anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The recommended dosage of ARAVA is 20 mg once daily. Treatment may be initiated with or without a loading dose, depending upon the patient's risk of ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression. The loading dose provides steady-state concentrations more rapidly. 

  * For patients who are at low risk for ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression, the recommended ARAVA loading dose is 100 mg once daily for 3 days. Subsequently administer 20 mg once daily. 
  * For patients at high risk for ARAVA-associated hepatotoxicity (e.g., those taking concomitant methotrexate) or ARAVA-associated myelosuppression (e.g., patients taking concomitant immunosuppressants), the recommended ARAVA dosage is 20 mg once daily without a loading dose [see Warnings and Precautions (5.2, 5.4)].



The maximum recommended daily dose is 20 mg once per day. Consider dosage reduction to 10 mg once daily for patients who are not able to tolerate 20 mg daily (i.e., for patients who experience any adverse events listed in Table 1). 

Monitor patients carefully after dosage reduction and after stopping therapy with ARAVA, since the active metabolite of leflunomide, teriflunomide, is slowly eliminated from the plasma [see Clinical Pharmacology (12.3)]. After stopping ARAVA treatment, an accelerated drug elimination procedure is recommended to reduce the plasma concentrations of the active metabolite, teriflunomide [see Warnings and Precautions (5.3)]. Without use of an accelerated drug elimination procedure, it may take up to 2 years to reach undetectable plasma teriflunomide concentrations after stopping ARAVA [see Clinical Pharmacology (12.3)].
This invention discloses immunopotentiating agents which stimulate an immune response. These agents are categorized into single agents that act directly, adjuvants added concurrently with the agents, or heteroconjugates. Heteroconjugate agents elicit or enhance a cellular or humoral immune response which may be specific for an epitope contained within an amino acid sequence. Enhanced hematopoieses by bone marrow stem cell recruitment was also a result of administering some of these agents. Examples of immunopotentiating agents include monoclonal antibodies and proteins derived from microorganisms (e.g., enterotoxins) which activate T cells. One method of treatment disclosed uses only the immunopotentiating agent to stimulate the immune system. Another uses adjuvants in combination with the agent. A third method employs heteroconjugates. Heteroconjugates comprise: (a) an immunopotentiating protein which is characterized as having an ability to stimulate T cells; and (b) a second protein having an amino acid sequence which includes an epitope against which a cellular or humoral response is desired. This invention also relates to a method of preparing the heteroconjugate, and to a method of stimulating the immune system in vivo in a novel way. One route of stimulation is to activate T cells, in some instances, specific subsets of T cells, by administering heteroconjugates containing an immunopotentiating protein and a second protein, to mammals. For this method of treatment, the second protein in the heteroconjugate is derived from abnormal or diseased tissue, or from an infectious agent; alternatively, the second protein is produced synthetically by standard methods of molecular biology. Sources of the second protein include tumors, viruses, bacteria, fungi, protozoal or metozoal parasites. Monoclonal antibodies or T cells prepared from mammals whose immune systems have responded to administration of the heteroconjugate may be produced and administered to induce passive immunity. A method of preparing a hybridoma which secretes said monoclonal antibodies and use of these monoclonal antibodies and T cells, are also disclosed. This invention is also directed to a vaccine comprising the heteroconjugate.
Organ transplantation is currently considered the treatment of choice for patients with end-stage renal disease (ESRD), an underestimated but increasing global burden. While there is an urgent need by the transplantation society and regulatory bodies to improve risk stratification of patients, there is no risk stratification system that adequately predicts the individual risk of allograft loss in transplanted patients. Currently, this represents a limitation to improve patient management and to define early surrogate endpoints for clinical trials and drug development. The inventors now report the development and validation of a comprehensive risk prediction score for predicting the survival of allogeneic kidney transplantation in individual patients (NCT 03474003). The iBox risk prediction score is the first integrated system to be validated in multiple independent populations in europe and north america and 3 clinical trials covering different clinical scenarios (NCT01079143, EudraCT2007-003213-13, NCT 01873157). In particular, iBox risk prediction scores offer the advantages of i) improved discrimination performance by combining traditional prognostic factors with mechanical notification parameters, ii) superior performance compared to existing scoring systems, iii) universality in assessment in geographically diverse cohorts from europe and north america, iv) transportability at different assessment times post-transplant, v) performance in various clinical scenarios including clinical trials, and vi) ease of access by clinicians and patients through online tools for patient risk calculation. Accordingly, the present invention relates to a method of predicting whether a renal transplant recipient is at risk for allograft loss by achieving an iBox risk prediction score.
Postoperative muscle loss is common in patients with bone metastases undergoing lower limb bone cancer curettage, affecting both limb skeletal and swallowing-related muscles, with rectus femoris thickness measured via ultrasound on postoperative day seven. Branched-chain amino acids (BCAAs) are crucial for muscle protein synthesis, but limited research exists on whether postoperative oral BCAA supplementation can reduce muscle loss, swallowing function deterioration, and short-term complications within three months. This study aims to determine if BCAA administration from postoperative day one to day 30 can reduce muscle loss, with rectus femoris thickness on day seven as the primary endpoint, while also exploring the effect on swallowing function, pharyngeal muscle strength, and complication rates. It will target patients with lower limb bone metastases from breast, lung, and prostate cancers, excluding those with high mortality risk or metastases in other regions. In a one-year randomized controlled trial, 40 patients will be assigned to receive either 3160 mg of daily BCAA for 30 days or no supplementation. Primary outcomes include rectus femoris muscle thickness and swallowing muscle strength assessed by high-resolution manometry, with postoperative complications followed for three months. The expected result is that the BCAA group will experience less muscle loss, greater rectus femoris thickness, reduced swallowing muscle decline, and fewer complications. This study aims to improve care quality, promote recovery, and support sustainable health goals.
Cognitive impairment is a decline in people's ability to think, learn, and remember, and so forth. Cognitive impairment is a global health challenge that affects the quality of life of thousands of people. The condition covers a wide range from mild cognitive impairment to severe dementia, which includes Alzheimer's disease (AD) and Parkinson's disease (PD), among others. While the etiology of cognitive impairment is diverse, the role of chemokines is increasingly evident, especially in the presence of chronic inflammation and neuroinflammation. Although inflammatory chemokines have been linked to cognitive impairment, cognitive impairment is usually multifactorial. Researchers are exploring the role of chemokines and other inflammatory mediators in cognitive dysfunction and trying to develop therapeutic strategies to mitigate their effects. The pathogenesis of cognitive disorders is very complex, their underlying causative mechanisms have not been clarified, and their treatment is always one of the challenges in the field of medicine. Therefore, exploring its pathogenesis and treatment has important socioeconomic value. Chemokines are a growing family of structurally and functionally related small (8-10 kDa) proteins, and there is growing evidence that pro-inflammatory chemokines are associated with many neurobiological processes that may be relevant to neurological disorders beyond their classical chemotactic function and play a crucial role in the pathogenesis and progression of cognitive disorders. In this paper, we review the roles and regulatory mechanisms of pro-inflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CCL11, CCL20, and CXCL8) in cognitive impairment. We also discuss the intrinsic relationship between the two, hoping to provide some valuable references for the treatment of cognitive impairment.
Juvenile systemic lupus erythematosus (jSLE) is a chronic multisystem inflammatory disease that manifests before the age of 16 years, following a remitting - relapsing course. The clinical presentation in children is multifaceted, most commonly including constitutional, hematological, cutaneous, renal, and neuropsychiatric symptoms. Neuropsychiatric manifestations range widely, affecting approximately 14-95 % of jSLE patients. They are associated with high morbidity and mortality, particularly at a younger age. Headaches, seizures, cognitive dysfunction, and mood disorders are the most frequent neuropsychiatric manifestations. The pathophysiological mechanism is quite complex and has not yet been fully investigated, with autoantibodies being the focus of research. The diagnosis of neuropsychiatric jSLE remains challenging and exclusionary. In this article we review the clinical neuropsychiatric manifestations associated with jSLE with the aim that early diagnosis and prompt treatment is achieved in children and adolescents with the disease.
The SBT group will receive a 4-week split-belt treadmill training program consisting of 3 training sessions every week. The training will have a progression of training duration over the four weeks. Participants will start at a total training duration of 30 minutes and this will be increased with 5 minutes every week. The maximal length will be 45 minutes of training. One session including breaks will take approximately 1 hour.
In recent years, the contribution of adipose tissue to obesity-related insulin resistance (IR), diabetes mellitus and cardiovascular disease (CVD) has become clear.In particular, accumulation of damaged cells in obese and aging adipose tissue has been shown to impair adipose tissue function and may thus increase CVD risk. Cellular and molecular alterations in adipose tissue are known to contribute to adipose tissue and systemic insulin resistance, chronic inflammation, and may lead to higher blood pressure. Importantly, any clinical consequences of adipose tissue dysfunction would be compounded by the large amount, and central metabolic role, of adipose tissue in humans. However, there is a gap in our understanding of the OSA-induced changes in the adipose tissue and its implication for development of cardiometabolic disorders.

The aim of this study is to examine the cellular and molecular composition of adipose tissue in obstructive sleep apnea (OSA) subjects in comparison to adipose tissue from healthy individuals. We hypothesize that adipose tissue from OSA subjects will have a higher accumulation of markers of cellular damage with positive p16 and γH2AX. These studies will provide pivotal insights into pathways that may be targeted to reduce cardiometabolic burden in OSA population.
The clinicians (PV and CM) used Carbide burs (330-010 Komet, Brasseler GmbH Co. Postfach 160.32631, Lemgo, Germany) to explore the defective margin, carious lesion or anatomic form of the restorations. Part of the restorative material adjacent to the defect was removed as an exploratory proceedure thus allowing a proper evaluation and subsequent diagnosis of the extent of the defect. Provided that the defect was limited and localized, the clinician then removed any defective tooth tissue. Mechanical retention was employed inside the existing AM restoration. Rubber dam isolation was used for this procedure. Repair of the restorations was carried out with a dispersed-phased amalgam (Original D, Wyckle Research Inc, Carson City, NV, USA).
The METH and/or cocaine dependent group were also enrolled in CTN0031 (NCT00573183) and seeking treatment. This group will be analyzed based on whether or not they completed treatment as defined by the study.
INTRODUCTION: Intramedullary spinal cord abscesses (ISCA) are rare and caused by central nervous system infections. Although polymicrobial infections are rarely seen in ISCAs, isolation of the causative pathogen is important for treatment. Here, we describe a very rare case of ISCA resulting from a mixed Streptococcus and Actinomyces infection.
CASE PRESENTATION: An 82-year-old man presented with acute posterior cervical pain and progressive quadriplegia. Radiological investigations revealed a mass lesion showing marginal enhancement at the level of the C3-4 vertebrae. Microsurgical drainage was performed, and Streptococcus and Actinomyces were identified as causative agents. Subsequent antibiotic treatment was noted to be beneficial to the patient.
DISCUSSION: This case suggests that mixed infection can develop into ISCA depending on the causative agents such as Actinomyces. Prompt pathogen-directed antibacterial therapy is required for ISCA treatment.
The present invention relates to peptides derived from human HMG‑CoA reductase, of general formula (I): R 1 -(AA) n -X1-Gly-Lys-Xl-(AA) P -R 2 , and of sequence SEQ ID No. 1 to SEQ ID No. 10. The present invention also relates to a cosmetic or pharmaceutical composition comprising at least one peptide of general formula (I), in a physiologically suitable medium. The present invention also relates to the use of this novel peptide, as an active principle that activates human HMG-CoA reductase, in a cosmetic composition intended to reinforce the barrier function of the skin and to stimulate epidermal differentiation. The invention also relates to a cosmetic treatment process intended to prevent and/or combat outside attacks and the signs of skin ageing.
Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape (Brassica napus) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum. A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana. Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis-acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35/AtGLR2.5 positively, while BnGLR12/AtGLR1.2 and BnGLR53/AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum, indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs.
A novel combination of a biocide (Glutaraldehyde or OPA), a surfactant, alcohol, and functional excipients for the oil and gas recovery industry. The surfactant is preferably a dual chain quaternary ammonium compound consisting of a mixture of alkyl dimethy-benzylammonium chlorides and alkyl dimethylethylbenzylammonium, that absorbs onto a surface and alters the free energy of that surface. The alcohol is preferably isopropyl alcohol. The functional excipients for the oil and gas recovery industry are a cellulose type proppant, a poloxamer wetting agent, a friction-reducing pluronic block copolymer, a drag reducing agent such as polethylene oxide, and a flocculating agent. The biocide may be OPA of the dialdehyde C 6 H 4 (CHO) 2  form, or Glutaraldehyde of formula C 5 H 8 O 2 . Both will produce an inherent bacteriostatic effect and lower surface tension and thus aids in the spread of the dual quat on the biofilm covered surface where it is readily absorbed by the negative surfaces of proteins and bacteria. It thus serves as a binding agent between the dual quat and the application surface. This multi purpose component helps create the unique aspect of the formulation. The foregoing constituents are combined in preferred concentrations within acceptable ranges to provide a synergistic formulation that combines biocidal molecules in a biological chemical system that actively transports itself into the cells, through biofilm and cell wall/membranes, thereby overcoming penetration restraints to improve kill and kill time, without the need for activation or any time or temperature control. This is an effective example of synergistic complementarity.
Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.
No data are available regarding overdosage in humans. Should accidental ocular overdosage occur, flush eye(s) with water or normal saline. If accidentally ingested, efforts to decrease further absorption may be appropriate (gastric lavage).

The most common signs and symptoms to be expected with overdosage with administration of a systemic beta-adrenergic blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. Should these symptoms occur, discontinue levobunolol therapy and initiate appropriate supportive therapy. The following supportive measures should be considered:

1\. Symptomatic bradycardia: Use atropine sulfate intravenously in a dosage of 0.25 mg to 2 mg to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride should be administered cautiously. In refractory cases the use of a transvenous cardiac pacemaker should be considered.

2\. Hypotension: Use sympathomimetic pressor drug therapy, such as dopamine, dobutamine or levarterenol. In refractory cases, the use of glucagon hydrochloride may be useful.

3\. Bronchospasm: Use isoproterenol hydrochloride. Additional therapy with aminophylline may be considered.

4\. Acute cardiac failure: Conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases the use of intravenous aminophylline is suggested. This may be followed, if necessary, by glucagon hydrochloride which may be useful.

5\. Heart block (second or third degree): Use isoproterenol hydrochloride or a transvenous cardiac pacemaker.
In the placebo-controlled trials, testosterone was increased in a dose related manner in SLE patients receiving prasterone. 

Prasterone caused an increased number of patients (in comparison to placebo) to have a decrease in serum complement (C3). The decrease in C3 was not associated with renal dysfunction. The medical literature suggests that a decline in serum complement may be a direct effect of suppression of complement production by androgens. 

The clinical studies suggest that administration of prasterone causes an early, but not progressive, decrease in serum lipids, primarily HDL-C and triglycerides. It would be prudent to follow NCEP guidelines while monitoring lipids in patients receiving prasterone. 

There were no changes of potential significance in liver function tests (ALT, AST, alkaline phosphatase, or total bilirubin) within and between the treatment groups. Equally, serum calcium, phosphorus, uric acid, total protein and albumin showed no clinically relevant differences. 

Mean 24-hour urine protein excretion was slightly higher in the prasterone group viz placebo. 

There does not appear to be a difference between placebo and prasterone for new hematuria accompanied by SLE renal involvement, as manifested by changes in urinary protein excretion, increased creatinine, or new therapy for renal SLE.