SOLUTION: The method for screening 2-5A system activating substances comprises following steps of [I]-[iii]. The step [i] comprises contact of a polypeptide comprising a specific amino acid sequence, active fragments or active derivatives of the amino acid sequence with a nucleotide substrate comprising adenyl (2'-5')adenosine as partial structure in the presence or absence of a specimen. The step [ii] comprises measurement of a degree of hydrolysis of the nucleotide substrate. The step [iii] comprises judgment of the specimen as positive when the degree of the hydrolysis in the presence of the specimen is small as compared to that in the absence of the specimen.  <P>COPYRIGHT: (C)2004,JPO
The present disclosure relates to privacy-preserving personalized fitness recommendations. In some implementations, a computing system may be configured to present privacy-preserving personalized fitness recommendations. In some implementations, the fitness application of system 100 may generate fitness recommendations based on fitness items previously performed by the user within and/or outside of the fitness application. For example, a user may engage in an internal fitness item presented by a fitness application or an external fitness item that is conducted without the assistance of the fitness application and detected during the external fitness item by one or more sensors of a user device carried by the user. Various attributes of the fitness items may be stored as historical fitness data and used by the fitness application to recommend user fitness items available through the fitness application or corresponding fitness service to the user. Fitness recommendations may be generated on the user device to protect the privacy of the user's personal health information.
The present invention provides a composition for enhancing the pharmacological activity of a water-soluble silicate polymer which comprises the water-soluble silicate polymer and a saturated fatty acid in pharmaceutically effective amounts for use as a medicine such as anti-allergic agent. The water soluble silicate polymers used according to the present invention may be obtained by polymerization and/or by extraction from plants, animals or fungi, or inflammatory tissue. The saturated fatty acid contained as an effective ingredient in the pharmaceutical composition of the present invention may be a straight chain or branched chain saturated fatty acid having about 8 carbon atoms to about 26 carbon atoms. The saturated fatty acid and water-soluble silicate polymer, effective ingredients of the present invention, can be formulated for various pharmaceutical compositions by combining with a suitable carrier or diluent for medical use. The composition of the present invention can suppress histamine release induced by a structural change in the cell membrane of the mast cell. It exhibits an excellent organism maintaining function such as cell protecting action and, therefore, is useful as a medicine such as an anti-allergic or anti-inflammatory agent.
The importance for training balance in connection with rehabilitation aimed at improving gait is easily stressed by considering the complex motor behaviour underpinning more challenging conditions than linear walking, as walking-and-turning, where the turn-related changes in feet, trunk and head movements are integral part of he kinematics of the steering body (Courtine and M. Schieppati, 2003; Crenna et al, 2007). It is no wonder that freezing of gait and increased risk of falling (Schlenstedt et al., 2016) is associated with abnormal bilateral coordination and turning. Hence, the present investigation somehow diverges from the theory of the task-specific training (Bayona et al., 2005), but considers instead the relevance for locomotion enhancement of training balance control, by hypothesising that specific balance rehabilitation might be sufficient for gait improvement. Here, we trained PD patients with two different treatments, both specifically addressing balance. A platform onto which subjects stood moved in antero-posterior, latero-lateral and diagonal direction in the horizontal plane. A simpler moving-platform protocol had been previously exploited for testing and enhancing balance capacities in patients with PD and with vestibular deficit (Nardone et al., 2010; De Nunzio 2007). This platform protocol challenges both the anticipatory and the reactive capacities to the ongoing postural perturbations, thereby training dynamic balance control, aiming at the balance problems encountered during every day activity.

The outcome of the platform treatment was compared to that obtained in another group of matched patients with PD by standardized and validated exercises aimed at training balance and dynamic balance (Renfro et al., 2016). Of note, these exercises contained no dynamic component (i.e. gait-related exercises) of balance training, contrary to Conradsson et al. 2017. Both treatments (platform and exercises) were tailored to the patient individual capacities, and their difficulty gradually increased all along the duration of the treatment (Conradsson et al., 2017). In this context, we estimated any improvement in balance control by indexes of dynamic stability during a balance perturbation test on the mobile platform and by clinical scores related to dynamic balance control. Gait improvement was both evaluated instrumentally and assessed by a functional clinical test.
Hypermobile Ehlers-Danlos syndrome (EDS) is an inherited condition marked by joint hypermobility, instability, chronic pain and fatigue, significantly impacting quality of life and autonomy. Management focuses solely on symptom alleviation. After experiencing a rapid decline in functional abilities, a patient in late adolescence with hypermobile EDS underwent hippotherapy rehabilitation (30 hours). She saw substantial improvements in fatigue, chronic pain and regained walking abilities. Hippotherapy played a crucial role in refining her postural balance, motor skills, proprioception, muscle function and endurance. It also positively affected her cognitive and emotional regulation by stimulating sensory inputs that activate neural pathways, providing relief from pain and fatigue. Notably, the patient transitioned from wheelchair reliance to walking with crutches, and then greatly enhanced both gait quality and speed. These findings demonstrate the relevance of hippotherapy for the rehabilitation of hypermobile EDS, reducing the need for pharmacological interventions and fostering a proactive approach to future challenges.
A medical device includes a controller having a microcomputer and sensor for monitoring and collecting data relating to a patient's compliance with a recommended or prescribed regimen for use of the medical device. The controller is battery operated and is recharged by placing the controller into a cradle which has a wall plug for providing power to the cradle and the controller. The cradle also has a modem and phone connection so that as the controller rests in the cradle, compliance data contained within the controller is automatically transmitted by a modem over the phone line connection to a central location. The central location includes a data network for receiving the patient compliance data, processing and storing it in virtual patient files, and one or more web servers host a web site for displaying the patient data in its processed form. Access to the web site is secure and allows a patient to view her own data. Additionally, medical professionals may access the web site not only to view data relating to all of their patients data but also to record data corresponding to patient information obtained during office visits which is then also processed for further display on the web site.
This study is a randomised controlled trial (RCT) comparing an online mindfulness based course (10ofZen) with a treatment as usual group (delayed 10ofZen course materials). Participants will be informed about the study and asked to undertake a screening questionnaire to ensure the eligibility criteria is met. Following this, participants will be invited to give online consent. A battery of self-report measures will be administered online at baseline (week 0), post-intervention (week 10) and at follow-up (week 14). A sleep measure will also be undertaken and used as a co-variate during data analysis. At the end of participation in the research study, all participants will gain access to the course materials, including audio recordings of meditations and any written materials used within the course.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 30,000 Americans each year. Of these 30,000 Americans, it has been suggested that up to 50% will experience cognitive and behavioral changes in the form of frontotemporal dysfunction and up to 40% will meet criteria for frontotemporal dementia (FTD). Riluzole the only FDA approved agent for ALS extends a patient's lifespan by 2-3 months, and there are no proven therapies for the cognitive changes associated with ALS. More effective therapy for this universally fatal disease is desperately needed.

Results from an open label pilot trial of 20 patients treated with memantine at 10 mg twice a day suggested that treatment with the combination of memantine and riluzole slowed ALS disease progression. This trial also showed that levels of specific protein biomarkers in the cerebrospinal fluid (CSF) at baseline correlated with the rate of disease progression. A concurrent phase II study performed by Dr. Carvalho, found no effect with similar dosing; however, the study was limited in terms of power. Comments on previous failed drug trials in ALS have raised the concern that many ALS trials study a potential therapeutic agent at only a single dose and thus may miss the potential efficacy of non FDA approved doses; therefore, this proposed study will test a higher dose of memantine, 20 mg twice a day, in a double blind, placebo controlled, randomized trial of 90 patients with ALS to determine if a therapy of memantine, especially in combination with riluzole, can slow disease progression compared to treatment with riluzole alone or no treatment. Participants who experience treatment related adverse events may undergo dose reduction or discontinuation. The primary outcome measure will be the rate of disease progression as measured by the ALS Functional Rating Scale- Revised (ALSFRS-R). In addition the investigators will examine the cognitive deficits seen in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). Finally the investigators will examine specific validated protein serum biomarkers to determine if there is a correlation between the levels of these biomarkers and the rate of disease progression. In particular the investigators will measure the ratio of phosphorylated heavy neurofilament to Complement 3 to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine.

This project will offer unique insights into this untreatable disease. If this study confirms earlier results and suggests that memantine, when used in conjunction with riluzole, significantly slows down the progression of the disease, as well as ameliorates cognitive deficits in patients with fronto-temporal dysfunction, it will set the groundwork for conducting a larger phase III trial.
The incidence of type 2 diabetes has increased steadily over the last three decades. Although medical nutrition therapy is an integral component of diabetes management, nutrition recommendations for diabetes have often been based on clinical experience and expert consensus, rather than on carefully controlled clinical trials. The expert consensus on medical nutrition therapy is that carbohydrate and monounsaturated fat together should provide approximately 60-70% of total energy intake. This recommendation accommodates parties on both sides of a debate over what constitutes the optimal macronutrient composition of a diet for type 2 diabetic patients. On one side are proponents of high carbohydrate, low fat diets who contend that this regimen promotes the lowering of total- and LDL-cholesterol and is less calorically dense than diets containing a higher percentage of fat. On the other side are advocates of high monounsaturated fat, Mediterranean-type diets who cite data from short-term studies indicating that this approach decreases postprandial levels of plasma glucose, insulin, and triglycerides, and increases HDL-cholesterol more than isocaloric high carbohydrate diets. However, there is concern about the potential for high fat diets to increase energy intake and weight gain among free-living subjects. To make definitive, scientifically-based diet recommendations, it is essential that controlled long-term trials be conducted to demonstrate the health effects of specific percentages of monounsaturated fats and carbohydrates in the diets of persons with type 2 diabetes.
This invention teaches a means of rapidly producing a vaccine following a viral outbreak and using said vaccine to prevent the outbreak from becoming a pandemic. Said vaccine is composed of multiple immunostimulatory agents (agonists) incorporated in liposomes. Each agonist will bind to its specific cellular receptor and induce the cell to produce type 1 interferons which has strong anti-viral activity. The agonists are Poly IC, ssRNA, CpG-ODN and MPL-A incorporated in a liposomal vaccine. Using multiple different agonists in the vaccine will elicit a stronger innate immune response than using a single agonist. This vaccine can be enhanced by combining a viral antigen with the agonists in the liposome. Said enhanced vaccine will provide immediate and prolonged immunity to viral infection by stimulating both the innate immune response and the adaptive immune response against the virus.
Hypercholesterolemia and tobacco use interact to increase cardiovascular disease (USDHHS 1990; 2004). Smoking is a cause of metabolic syndrome and diabetes (Eliasson, 2003; Hu et al., 2001; Weitzman et al., 2005). Smokers live on average 13 years less than non-smokers (USDHHS, 2004), and tobacco remains the number one health threat in the United States (Mokdad, Marks, Stroup, \& Gerberding, 2004). The Public Health Service (PHS) has published a Guideline for Tobacco Dependence Treatment (Fiore, 2000; Fiore et al., 2008). Hypercholesterolemia is a major risk for cardiovascular disease, and effective treatment with lifestyle and medications lower the risk of cardiovascular events including sudden death, myocardial infarction, and stroke. The National Cholesterol Education Program (NCEP) has published clinical guidelines for its management (Brown, 2004). These include recommendations for therapeutic lifestyle change and medications.

The specific aims of the proposed work are: first, to determine abstinence from tobacco at 6-months and lower LDL-cholesterol from baseline to 6-months for patients assigned the VCRT in addition to the clinician compared to those just receiving clinician care; second, to test for increase in medication use (number of days of medication use-for tobacco dependence mediations and for statin medications for cholesterol) for those receiving the VCRT + clinician; third, to examine the self-determination process model, expanded to include autonomous motivation and perceived competence for medication adherence and actual adherence to promote maintained abstinence and lower LDL-cholesterol.
Patients in this arm will undergo usual clinical care as planned by their medical team. They will be asked to complete surveys at baseline, 3,6 and 12 months and for clinical outcome data during the observation period to be collected.
NEW MATERIAL:The compound of formula 1 (R is methyl or H), its reduced derivative, its monoacetyl derivative, and its oxidized derivative. EXAMPLE:8,9-Dimethoxy-1H-benzo[de][1,6]naphthyridine. USE:It has sympatholytic action and is useful as a hypotensor, etc. PROCESS:The compound of formula 1 can be prepared by homogenizing a sponge (Aaptos aaptos), extracting with a proper solvent, fractionating by chromatography, and recrystallizing with a solvent. The compound of formula 2 (a compound of formula 1 wherein R is methyl) is catalytically reduced in the presence of a catalyst such as platinum to obtain a novel reduced derivative of formula 5, which is acetylated with acetic anhydride in pyridine to the novel monoacetyl derivative of formula 6. The compound of formula 6 can be converted to the novel compound of formula 7 by ozone-oxidation followed by reduction with dimethyl sulfide, and further to the novel compound of formula 8 by repeating the above process.
PROBLEM TO BE SOLVED: To obtain a detergent composition having a refreshing touch without losing foaming properties possessed by a detergent and without making the skin tense by formulating a cationic polymer and an amphoteric polymer together. SOLUTION: This detergent composition comprises an amphoteric polymer composed of a unit represented by the formula (R1 and R2 are each H or methyl; (x), (y) and (z) are each a positive integer) and a cationic polymer. A polydimethylmethylenepiperidium chloride, a cationized cellulose, a cationized guar gum or a diallyl quaternary ammonium salt/alkylamide copolymer, or the like, are cited as the cationic polymer. As the amphoteric polymer, e.g. Merquat Plus 3330(R) (manufactured by Calgon Corporation) is cited as a commercially available product. The amount of the compounded amphoteric polymer is preferably 0.001-5.0 wt.%, more preferably 0.01-2.0 wt.% in the detergent composition and the amount of the compounded cationic polymer is preferably 0.001-5.0 wt.%, more preferably 0.01-2.0 wt.% in the detergent composition.