anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Patients with certain homozygous or compound heterozygous variants in the DPYD gene known to result in complete or near complete absence of DPD activity (complete DPD deficiency) are at increased risk for acute early-onset toxicity and serious, including fatal, adverse reactions due to XELODA (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity). Patients with partial DPD activity (partial DPD deficiency) may also have increased risk of serious, including fatal, adverse reactions.

XELODA is not recommended for use in patients known to have certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency.

Withhold or permanently discontinue XELODA based on clinical assessment of the onset, duration, and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe reactions, which may indicate complete DPD deficiency. No XELODA dose has been proven safe for patients with complete DPD deficiency. There are insufficient data to recommend a specific dose in patients with partial DPD deficiency.

Consider testing for genetic variants of DPYD prior to initiating XELODA to reduce the risk of serious adverse reactions if the patient's clinical status permits and based on clinical judgement [see Clinical Pharmacology (12.5)]. Serious adverse reactions may still occur even if no DPYD variants are identified.

An FDA-authorized test for the detection of genetic variants of DPYD to identify patients at risk of serious adverse reactions due to increased systemic exposure to XELODA is not currently available. Currently available tests used to identify DPYD variants may vary in accuracy and design (e.g., which DPYD variant(s) they identify).
Maximum strength protocol based on a Maximum Repetition (1RM). The aim of the application of the training is to produce an increase in strength based on training with high loads (80% 1RM), individually and covering the muscles of the lower extremity (quadriceps, hamstrings, gluteus maximus).
At the end of this initial week of monitoring, participants will be randomized to a control group or an intervention group. Both groups will be followed for three months, with outcome measurements collected monthly. Both arms will continue to receive their seven day physical activity assessment using the phone's core motion sensors and HealthKit/ Google Health step count. Both groups will also be prompted to complete monthly fitness tests: the 6-minute walk test, a 12 minute run test, and the Tecumseh step test.
We performed a single-center, prospective, randomized, double-blind, placebo-controlled and cross-over clinical study, in which patients received CPAP and sham therapy for two 12-week periods. Baseline measurements in healthy controls matched for age and gender were also obtained. At recruitment, 24-h blood pressure monitoring (ABPM), an echocardiogram (to rule out any cardiac dysfunction) and a sleep study was obtained in all participants . After fasting overnight, a venous blood sample (anti-coagulated with dipotassium EDTA, for 8-isoprostane and total nitrate and nitrite concentration (NOx) determinations) and a urine sample were collected in all of them between 08:00 and 10:00 hours. Within 30 minutes of blood collection, plasma was obtained by centrifugation at 3000 rpm for 15 min. All plasma samples were stored at -60°C until analysis. Patients with OSAS underwent a full-night CPAP titration study using an automated pressure setting device (Auto Set; ResMed, Sydney, Australia). Compliance with therapy was obtained from a built-in run-time counter. After 12 weeks, CPAP device was switched to the alternate mode of therapy and ABPM,, plasma and urine sampling were repeated in patients
PURPOSE: A pharmaceutical composition containing Morus alba extract is provided to protect cell from toxicity or thapsigargin. CONSTITUTION: A pharmaceutical composition for preventing and treating dementia contains Morus alba extract as an active ingredient. The extract is prepared using water, low carbon number alcohol, or mixture thereof. The dementia is Alzheimer's disease. A health functional food for preventing and treating dementia contains the extract as an active ingredient. A method for preparing the extract comprises: a step of adding extraction solvent to dry Morus alba and extracting; a step of filtering the extract; and a step of decompressing the extract.
A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.
The control group is retrospective. It will include patients who have been operated on for POVG in the surgical department No. 1 of the KPH during the last 3 years (25-35) and 5-10 patients who will be operated on within the next 6-8 months.
PROBLEM TO BE SOLVED: To obtain an excellent anticariogenic agent capable of inhibiting bacterial plaque formation by Streptococcus mutans by including a yucca extract. SOLUTION: This anticariogenic agent contains a yucca extract. For yucca, its terrestrial stems and other terrestrial parts (including seeds) are usable as materials for extraction; an extraction treatment thereof is carried out by grinding them to an appropriate size and then subjecting the resultant ground product to extraction with water or a hydrophilic organic solvent or their mixture. This anticariogenic agent may be in the form of liquid, solid or semi-solid and can be used in medicaments, quasi-drugs, compositions for oral cavity, and the like. The content of this anticariogenic agent in a composition for oral cavity is pref. 0.01-20 wt.%, more pref. 0.05-10 wt.%, in terms of yucca extract.
The present invention relates to high efficiency methods and compositions for stably integrating exogenous double-stranded DNA into the chromosomal DNA of sperm cells. The exogenous DNA to be integrated into the sperm is converted to a linear double stranded DNA possessing single-stranded cohesive ends, by contacting said exogenous DNA with a type II restriction enzyme that upon scission, generates such ends. The DNA to be cut can be a circular DNA such as in a plasmid, such that it possesses at least one recognition and cutting site outside of the genes or regulatory regions critical to the desired, post-integration function of the DNA, and no recognition and cutting sites within the critical regions. The exogenous DNA is then introduced into sperm cells, as is some of the type II restriction enzyme used above to generate the single-stranded cohesive ends on the exogenous DNA. The DNA and the corresponding restriction enzyme can be introduced into the sperm cells, together or sequentially, by electroporation or lipofection or by any other technique that preserves enough of said sperm's mobility and fertilization functions. The sperm containing the integrated exogenous DNA can then be used to fertilize eggs by artificial insemination, in vitro fertilization, or other fertilization methods known in the art, thereby producing transgenic animals wherein all or a plurality of cells now contain the exogenous DNA stably integrated into their respective genomes. The present invention also relates to transgenic animals or their descendants produced by methods or compositions herein disclosed. The present invention further relates to cells or cell lines derived from transgenic animals or their descendants produced by methods or compositions herein disclosed. The present invention further relates to proteins or other gene products encoded for by the exogenously introduced DNA isolated from said transgenic animals or their descendants. The present invention further relates to using the method of the present invention to produce transgenic animals resistant to diseases, and to the disease-resistant animals thereby produced.
BACKGROUND: Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD.
MAIN BODY: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I").
CONCLUSIONS: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.
Patients diagnosed with CRPS and control subjects will be enrolled in the study. The CRPS participants will be administered with phenylephrine (day 1) and clonidine (day 2). The control participants will not receive any intervention.

The aim of this study is to determine if expression of α1-adrenoceptors (α1-AR) altered in the skin of a subgroup of patients whose pain is associated with increased adrenergic sensitivity after nerve trauma. Increased adrenergic sensitivity will be determined by assessing pain in patients after administration of phenylephrine on day 1. Expression of α1-AR will be determined by taking skin biopsies on day 2 after administration of clonidine. Then, we will compare the expression of α1-AR in patients who were classified as having increased adrenergic sensitivity versus those who were not.
Differentiation in nature of erectile dysfunction (ED) is currently made by nocturnal erection detection with the RigiScan. The RigiScan uses outdated software, measurements are user unfriendly and system components are out of stock. In the search of modernizing erectile dysfunctions diagnostics, the question has arisen whether temperature measurements can function as a tool for nocturnal erection detection. With the absence of a pressure component, the patient experience should improve. Literature and mathematical modelling studies have shown that the penile temperature increases significantly during erection. However, it is unclear what the influence of environmental factors such as blankets and clothing is on the increase in penile temperature during erection. The Feeling Hot 1 study explores the effects of these environmental factors in a controlled setting to gain insight into the possibility of using temperature sensing to detect nocturnal erections.
Encapsulated nerve endings called mechanoreceptors are end components of afferent nerves and have specialized end organs surrounding the nerve terminal. Those receptors are concentrated in various human periarticular tissues. It is believed that these mechanoreceptors in the periarticular tissues are related to muscle reflexes. However, it is still unknown which type of mechanoreceptors contribute to the muscle reflexes and whether the mechanoreceptors excite and/or inhibit muscle activation. In the investigators previous studies, mechanoreceptors in the human proximal interphalangeal (PIP) joint and surrounding structures have been extensively examined. The investigators have identified that Pacini-like nerve endings in the PIP joint were found in substantial numbers in the junction of the C1 pulley and accessory collateral ligaments. The investigators hypothesize that the Pacini-like nerve endings in the junction of the C1 pulley generate activity in the associated flexor muscle/tendon in the finger.
Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.
PROBLEM TO BE SOLVED: To obtain the subject internal liquid preparation having reduced unpleasant taste attributable to iron, free from a metallic taste of calcium, etc., extremely pleasantly drinkable and useful for prophylax is of anaemia, etc., by compounding an organic iron compound with an organic acid and adjusting pH to a specific range. SOLUTION: This internal liquid preparation is obtained by compounding (A) an organic iron compound (preferably, ferric ammonium citrate) with (B) one or more kinds of organic acids in an amount of 0.05-2.0wt.% so that the organic acid(s) is 3-300 pts.wt. based on the 1 pt.wt. of the iron component in the component A, and the pH is adjusted to 2.5-5.0. Further, it is preferable that (C) 0.001-1.0wt.% of a calcium component is further added so that the content of the calcium component (preferably, calcium glucuronate) is 1-49 pts.wt. based on 1 pt.wt. of iron component in the component A, and the component B is an acid selected from citric acid, malic acid, fumaric acid, tartaric acid, lactic acid and succinic acid.
Collection of all quantitative ultrasonic data was performed by one ultrasound physician. The Aixplorer® series color ultrasonic diagnostic instrument of Supersonic Imagine (France) and an L15-4 linear array probe were used. The medial head of the quadriceps muscle was measured. The subjects wore short pants that settled above the knees. Tight pants were avoided to prevent impaired venous return, which can affect the power Doppler ultrasonography result. The subjects did not exercise within half an hour before testing. Two-dimensional images of the subjects' muscles were collected in a quiet resting state and used to measure muscle thickness and the average echo intensity. The power Doppler images were used to measure the level of muscle hyperemia. The measurements were performed in the 0° knee extension position and the most prominent part of the medial head of the quadriceps muscle was measured by the ultrasound physician using visualization. The probe angle was perpendicular to the trajectory of the muscle bundle, and the measurement was performed with the muscle in a relaxed state. After the measurements, the knee was restrained to complete the isokinetic muscle strength test. When testing of the last group was completed, the knee was released immediately. The two-dimensional image and the power Doppler image at the same location were captured and the image acquisition time was no more than 3 s.
Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.
The purpose of this study is to see why malaria epidemics occur in highland areas in Kenya. A better understanding of factors contributing to malaria may be necessary for malaria vaccine planning. These factors include interactions between age, where malaria is passed from mosquitoes to people, immune system (how the body fights infection) responses and other factors that contribute to malaria in epidemic-prone areas. About 6400 people from the villages of Kapsisiywa and Kipsamoite will participate. Study procedures will include in home surveys, which will involve a census and an interview by researchers. Blood samples and smears will be collected from some volunteers in both communities to understand how the body protects itself from malaria and to check for malaria parasites. Twice each month, random houses will be selected from 3 places in the village to measure the number of mosquitoes in the home. Participants may be involved in the study for up to 4 years.
A composition or pharmaceutical composition having a fullerene with a cage structure and an acid phosphonate group, in which phosphorous has an oxidation state of three (3). Also, a composition in which the acid phosphonate group is completely neutralized with an alkali neutralizer, including sodium or potassium. The fullerene includes C60 or C70 fullerene and the alkali neutralizer includes sodium or disodium, respectively. The composition formula is C60(O3PNa2)x, in which x includes disodium phosphonate groups with a hydrophobic region at unreacted carbons and with a hydrophilic region arising from the pendant phosphonate substituents. Each acid phosphonate groups is neutralized to form a sodium salt. One type of protic acid phosphonate ester is neutralized to form alkali-R functional groups. A number of disodium phosphonate groups for the composition is five (5) or ten (10) or fifteen (15) and the formula for the composition is C60(O3PNa2)5 or C60(O3PNa2)10 or C60(O3PNa2)15, respectively.
The lens worn first is a new etafilcon A toric contact lens and the lens worn second is a marketed etafilcon A toric contact lens. Each lens worn for a maximum of 15 minutes bilaterally.
Risk Summary

Based on data from animal reproductive toxicity studies, FILSPARI can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4)]. Available data from reports of pregnancy in clinical trials with FILSPARI are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sparsentan to pregnant rats throughout organogenesis at 10-times the maximum recommended human dose (MRHD) in mg/day caused teratogenic effects in rats, including craniofacial malformations, skeletal abnormalities, increased embryo-fetal lethality, and reduced fetal weights (see Data). Advise pregnant patients of the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In embryo-fetal development studies in pregnant rats and rabbits, teratogenicity and/or developmental toxicity were observed, which were attributed to the antagonism of endothelin type A (ETA) and angiotensin II type 1 (AT1) receptors.

In pregnant rats, oral administration of sparsentan throughout organogenesis at doses of 80, 160, and 240 mg/kg/day resulted in dose-dependent teratogenic effects in the form of craniofacial malformations, skeletal abnormalities, increased embryo-fetal lethality, and reduced fetal weights at all doses tested. The area under the curve (AUC) at the lowest dose tested (80 mg/kg/day) was approximately 10 times the AUC at the MRHD of 400 mg/day. In pregnant rabbits, oral administration of sparsentan throughout organogenesis at doses of 2.5, 10 and 40 mg/kg/day resulted in maternal death and abortions at 10 and 40 mg/kg/day which provided exposures approximately 0.1 times and 0.2 times the AUC at the MRHD, respectively. An increase in a fetal variation (supernumerary cervical ribs) occurred at the high dose of 40 mg/kg/day.

In the pre- and postnatal development study in rats, oral administration of sparsentan during pregnancy and the lactational period at doses of 5, 20, or 80 mg/kg/day resulted in maternal death, body weight loss/reduced body weight gain, and adverse clinical signs at 80 mg/kg/day. An increase in pup deaths occurred at 80 mg/kg/day (approximately 10 times the AUC at MRHD) during the neonatal period through weaning, and decreased growth occurred at ≥ 20 mg/kg/day (approximately 2.6 times the AUC at the MRHD) after weaning. The NOAEL for pre- and postnatal development in rats was 5 mg/kg/day, approximately 0.7 times the AUC at the MRHD.
Tamsulosin hydrochloride USP is an antagonist of alpha1A adrenoceptors in the prostate.

Tamsulosin hydrochloride USP is (-)-(R)-5-[2-[[2-( o-Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride USP is a white crystalline powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether. 

The molecular formula of tamsulosin hydrochloride USP is C 20H 28N 2O 5S • HCl. The molecular weight of tamsulosin hydrochloride USP is 444.98. Its structural formula is:   
  
Each tamsulosin hydrochloride capsule, USP for oral administration contains tamsulosin hydrochloride USP 0.4 mg, and the following inactive ingredients: polysorbate 80, methacrylic acid copolymer dispersion, triacetin, sodium lauryl sulfate, microcrystalline cellulose and calcium stearate. The capsule shells have the following inactive ingredients: FD & C Blue 2, iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide and gelatin. The black ink has the following inactive ingredients: shellac, propylene glycol, black iron oxide E172 and potassium hydroxide.   
USP dissolution test pending.