anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Multiple sclerosis (MS) is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying MS pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-1β1) with MS pathogenesis and progression. In the experimental autoimmune encephalomyelitis (EAE) model of MS, we demonstrate that Nrg-1β1 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during pre-symptomatic, onset and progressive course of the disease. We demonstrate that plasma levels of Nrg-1β1 are also significantly reduced in individuals with early MS and is positively associated with progression to relapsing-remitting MS. The functional impact of Nrg-1β1 downregulation preceded disease onset and progression, and its systemic restoration was sufficient to delay EAE symptoms and alleviate disease burden. Intriguingly, Nrg-1β1 therapy exhibited a desirable and extended therapeutic time window of efficacy when administered prophylactically, symptomatically, acutely or chronically. Using in vivo and in vitro assessments, we identified that Nrg-1β1 treatment mediates its beneficial effects in EAE by providing a more balanced immune response. Mechanistically, Nrg-1β1 moderated monocyte infiltration at the blood-central nervous system interface by attenuating chondroitin sulfate proteoglycans and matrix metalloproteinase-9. Moreover, Nrg-1β1 fostered a regulatory and reparative phenotype in macrophages, T helper type 1 (Th1) cells and microglia in the spinal cord lesions of EAE mice. Taken together, our new findings in MS and EAE have uncovered a novel regulatory role for Nrg-1β1 early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity.
Video 1 shows three cases of intraoperative rupture during aneurysm coiling. Management of intraoperative aneurysm rupture is reviewed in brief, including reversal of anticoagulation/antiplatelets, intracranial pressure control, and rapid balloon deployment for control across the aneurysm neck. However, in all three cases, contrast extravasation continues despite aneurysm coiling, reversal of anticoagulation, and maximizing medical management. This is presumed to occur when the neck of the aneurysm is the site of rupture. We review the use of a salvage technique that can be considered as a last-ditch maneuver in these scenarios, which is deployment of Onyx liquid embolic (Medtronic). Onyx is the preferred liquid embolic for this use as it is cohesive instead of adhesive. The solvent used with Onyx, dimethyl sulfoxide, is also compatible with standard balloons.1 This is relevant because a balloon is needed both for control of hemorrhage during salvage embolization and for protection of the parent vessel from the embolic material. neurintsurg;16/12/1211/V1F1V1Video 1Demonstrating the technique of Onyx embolization for salvage hemostasis after intraoperative aneurysm rupture during coiling. Three example cases are shown.
The invention belongs to the field of traditional Chinese medicine development, and relates to a prescription medicine product. The invention aims to provide a prescription medicament which is mainly prepared from an extracted substance of a unique traditional Chinese medicine wild hibiscus and has a compatible formula. The composition medicine is different from the preparation mode of the traditional Chinese medicine new formulation medicine, changes the natural component proportion in the original traditional Chinese medicine through the composition, further stabilizes the activity of the original traditional Chinese medicine or a simple extract, and improves and strengthens the curative effect of the original inherent or certain extract of the wild hibiscus. The new medicine is approved or developed based on the approval. The scheme and the data of the invention save time in the process of administratively declaring new drugs, save expenses in experiments and can be used in clinic within ideal time. The implementation of the invention will form an industry with considerable scale benefits.
Emerging evidence suggests that inflammation mediated by the pannexin1 channel contributes significantly to acute ischemic stroke. It is believed that the pannexin1 channel is key in initiating central system inflammation during the early stages of acute ischemic stroke. Moreover, the pannexin1 channel is involved in the inflammatory cascade to maintain the inflammation levels. Specifically, the interaction of pannexin1 channels with ATP-sensitive P2X7 purinoceptors or promotion of potassium efflux mediates the activation of the NLRP3 inflammasome, triggering the release of pro-inflammatory factors such as IL-1 and IL-18, exacerbating and sustaining inflammation of brain. Also, increased release of ATP induced by cerebrovascular injury activates pannexin1 in vascular endothelial cells. This signal directs peripheral leukocytes to migrate into ischemic brain tissue, leading to an expansion of the inflammatory zone. Intervention strategies targeting pannexin1 channels may greatly alleviate inflammation after acute ischemic stroke to improve this patient population's clinical outcomes. In this review, we sought to summarize relevant studies on inflammation mediated by the pannexin1 channel in acute ischemic stroke and discussed the possibility of using brain organoid-on-a-chip technology to screen miRNAs that exclusively target the pannexin1 channel to provide new therapeutic measures for targeted regulation of pannexin1 channel to reduce inflammation in acute ischemic stroke.
The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including sertraline, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of sertraline with MAOIs intended to treat psychiatric disorders is contraindicated. Sertraline should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking sertraline. Sertraline should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of sertraline with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with sertraline and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
The invention relates to (a) streptonigrin monoxime, its mono-alkyl and trimethyl ester and the dimethylsulphate quaternary salt of the trimethyl ester, (b) isopropylidene azastreptonigrin, its mono-alkyl and trimethyl ester and the dimethylsulphate quaternary salt of the trimethylester, (c) dihydroazastreptonigrin, (d) azastreptonigrin and complexes of (a), (b), (c) and (d) with polyvalent metal ions, e.g. Ca, Cd, Ce, Cr, Cu, Fe, Ni and Zn.  Streptonigrin monoxime is obtained by reacting streptonigrin with hydroxylamine in a solvent such as pyridine.  Monoalkyl esters are produced by reacting the oxime with an alcohol and an acid catalyst especially a Lewis acid. The trimethyl ester is produced by reaction with diazomethane. The dimethylsulphate quaternary ammonium salt of the trimethyl ester is produced by treating the oxime with dimethylsulphate and K2CO3 in acetone solution.  Isopropylidene azastreptonigrin is prepared by treating dihydroazastreptonigrin with acetone in the presence of air oxidation.  Catalyctic or chemical reduction of the monoxime produces the unstable dihydroazastreptonigrin which oxidizes in air or oxygen to azastreptonigrin.  Streptonigrin has the formula <FORM:1043858/C2/1> Streptonigrin monoxime has the formula <FORM:1043858/C2/2> wherein X is the C and D rings above.ALSO:A pharmaceutical composition for the treatment of tumours in man and animals comprises streptonigrin monoxime or isopropylindene azastreptonigrin (antibiotics) and a carrier for oral or parenteral use.  Optional ingredients are other antibiotics, hypnotics, analgesics, local anaesthetics and carcinostatic agents e.g. nitrogen mustard type 6-mercaptopurine, 8-azaguanine, urethane, 6-diazo-5-oxo-1-norleucine, azaserine, triethylenemelamine mitomycin C, triethylenephosphoramide, 1, 4-dimethyl-sulphonyloxybutane and carcinostatic folic acid analogues.
BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time.
METHODS: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios.
FINDINGS: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable.
INTERPRETATION: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions.
FUNDING: Bill and Melinda Gates Foundation and Queensland Health.
NEW MATERIAL:The growth hormone polypeptide for fish, having the peptide sequence of formula. USE:Fish-growth promoting agent for pisciculture. PREPARATION:For example, the pituitary gland of Oncorhynchus keta is disinte grated and solubilized in a solution containing guanidium thiocyanate, and added to an EDTA solution. The mixture is centrifuged to recover the LRNA as a precipitate, which is dissolved in a concentrated solution of NaCl, etc., and passed through a column of oligo(dT)cellulose to obtain an mRNA having poly(A). A cyclic cDNA is synthesized from the mRNA, a vector primer and a linker DNA, and Escherichia coli is transformed with the cDNA to obtain a mutant containing a recombinant DNA integrated with a DNA coding the fish growth hormone. The mutant is cultured in a nutrient medium to obtain the objective polypeptide having the structure of formula.
Hypersensitivity reactions, including anaphylaxis, have been reported in association with tocilizumab products [see Adverse Reactions (6)] and anaphylactic events with a fatal outcome have been reported with intravenous infusion of tocilizumab products. Anaphylaxis and other hypersensitivity reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of patients in the 6-month controlled trials of intravenous tocilizumab and 0.2% (8 out of 4009) of patients in the intravenous all-exposure RA population. In the SJIA controlled trial with intravenous tocilizumab, 1 out of 112 patients (0.9%) experienced hypersensitivity reactions that required treatment discontinuation. In the PJIA controlled trial with intravenous tocilizumab 0 out of 188 patients (0%) in the tocilizumab all-exposure population experienced hypersensitivity reactions that required treatment discontinuation. Reactions that required treatment discontinuation included generalized erythema, rash, and urticaria. 

In the postmarketing setting, events of hypersensitivity reactions, including anaphylaxis and death have occurred in patients treated with a range of doses of intravenous tocilizumab products, with or without concomitant therapies. Events have occurred in patients who received premedication. Hypersensitivity, including anaphylaxis events, have occurred both with and without previous hypersensitivity reactions and as early as the first infusion of tocilizumab products .In addition, serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with tocilizumab products. 

TOFIDENCE for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. If a hypersensitivity reaction occurs immediately discontinue TOFIDENCE; treat promptly and monitor until signs and symptoms resolve.
Pentazocine hydrochloride and acetaminophen tablets are an analgesic possessing antipyretic actions.

Pentazocine is an analgesic with agonist/antagonist action which when administered orally is approximately equivalent on a mg for mg basis in analgesic effect to codeine.

Acetaminophen is an analgesic and antipyretic.

Onset of significant analgesia with pentazocine usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine, meperidine, and phenazocine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has a sedative activity.

Pentazocine is well absorbed from the gastrointestinal tract. Plasma levels closely correspond to the onset, duration, and intensity of analgesia. The time to mean peak concentration in 24 normal volunteers was 1.7 hours (range 0.5 to 4 hours) after oral administration and the mean plasma elimination half-life was 3.6 hours (range 1.5 to 10 hours).

The action of pentazocine is terminated for the most part by biotransformation in the liver with some free pentazocine excreted in the urine. The products of the oxidation of the terminal methyl groups and glucuronide conjugates are excreted by the kidney. Elimination of approximately 60% of the total dose occurs within 24 hours. Pentazocine passes the placental barrier.

Onset of significant analgesic and antipyretic activity of acetaminophen when administered orally occurs within 30 minutes and is maximal at approximately 21/2 hours. The pharmacological mode of action of acetaminophen is unknown at this time.

Acetaminophen is rapidly and almost completely absorbed from the gastrointestinal tract. In 24 normal volunteers the mean time to peak plasma concentration was 1 hour (range 0.25 to 3 hours) after oral administration and the mean plasma elimination half-life was 2.8 hours (range 2 to 4 hours).

The effect of pentazocine on acetaminophen plasma protein binding or vice versa has not been established. For acetaminophen there is little or no plasma protein binding at normal therapeutic doses. When toxic doses of acetaminophen are ingested and drug plasma levels exceed 90 mcg/mL, plasma binding may vary from 8% to 43%.

Acetaminophen is conjugated in the liver with glucuronic acid and to a lesser extent with sulfuric acid. Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged. The drug is also conjugated to a lesser extent with cysteine and additionally metabolized by hydroxylation.

If pentazocine hydrochloride and acetaminophen tablets are taken every 4 hours over an extended period of time, accumulation of pentazocine and to a lesser extent, acetaminophen, may occur.
This is a randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r) versus lpv/rtv in treatment-naive HIV-1 infected patients. Six hundred sixty treatment-naïve HIV-1 infected patients will be randomized in a 1:1 ratio to either 800/100 mg of TMC114/r once daily, or a total daily dose of 800/200 mg of lpv/rtv. All patients will take TMC114/r or lpv/rtv in combination with an NRTI background of Truvada (a combination pill of tenofovir and emtricitabine, "TDF/FTC"). The trial will consist of a screening period of approximately 14 to 28 days and a 96-week treatment period, followed by a 4-week follow-up period. The anti HIV-1 therapy initiated at baseline cannot be changed until the end of the treatment period. After the end of the treatment period (maximum of 96 weeks), patients will be followed for an additional 4 weeks to follow-up on any adverse events or laboratory abnormalities until resolution. Patients who fail either virologically or due to intolerance from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.

The primary efficacy parameter is virologic response defined as a confirmed viral load \< 50 copies/mL at Week 48 the objective of this study is to establish non-inferiority of TMC114/r versus lpv/rtv in terms of virologic response at Week 48 using a non-inferiority margin of 12%. To test this hypothesis, a two-sided 95% confidence interval (CI) of the difference in response rate between TMC114/r and lpv/rtv will be derived: If the lower bound of the CI exceeds -12%, non-inferiority will be concluded. Patients will take oral doses for up to 96 weeks of either 800/100mg of TMC114/r 1x/day or 800/200mg of lpv/rtv once daily, each in combination with TDF/FTC. (The 400/100 mg 2x/day dose of lpv/rtv will be used where the 1x/day use of lpv/rtv is not approved).
Methods are disclosed herein for increasing the number of stem cells or precursor cells. The number of stem cells can be increased by increasing survival and/or cell proliferation of the cells. The methods include contacting the cells with an effective amount of a Notch ligand, an effective amount of a growth factor, and an effective amount of angiopoietin-2 (Ang-2). In several embodiments, the methods include contacting the cells with an effective amount of a Jak inhibitor. In several non-limiting examples, the growth factor is insulin or glial derived neurotrophic factor (GDNF), or a combination thereof. In additional non-limiting examples, the Notch ligand is Delta. The cells can be in vivo orin vitro. Methods are also disclosed here for the treatment of a neurodegenerative disorder or spinal cord injury in a subject. In several non-limiting examples, the subject has Parkinson's disease or Alzheimer's disease.
There is no known antidote for EMTRIVA. Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology study single doses of emtricitabine 1200 mg were administered to 11 patients. No severe adverse reactions were reported.

The effects of higher doses are not known. If overdose occurs the patient should be monitored for signs of toxicity, and standard supportive treatment applied as necessary.

Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
Patients will be recruited who were diagnosed with adolescent idiopathic scoliosis prior to age 18 and before 1994 (minimum 20 year outcomes) with available xrays. Patients will be included who were treated with surgery, observation, or bracing. Patients will return for a one-time visit for new xrays, physical exam, health-related quality of life surveys, and pulmonary function testing.
The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents. Despite its key role in innate immunity, pyrin has also garnered significant attention due to its association with a range of autoinflammatory diseases (AIDs) including familial Mediterranean fever caused by disruption of the MEFV gene, or in other genes involved in its complex regulation mechanisms. Pyrin activation is strictly dependent on homeostasis-altering molecular processes, mostly consisting of the disruption of the small Ras Homolog Family Member A (RhoA) GTPases by pathogen toxins. The downstream pathways are regulated by the phosphorylation of specific pyrin residues by the kinases PKN1/2 and the binding of the chaperone 14-3-3. Furthermore, a key role in pyrin activation is played by the cytoskeleton and gasdermin D, which is responsible for membrane pores in the context of pyroptosis. In addition, recent evidence has highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The aim of this article is to offer a comprehensive overview of the most recent evidence on the pyrin inflammasome and its molecular pathways to better understand the pathogenesis behind the significant group of pyrin-related AIDs.
Autologous Bone Marrow fucosylated mesenchymal stem cells will be infused intravenously on Day 0. The first four patients enrolled will receive a single dose of 2 million cells/Kg and the last six patients enrolled, will receive a single dose of 5 million cells/kg.