anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Lamotrigine extended-release tablets can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8% (8 per 1,000) in pediatric patients (aged 2 to 16 years) receiving immediate-release lamotrigine as adjunctive therapy for epilepsy and 0.3% (3 per 1,000) in adults on adjunctive therapy for epilepsy. In a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking adjunctive immediate-release lamotrigine, there was 1 rash-related death. Lamotrigine extended-release tablet is not approved for patients younger than 13 years. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate. 

The risk of serious rash caused by treatment with lamotrigine extended-release tablet is not expected to differ from that with immediate-release lamotrigine. However, the relatively limited treatment experience with lamotrigine extended-release tablets makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with lamotrigine extended-release tablets.

Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash caused by lamotrigine extended-release tablets. There are suggestions, yet to be proven, that the risk of rash may also be increased by (1) coadministration of lamotrigine extended-release tablets with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of lamotrigine extended-release tablets, or (3) exceeding the recommended dose escalation for lamotrigine extended-release tablets. However, cases have occurred in the absence of these factors.

Nearly all cases of life-threatening rashes caused by immediate-release lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.

Although benign rashes are also caused by lamotrigine extended-release tablets, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, lamotrigine extended-release tablets should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring [ see Warnings and Precautions (5.1)].
The present invention discloses aberrant expression products of the KLK4 gene, which segregate with at least one condition selected from a cancer or a benign tumour. The invention also discloses a method for detecting the presence or diagnosing the risk of said at least one condition by detecting aberrant KLK4 expression The invention also discloses isolated polynucleotides comprising a nucleotide sequence that corresponds or is complementary to at least a portion of an aberrant KLK4 polynucleotide, which correlates with the presence or risk of said at least one condition. Also disclosed are isolated polypeptides comprising an amino acid sequence that corresponds to at least a portion of an aberrant K4 polypeptide, which correlates with the presence or risk of said at least one condition. The invention also extends to variants and derivatives of these molecules, to vectors comprising aberrant KLK4 polynucleotides and to host cells containing such vectors. The invention further extends to antigen-binding molecules that are immuno-interactive with aberrant K4 polypeptides and to the use of these antigen-binding molecules, the aberrant KLK4 polynucleotides and aberrant K4 polypeptides in assays and kits for detecting the presence or diagnosing the risk of said at least one condition. The invention further encompasses the use of functional KLK4 polynucleotides or functional K4 polypeptides or agents that modulate the level and/or functional activity of an expression product of KLK4 or of a gene belonging to the same biosynthetic or regulatory pathway as KLK4 for treating and/or preventing one or more of said conditions.
The invention relates to the use of scutellarin and ramification thereof in preparing medicine for preventing or treating diseases relevant with hepatofibrosis or preventing or treating hepatofibrosis caused by various reasons and preventing or treating hepatofibrosis caused by chronic liver disease, belonging to the technical filed of medicine. The invention shows that the scutellarin and scutelloside have hepatofibrosis-resisting function by cytology experiment and animal experiment; and the scutellarin and the scutelloside can be prepared into various pharmaceutical preparations for preventing and treating the chronic liver disease and the hepatofibrosis. The invention also relates to a method for preparing micropill of the scutellarin and the ramification thereof. The micropill substantially comprises 50-300 of scutellarin and ramification thereof, 50-1800 of polymer material and 0-300 of insoluble material. The polymer material selects from acrylicresins or/and ethyl cellulose and the ramification thereof. The viscosity range of the ethyl cellulose is 3-110 mPa.s, preferably is 20-50 mPa.s, and the insoluble material preferably selects from the micropill of silica gel.
Subjects will be referred for non-invasive and/or invasive testing and evaluation. Prior to treatment of subjects considered for PCI and/or CABG, the investigator and the institution's heart team will review the results of all available diagnostic tests, including cCTA and FFRCT, and will recommend a treatment strategy accordingly. FFRCT is a non-invasive method to evaluate the hemodynamic significance of coronary artery lesions. FFRCT calculates FFR from subject-specific cCTA data using computational fluid dynamics under rest and simulated maximal coronary hyperemic conditions. FFRCT values range between 0 and 1, and values ≤0.80 are considered hemodynamically (HD)-significant.
Patients who present with STEMI-CS will undergo treatment with Impella, followed by PCI. Subjects are then immediately treated post-procedure with an infusion of SSO2 Therapy for a duration of 60 minutes.
Recent years have witnessed an increase in survival of very or extremely low birth weight infants, with a corresponding increase of attention to encephalopathy of prematurity (EOP) and the following neurological disorders. Studies suggested that hypoxic-ischemic injury and perinatal infection might be the two main risk factors of EOP, including white matter injury, neuronal-axonal diseases and cerebellar hemorrhage, which have a strong impact on neurological outcomes. Sequelae like cerebral palsy or mental retardation become a burden to both the family and society. Therefore, the risk factors of brain injury become the critical issue of both Obstetrics and Neonatology. More importantly, little is known about the morbidity of neurodevelopmental impairment and its risk factors in China. Thus, the aim of our study is to explore the perinatal risk factors of encephalopathy of prematurity and the morbidity of the following neurodevelopmental impairments in preterm infants with gestational age \<32 weeks in China.
Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.
Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout and is thought to act on urate transporter 1 (URAT1), a novel member of the organic anion transporter (OAT) family, thereby increasing uric acid excretion in the kidney by blocking urate reuptake, and then, resulting in a decrease of SUA.

Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Olmesartan is orally administered in the prodrug form, olmesartan medoxomil, which is converted to the pharmacologically-active compound olmesartan upon de-esterification by the enzyme arylesterase in the intestinal wall, portal blood, and liver. Olmesartan is excreted by hepatobiliary and renal systems without further metabolism, and its pharmacokinetic profile is not affected by age or gender. In addition, the pharmacokinetic and pharmacodynamic profile of olmesartan is favorable, both in terms of providing effective 24-hour blood pressure (BP) control with once-daily dosing, and in restricting the likelihood of pharmacokinetic interactions with other drugs. Studies in vitro show organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, multidrug resistance-associated protein 2 (MRP 2), and breast cancer resistance protein (BCRP) are involved in hepatobiliary and renal transport of olmesartan. We know probenecid interferes with the kidneys' organic anion transporter (OAT). Will probenecid have effects on the pharmacokinetics of olmesartan thereby result in changes of antihypertensive effect and side effects of olmesartan? Until now, many clinical studies have shown olmesartan has no pharmacokinetic interactions with other drugs; moreover, there is no research about the interactions between olmesartan and probenecid. In this study, we assess the involvement of probenecid in the pharmacokinetics and tolerability of olmesartan.
A system for electrostatically coating particles is provided. The system is particularly well suited for coating charged drug delivery particles (e.g., nanoparticles, microparticles) with a coating of opposite charge. The coating may include a targeting moiety such as a small molecule ligand, peptide, protein, aptamer, etc. The coated particles are biodegradable and/or biocompatible, have a near neutral zeta (ξ) potential, and are stable in serum. The invention also provides pharmaceutical compositions and kits including the inventive coated particles. Methods of preparing and using the inventive particles are also included.
Kounis syndrome (KS) was first described in 1991 by Kounis and Zavras and is also known as allergic angina syndrome or allergy myocardial infarction. It is a rare, and frequently undiagnosed syndrome that is characterized by an anaphylactic reaction. Allergens cause massive degranulation of mast cells leading to coronary spasm, microvascular angina, and/or endothelial dysfunction with myocardial infarction. The annual incidence of severe, life-threatening anaphylaxis with circulatory symptoms is about 7.9-9.6 cases per 100,000 people. More than 300 cases of KS have been described after exposure to various agents such as drugs, insect venoms, food, or medicated stents. Although the incidence of KS is very low, the incidence of myocardial infarction due to anaphylaxis secondary to gadolinium is even lower, reported in a range of 0.002-0.01%. The objective of this article is to review the current data on KS, regarding a case of allergy to gadolinium, which has an extremely low incidence.
As patients with sickle cell disease (SCD) age, recurrent vaso-occlusive episodes lead to progressive end-organ damage. Pulmonary hypertension (PHT) represents an example of such end-organ damage. Pulmonary hypertension, a common complication in patients with sickle cell disease (SCD), results in a shortened survival. The high mortality reported in SCD patients with PHT appears to occur particularly in those patients with moderate and severe elevations in their pulmonary artery pressure. The overall objective of this proposal is to evaluate the effect of chronic red blood cell transfusion on PHT in SCD. We hypothesize that by increasing the hemoglobin concentration and decreasing the amount of HbS, these patients would experience improvements in their PHT.

Thus, the specific aim of this clinical trial is to evaluate the effects of RBC transfusion on pulmonary hypertension in SCD, as well as the effect of chronic RBC transfusion on plasma markers of thrombin generation, platelet activation, and nitric oxide metabolites.

Study subjects will be transfused monthly for 6 months to investigate the safety and efficacy of RBC transfusion in SCD patients with PHT. All packed red blood cells will have extended antigen matching for C, D, E and Kell to minimize the risk of alloimmunization. Subjects will receive other routine treatments for SCD. Specific outcome variables will be evaluated at 1 month, 3 months, and 6 months. All study subjects will receive simple transfusion of packed red blood cell to achieve a post-transfusion hemoglobin (Hb) not greater than 10 g/dL. For those subjects who may have baseline hemoglobins in whom a post transfusion Hb would exceed 10 g/dL, they will require a limited exchange transfusion, i.e. phlebotomy of 1 unit of blood, followed by transfusion of 2 units of packed RBC. All study subjects will return for assessment of safety and/or efficacy measures every two weeks for the first month, and subsequently every four weeks till the completion of the study. Study subjects who experience a documented worsening of their disease (decreased SaO2, worsening 6-minute walk) on at least two consecutive follow up visits will be taken off the study. At the end of the study, subjects will have the option of continuing on chronic RBC transfusion.
Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis. A novel PVT model was developed via two-step total portal vein ligation in healthy and thioacetamide (TAA)-cirrhotic rats. Circulating and liver-infiltrating neutrophils were isolated from individuals with cirrhosis to examine neutrophil extracellular traps (NETs) and explore their unique characteristics and implications in PVT-associated fibrosis in cirrhosis. We further validated macrophage-myofibroblast transition (MMT) via multiplex immunofluorescence and single-cell sequencing. In the experimental model, cirrhosis promoted PVT development and portal vein intimal thickening. Interestingly, cirrhosis promoted spontaneous resolution of PVT due to instability of thrombus structure, along with pulmonary and intrahepatic clots. NETs-MMT mediate cirrhotic PVT and PVT-associated fibrosis, including fibrotic thrombus remodeling and increased hepatic collagen deposition. Mechanistically, caspase-4-dependent activation of neutrophils and GSDMD mediated the formation of NETs. The extracellular DNA of NETs promoted TGF-β1/Smad3-driven MMT. Inhibiting GSDMD with disulfiram suppressed cirrhotic PVT and prevented associated fibrosis. The cirrhotic PVT model reflected the following three main characteristics of cirrhotic PVT: spontaneous resolution, immunothrombosis, and intimal fibrosis. Targeting NETs with GSDMD inhibitors may serve as a new therapeutic concept to treat cirrhotic PVT.
Icotinib is administered orally three times per day. Radiation therapy (SRS/ WBRT/ HA-WBRT/SMART) start in 1 month since take icotinib orally.
Microparticulate carrier materials for a large and varied group of pharmaceutical and cosmetic agents are disclosed. Microdispersions of such carrier materials charged with at least one isomer or derivative of 2-amino-1-phenylpropanol are also described. The microdispersions can be formulated for oral, parenteral, topical, inhalation and suppository administration. The formulations have varied uses depending on the pharmaceutical and or cosmetic agent utilized. The microparticles are suitably charged particles of silica, alumina, boron, charcoal and the like and have a particle size of about 3 to about 250 μm. The pharmaceutical and cosmetic active materials complex with the microparticles. The liquid carrier for the microparticles include water, propylene glycol, alcohols such as methanol, ethanol and propanols, and dimethyl sulfoxide. The resulting dispersions are believed to be similar to isotonic saline and mimic body fluids which makes the dispersions very physiologically compatible thereby aiding and speeding the delivery of the agents across membranes and to the afflicted tissue. Methods of using these microdispersions and the containing the same are also disclosed.
BACKGROUND: Finding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown. Additionally, whether ginkgolic acid (GA), a SUMOylation inhibitor, inhibits hepatic fibrosis by inhibiting SUMO1-activating enzyme subunit 1 (SAE1) should be further investigated.
METHODS: Liver tissues of patients with hepatic cirrhosis and a rat model of hepatic fibrosis constructed with CCl4 (400 mg/kg, twice weekly) or TAA (200 mg/kg, twice weekly) were selected, and the degree of hepatic fibrosis was then evaluated using H&E, Sirius red, and Masson's trichrome staining. After knockdown or overexpression of SAE1 in hepatic stellate cells, the expression levels of ferroptosis and hepatic fibrosis markers were measured in vitro. After intervention with a ferroptosis inhibitor, the expression levels were again measured in vivo and in vitro.
RESULTS: We first demonstrated that SAE1 increased in patients with hepatic cirrhosis. Subsequently, testing of the rat hepatic fibrosis model confirmed that GA reduced the expression of SAE1 and improved hepatic fibrosis in rats. Then, we used hepatic stellate cell lines to confirm in vitro that GA inhibited SAE1 expression and induced ferroptosis, and that overexpression of SAE1 or inhibition of ferroptosis reversed this process. Finally, we confirmed in vivo that GA induced ferroptosis and alleviated the progression of hepatic fibrosis, while inhibiting ferroptosis also reversed the progression of hepatic fibrosis in rats.
CONCLUSION: SAE1 is a potential anti-fibrotic target protein, and GA induces ferroptosis of hepatic stellate cells by targeting SAE1 to exert an anti-hepatic fibrosis effect, which lays an experimental foundation for the future clinical application of its anti-hepatic fibrosis effect.
OBJECTIVES: The aim of this study was to investigate a panel of inflammatory biomarkers in plasma from forklift truck operators (FLTOs) and healthy controls, and their relation to neck pain characteristics.
METHODS: From employees in a warehouse, 26 FLTOs were recruited and 24 healthy age- and sex-matched controls (CONs) were recruited via advertisement. The inclusion criterion for FLTOs was that they should operate reach decker and/or counterbalanced tilting mast forklift trucks. All participants were asked to answer a questionnaire covering demographic data, pain intensity numeric rating scale (NRS), anatomical spread, psychological distress, and health aspects. Pain sensitivity was measured using a pressure algometer. Blood samples were collected and analyzed for inflammatory proteins in plasma using a panel of 71 cytokines and chemokines. Multivariate data analysis including orthogonal partial least square-discriminant analysis (OPLS-DA) was performed to identify significant biomarkers.
RESULTS: Thirty percent of FLTOs reported NRS > 3 in the neck. Shoulder pain was common in 26% of the FLTOs. Pain and discomfort that most often prevented completion of activities were in the neck (20%), lower back (32%), and hips (27%). The FLTOs reported significantly (p = 0.04) higher levels of anxiety than the CON group and they had significantly lower pressure pain thresholds in the trapezius muscle on both right (p < 0.001) and left sides (p = 0.003). A significant OPLS-DA model could discriminate FLTOs from CON based on nine inflammatory proteins where the expression levels of four proteins were upregulated and five proteins were downregulated in FLTOs compared to CONs. Twenty-nine proteins correlated multivariately with pain intensity.
CONCLUSIONS: The profile of self-reported health, pain intensity, sensitivity, and plasma biomarkers can discriminate FLTOs with pain from healthy subjects. A combination of both self-reported and objective biomarker measurements can be useful for better understanding the pathophysiological mechanisms underlying work-related neck and shoulder pain.
A 52-year-old woman was admitted with a primary complaint of abdominal distension and increased abdominal circumference for more than half a year. There was no evidence of infection or solid tumor on abdominocentesis or laparoscopic surgery. Concurrently, smoldering multiple myeloma was diagnosed. Due to refractory ascites and portal hypertension, a transjugular intrahepatic portosystemic shunt was performed, but the efficacy was not satisfactory. As the anemia progressed, she was finally diagnosed with active multiple myeloma after monoclonal plasma cells were detected in the ascites by flow cytometry. Treated with a triplet regimen that included bortezomib, cyclophosphamide, and dexamethasone (BCD), she achieved a very good partial response and ascites regressed.
Diabetic retinopathy is a leading cause of vision loss in Canada and creates significant economic and social burden on patients. Diabetic retinopathy is largely a preventable complication of diabetes mellitus. Yet, hundreds of thousands of Canadians continue to be at risk and thousands go on to develop vision loss and disability. Blindness has a significant impact on the Canadian economy, on families and the quality of life of affected individuals. This paper provides an economic analysis on two potential interventions for preventing blindness and concludes that use of AI to identify high-risk individuals could significantly decrease the costs of identifying, recalling, and screening patients at risk of vision loss, while achieving similar results as a full-fledged screening and recall program. We propose that minimal data interoperability between optometrists and family physicians combined with artificial intelligence to identify and screen those at highest risk of vision loss can lower the costs and increase the feasibility of screening and treating large numbers of patients at risk of going blind in Canada.