anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Coenzyme Q10 (or CoQ10) is a marketed supplement in US even though it can be synthesized in the body via complicated biochemical pathways. It exists in both reduced and oxidized states, namely ubiquinol and ubiquinone, respectively. It is commonly present in all cell membranes. The main function of CoQ10 is to participate in energy production. Further, the reduced form of CoQ10, ubiquinol, is appreciated as an important lipophilic antioxidant to protect free radical induced damages to DNA, lipid, and proteins. Given that older adults have increased production of free radicals, suboptimal antioxidant defenses toward free radicals, and a decreased capability to replenish utilized CoQ10, CoQ10 supplementation can be one of feasible ways to increase CoQ10 status in order adults. Most supplements available for consumers are in the oxidized form. While the ubiquinol form is also available, whether the reduced form will be more effective to replenish CoQ10 status in older subjects remains to be explored. Thus, investigators aimed to examine whether ubiquinol will be more effectively absorbed in older adults with a low antioxidant defense status. To pursue this aim, investigators will conduct a double blind, randomized, crossover design trail with 5 study visits (1 screening visit and 4 study visits). Ten older men (\>55 y, BMI: 25-5 kg/m2) with a compromised antioxidant defenses will be recruited and complete the trial. Eligible subjects will be randomized to receive 200 mg/d ubiquinol or ubiquinone for 2 weeks with 2-week washout between crossover. Ubiquinol and ubiquinone in plasma and immune cells in blood will be assessed to reveal whether the reduced form, ubiquinol, is more absorbable than the oxidized form, ubiquinone in older male adults.
Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. The antiarrhythmic actions of RN are mainly attributed to its ability to block INa, INaL, and the rapidly activating delayed rectifier potassium current (IKr).7 In experimental studies, RN proved very effective in suppressing late phase 3 early afterdepolarization and delayed afterdepolarization mediated triggered activity in pulmonary vein sleeves.8 RN was shown very effective in suppressing persistent, vagally mediated AF in animal models.9 Clinical evidence of an AF-suppressing effect of RN comes mainly from small caliber studies. Murdock et al, reported a high conversion rate (72%) after administration of 2,000 mg of RN (in a "pill-in-the-pocket" fashion) in patients with short lasting (\<48 hours) new onset paroxysmal AF.10 Our group demonstrated both the superior efficacy and the accelerated action of the combined therapy of Amiodarone with RN compared to Amiodarone alone in patients with paroxysmal AF. Notably, the efficacy benefit of this combination was more pronounced in patients with dilated left atria which is also more likely to occur in cases of persistent AF.11, 12 In a prospective, randomized, double-blind, placebo-control phase II study, different doses of RN were tested in the prevention of AF recurrence after successful electrical cardioversion. Despite the fact that the study did not reach its primary end-point since none of the individual doses of RN significantly delayed the time to first AF recurrence as compared with placebo, an antiarrhythmic efficacy for the two higher doses of RN (500 and 750mg bd) was strongly suggested. The same study confirmed the safety of RN with no evidence for proarrhythmia.13 Notably, beta-blockers were used in less than 50% of patients studied in this study.

Although the efficacy of beta-blockers in the maintenance of sinus rhythm is low, the addition of a beta-blocker to an antiarrhythmic agent that exerts its action by inhibiting inward Na+ current like RN and Flecainide may represent an interesting approach in preventing AF relapse. Various laboratory studies have demonstrated that inward Na+ current could be modulated by beta-adrenergic receptors in a variety of cell lines.14, 15 In this context, the beta-blocking activity of Amiodarone or Dronedarone may account for the successful combination with RN in suppressing AF in either experimental or clinical studies.
<P>PROBLEM TO BE SOLVED: To obtain a protein for forming a DnaJ-like domain to form a domain significant for analysis of a three-dimensional structure and its structural information.  <P>SOLUTION: (1) The protein comprises an amino acid sequence to form the DnaJ-like domain or its salt. (2) The protein comprises an amino acid sequence in which one or several amino acids are deleted, substituted or added in the amino acid sequence to form the DanJ-like domain and which has substantially the same function as that of the protein (1). The method for producing the protein or its salt is provided. The polynucleotide encodes the protein or its salt. The antibody against the protein, the screening method using the protein, and the screening method using the three-dimensional structure.  <P>COPYRIGHT: (C)2004,JPO
Painful vasoocclusive crisis (VOC) is the most frequent acute clinical manifestation of sickle cell disease (SCD), frequently necessitating emergency department visits and/or hospitalization. Approximately 10-30% of patients admitted to the hospital with a VOC will go on to develop acute chest syndrome (ACS), a complication of SCD resulting in significant morbidity and mortality. While ACS related mortality appears to be improving in the United States, the number of hospital admissions for ACS is on the rise. Unfortunately, the diagnosis of ACS is often delayed with up to 50% of cases diagnosed two to three days after an admission for VOC. The clinical diagnosis of ACS is often delayed as it mimics other respiratory diseases. Furthermore, the lack of definitive laboratory and radiological biomarkers further confounds the ability to detect rapidly progressive ACS, a phenotype accounting for considerable ACS-related mortality. Currently, a key criterion for the diagnosis of ACS is the presence of new airspace disease on a chest radiograph in a sickle cell patient with respiratory symptoms. However, the appearance of abnormalities on chest radiography (CXR) often lags behind clinical signs and diagnostic techniques such as computed tomography (CT) which tends to reveal radiologic changes much earlier than CXR. Early diagnosis and treatment of ACS improves outcomes, hence the scientific rationale to perform such studies and develop diagnostic algorithms to facilitate early detection of ACS.

In the current study proposal, we will utilize stored blood samples and review CT scans and CXRs from 65 participants of the DeNOVO trial (NHLBI protocol # 05-H-0019). This multicenter trial conducted between 2004-08 at 11 centers including the NIH, showed that among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution. In this study, patients enrolled at the NIH study site had baseline admission research blood drawn and thoracic CT scans performed. A repeat CT scan and repeat blood work was subsequently obtained during the development of ACS. The archived data from this subset of the study cohort therefore provides an opportunity to rigorously test the hypothesis that CT scans performed early in the setting of VOC in patients going on to develop ACS would have utility in the rapid diagnosis of this condition. Furthermore, the availability of stored plasma samples from this cohort permits the study of both imaging and plasma biomarkers in a prospectively defined sample of SCD patients. Specifically, we will identify patients admitted with VOC that went on to develop ACS and study their CT scans and plasma to determine whether these biomarkers will rapidly diagnose ACS. The patients in the same study who did not develop ACS will serve as controls.
This trial is designed single arm. All the subjects enrolled will receive the experimental intervention: ScTIL210 injection alone or with B lymphocytes adjuvant.
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remissions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveil¬lance" has manifestly failed in every cancer that is clinically apparent. It is the goal of this study to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an effective, self-sustaining immune response. It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA), which is prominently expressed on tumors of the stomach, colon and rectum, breast, pancreas and other sites.
Participants receive Sodium Chloride isotonic (9mg/mL) solution for injection administered intravenously once over 2 minutes approximately 20 minutes before end of procedure. Dosage is administered according to weight: 0.2 mL/kg.
Introduction: Diabetic neuropathies are the most prevalent chronic complications of diabetes, characterized by pain and substantial morbidity. Although many drugs have been approved for the treatment of this type of pain, including gabapentin, tramadol (TMD), and classical opioids, it is common to report short-term results or potentially severe side effects. TMD, recommended as a second-line treatment can lead to unwanted side effects. Cannabidiol (CBD) has been gaining attention recently due to its therapeutic properties, including pain management. This study aimed to characterize the pharmacological interaction between CBD and TMD over the mechanical allodynia associated with experimental diabetes using isobolographic analysis. Materials and Methods: After diabetes induction by streptozotocin (STZ), diabetic rats were systemically treated with CBD or TMD alone or in combination (doses calculated based on linear regression of effective dose 40% [ED40]) and had the mechanical threshold evaluated using the electronic Von Frey apparatus. Both experimental and theoretical additive ED40 values (Zmix and Zadd, respectively) were determined for the combination of CBD plus TMD in this model. Results: Acute treatment with CBD (3 or 10 mg/kg) or TMD (2.5, 5, 10, or 20 mg/kg) alone or in combination (0.38+1.65 or 1.14+4.95 mg/kg) significantly improved the mechanical allodynia in STZ-diabetic rats. Isobolographic analysis revealed that experimental ED40 of the combination (Zmix) was 1.9 mg/kg (95% confidence interval [CI]=1.2-2.9) and did not differ from the theoretical additive ED40 2.0 mg/kg (95% CI=1.5-2.8; Zadd), suggesting an additive antinociceptive effect in this model. Conclusions: Using an isobolographic analysis, these results provide evidence of additive pharmacological interaction between CBD and TMD over the neuropathic pain associated with experimental diabetes induced by STZ.
The efficacy of venlafaxine hydrochloride extended-release capsules as a treatment for Panic Disorder (PD) was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for PD, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg per day in one study (study 1) and 75 or 225 mg per day in the other study (study 2). 

Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two studies, venlafaxine hydrochloride extended-release capsules were statistically significantly more effective than placebo (for each fixed dose) on all three endpoints, but a dose-response relationship was not clearly established. 

Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies. 

In a longer term study (study 3), adult outpatients meeting DSM-IV criteria for PD who had responded during a 12-week open phase with venlafaxine hydrochloride extended-release capsules (75 to 225 mg per day) were randomly assigned to continue the same venlafaxine hydrochloride extended-release capsules dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions. Response during the open phase was defined as ≤ 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved). Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12-week open-label period, patients receiving continued venlafaxine hydrochloride extended-release capsules experienced a statistically significantly longer time to relapse.
Blood samples for cultures and Multiplex PCR will be collected before start the antibiotic therapy in patients with sepsis. Multiplex PCR will be immediately undertaken and its results will be reported to prompt medical researcher (6-12 hours).The medical researcher will change the antibiotic regimen (De-escalation) immediately as a result of Multiplex PCR.
Subjects will receive caffeine on day -1 and after randomization subject will either receive GSK598809 or Placebo on Day 1. After washout period of 1-week subject will either receive GSK598809 or Placebo for 28 days.
Use of a composition (A), containing a superantigen (I) as active ingredient and at least one carrier, for treatment of carcinoma of the bladder. ACTIVITY : Cytostatic. Transitional cell carcinoma (TCC) of the bladder was induced in female rats by transurethral instillation of N-methyl-N-nitrosourea (MNU), then animals with superficical TCC were treated by instillation of the staphylococcal superantigen B (SEB) (1 or 10 Microg/ml), 14 weeks after start of treatment with MNU, with 1 application per week for 6 weeks. Two days after the last treatment the bladders were removed for analysis. Only 3 of 14 test animals still had tumors, and all these were apoptotic. Extensive migration of immunologically active cells into the bladder wall and the periphery of the tumor was detected. MECHANISM OF ACTION : (I), which binds specifically to the Vbeta region of the T cell receptor, induces synthesis of cytokines (interferongamma , interleukins 1, 2 and 6, and tumor necrosis factor alpha ); stimulates sproduction of antibodies and causes apoptosis and necrosis of tumor cells. Peripheral blood mononuclear cells (PBMC) were incubated with SEB (1 Microg/ml) for 5-7 hours, then co-cultured with RT12 bladder cancer cells for 12 hours. The rate of apoptosis in treated cells was 419% of that observed when unstimulated PBMC were used.
Participants in this group will receive counseling about best MASLD clinical practices in accordance with AASLD and ACSM practice guidelines Because in-office hepatology counseling for lifestyle intervention occurs every 12-24 wks,standard counseling will occur at each in-person visit. Mediterranean-informed, hypocaloric dietary counseling will be provided by a study investigator, with specific instructions to limit carbohydrates and saturated fat and enrich dietary intake with high fiber and unsaturated fats. Physical activity goals of 150 min/wk. of moderate intensity of 75 min/wk. of vigorous intensity activity will be suggested. To reinforce this education and promote self-monitoring, participants in this group will also receive a digital scale and fitness activity tracker.
One week of oral risperidone dosage started at 2mg for the first day and then increased to 4mg. If no side effects are noted, participants are started on the long-acting risperidone. The usual dosage of long-acting risperidone in the study will be 25mg every 2 weeks for a total of 12 weeks. The medication will be administered intramuscularly via injection.
S100A8 (MRP8) and S100A9 (MRP14) are critical mediators of the inflammatory response; they are usually present as heterodimers because of the instability of homodimers. Studies have demonstrated that S100A8/A9 expression is significantly upregulated in several central nervous system (CNS) diseases. S100A8/A9 is actively released by neutrophils and monocytes; it plays a key role in regulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion during inflammation. Additionally, S100A8/A9 can be used as a diagnostic biomarker for several CNS diseases and as a predictor of therapeutic response to inflammation-related diseases. In this work, we reviewed our current understanding of S100A8/A9 overexpression in inflammation and its importance in the development and progression of CNS inflammatory diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and stroke, and the functional roles and therapeutic applications of S100A8/A9 in these diseases. Finally, we discussed the current barriers and future research directions of S100A8/A9 in CNS diseases.
Essential tremor (ET) affects millions of people. Although frontline treatment options (medication, deep brain stimulation, and focused ultrasound ablation) have provided significant relief, many patients are unsatisfied with the outcomes. Peripheral suppression techniques, such as injections of botulinum toxin or sensory electrical stimulation of muscles, are gaining popularity, but could be optimized if the muscles most responsible for a patient's tremor were identified. The purpose of this study was to quantify the relationship between the activity in various upper limb muscles and the resulting tremor in patients with ET. Surface electromyogram (sEMG) from the 15 major superficial muscles of the upper limb and displacement of the hand and upper limb joints were recorded from 22 persons with ET while they performed kinetic and postural tasks representative of activities of daily living. We calculated the peak coherence (frequency-dependent correlation) in the tremor band (4-8 Hz) between the sEMG of each muscle and the displacement in each major degree of freedom (DOF). Averaged across subjects with ET, the highest coherence was found between elbow flexors (particularly biceps brachii and brachioradialis) and the distal DOF (forearm, wrist, and hand motion), and between wrist extensors (extensor carpi radialis and ulnaris) and the same distal DOF. These coherence values represent the upper bound on the proportion of the tremor caused by each muscle. We conclude that, without further information, elbow flexors and wrist extensors should be among the first muscles considered for peripheral suppression techniques in persons with ET.NEW & NOTEWORTHY We characterized the relationships between activity in upper limb muscles and tremor in persons with essential tremor using coherence, which provides an upper bound on the proportion of the tremor due to each muscle. Averaged across subjects and various tasks, tremor in the hand and distal joints was most coherent with elbow flexors and wrist extensors. We conclude that, without further information, these muscle groups should be among the first considered for peripheral suppression techniques.
In a study of the safety and efficacy of pamidronate disodium 90 mg (2-hour infusion) vs Zometa 4 mg (15-minute infusion) in bone metastases patients with multiple myeloma or breast cancer, renal deterioration was defined as an increase in serum creatinine of 0.5 mg/dL for patients with normal baseline creatinine (<1.4 mg/dL) or an increase of 1.0 mg/dL for patients with an abnormal baseline creatinine (≥1.4 mg/dL). The following are data on the incidence of renal deterioration in patients in this trial. See table below. 

###  Post-Marketing Experience

The following adverse reactions have been reported during post-approval use of pamidronate disodium. Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported in post-marketing use: General: reactivation of Herpes simplex and Herpes zoster, influenza-like symptoms; CNS: confusion and visual hallucinations, sometimes in the presence of electrolyte imbalance; Skin: rash, pruritus; Special senses: conjunctivitis, orbital inflammation; Renal and urinary disorders: focal segmental glomerulosclerosis including the collapsing variant, nephrotic syndrome, renal tubular disorders (RTD), tubulointerstitial nephritis and glomerulonephropathies; Laboratory abnormalities: hyperkalemia, hypernatremia, hematuria. Rare instances of allergic manifestations have been reported, including hypotension, dyspnea, or angioedema, and, very rarely, anaphylactic shock. Pamidronate disodium for Injection USP is contraindicated in patients with clinically significant hypersensitivity to pamidronate disodium or other bisphosphonates (see CONTRAINDICATIONS). Respiratory, thoracic and mediastinal disorders: adult respiratory distress syndrome (ARDS), interstitial lung disease (ILD). Musculoskeletal and connective tissue disorders: severe and occasionally incapacitating bone, joint, and/or muscle pain. 

Cases of osteonecrosis (primarily involving the jaw) have been reported predominantly in cancer patients treated with intravenous bisphosphonates, including pamidronate disodium. Many of these patients were also receiving chemotherapy and corticosteroids which may be risk factors for ONJ. Data suggest a greater frequency of reports of ONJ in certain cancers, such as advanced breast cancer and multiple myeloma. The majority of the reported cases are in cancer patients following invasive dental procedures, such as tooth extraction. It is therefore prudent to avoid invasive dental procedures as recovery may be prolonged. (See PRECAUTIONS.) 

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, including pamidronate disodium. (See PRECAUTIONS.)