anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Methionine aminopeptidase type 2 (METAP2) is a ubiquitous, evolutionarily conserved metalloprotease fundamental to protein biosynthesis which catalyzes removal of the N-terminal methionine residue from nascent polypeptides. METAP2 is an attractive target for cancer therapeutics based upon its over-expression in multiple human cancers, the importance of METAP2-specific substrates whose biological activity may be altered following METAP2 inhibition, and additionally, that METAP2 was identified as the target for the anti-angiogenic natural product, fumagillin. Irreversible inhibition of METAP2 using fumagillin analogues has established the anti-angiogenic and anti-tumor characteristics of these derivatives; however, their full clinical potential has not been realized due to a combination of poor drug-like properties and dose-limiting central nervous system (CNS) toxicity. This report describes the physicochemical and pharmacological characterization of SDX-7320 (evexomostat), a polymer-drug conjugate of the novel METAP2 inhibitor (METAP2i) SDX-7539. In vitro binding, enzyme, and cell-based assays demonstrated that SDX-7539 is a potent and selective METAP2 inhibitor. In utilizing a high molecular weight, water-soluble polymer to conjugate the novel fumagillol-derived, cathepsin-released, METAP2i SDX-7539, limitations observed with prior generation, small molecule fumagillol derivatives were ameliorated including reduced CNS exposure of the METAP2i, and prolonged half-life enabling convenient administration. Multiple xenograft and syngeneic cancer models were utilized to demonstrate the anti-tumor and anti-metastatic profile of SDX-7320. Unlike polymer-drug conjugates in general, reductions in small molecule-equivalent efficacious doses following polymer conjugation were observed. SDX-7320 has completed a phase I clinical safety study in patients with late-stage cancer and is currently being evaluated in multiple phase Ib/II clinical studies in patients with advanced solid tumors.
The invention discloses a medicine for treating hyperlipemia. The medicine is a pharmaceutical composition which is prepared according to a certain process by taking pure natural plants and animals as raw materials. The medicine is convenient to carry, and can be taken anytime anywhere. The pharmaceutical composition comprises hawthorn, the root of red-rooted salvia, pseudo-ginseng, processed rheum officinale, Ligusticum wallichii, processed Polygonum multiflorum, flowers carthami, processed ginkgo leaves, processed glossy privet fruits, leeches, herba siegesbeckiae, rhizoma polygonati and rhizoma alismatis. Through massive clinical applications, the medicine is high in curative effect and free from toxic and side effects. The medicine disclosed by the invention is wide in source of raw materials, low in cost, simple in preparation method and free from three waste emission in production. The medicine disclosed by the invention matched with western medicines such as statins is better in curative effect.
The invention provides an antioxidant, a preparation method and application thereof, and belongs to the technical field of medical nano materials. The antioxidant is prepared by hydrophilic modification of nano antioxidant, and hydrodynamic diameter of the antioxidant is not more than 10 nm. The nanometer antioxidant has particle size of 1-2nm, has good antioxidant effect, and can effectively gather at kidney part to eliminate active oxygen in kidney part. The preparation method of the antioxidant comprises the following steps: hydrophilic modification is carried out on the nano antioxidant by adopting a hydrophilic material. The method is simple, easy to operate and suitable for industrial production. The antioxidant is used for eliminating active oxygen, has a good effect, has a long residence time in the kidney, can eliminate excessive active oxygen in the kidney, relieves the symptoms of acute kidney injury, and has important value and significance for treating medical acute kidney injury.
A composition for delivering an active agent to a patient. The composition includes a polymer core encapsulating the active agent and a mucoadhesive coating disposed about the core. The polymer may include covalently linked poly(ethylene glycol) chains, and the mucoadhesive coating may be selected to facilitate transfer of the particle through the intestinal mucosa. A molecular weight and cross-link density of the polymer may be selected such that the polymer core will decompose in a predetermined time interval. The fraction of the dose of the drug entering the system at circulation during the predetermined time interval may be between about 0.25% and about 25%. The composition may be formulated as a plurality of nanoparticles or microparticles that are combined with a pharmaceutically acceptable carrier to produce an edible or inhalable drug product.
Non-stunted group will be those with LAZ \>= 0.5 SD matching by age and sex with stunted group. Other criteria will be similar. No Intervention will be given to the groups in this proposed protocol.
Ischaemic stroke characterises impulsive cerebral-region hypoxia due to deep intracerebral arteriole blockage, often accompanied by permanent cerebral infarction and cognitive impairment. Thrombolysis with recombinant tissue plasminogen activator (rtPA) and thrombectomy remain the only guidance-approved therapies. However, emerging data draws clear links between such therapies and haemorrhage transformation, which occur when cerebral vasculature is damaged during ischaemia/reperfusion. Studies have shown that matrix metalloproteinases (MMPs) play a significant role in haemorrhage transformation, by depleting the extracellular matrix (ECM) and disrupting the blood brain barrier (BBB). Inhibitors of MMPs may be used to prevent ischaemic stroke patients from BBB disruption and haemorrhage transformation, particularly for those receiving rtPA treatment. Preclinical studies found that inhibition of MMPs with agents or in knock out mice, effectively reduced BBB disruption and infarct volume, leading to improved ischaemic stroke outcomes. At present, MMP inhibition is not an approved therapy for stroke patients. There remain concerns about timing, dosing, duration of MMP inhibition and selection of either broad spectrum or specific MMP inhibitors for stroke patients. This review aims to summarize current knowledge on MMP inhibition in ischaemic stroke and explore whether a broad spectrum or a specific MMP inhibitor should be used for ischaemic stroke patient treatment. It is crucial to inhibit MMP activities early and sufficiently to ensure BBB intact during ischaemia and reperfusion, but also to reduce side effects of MMP inhibitors to minimum. Recent advance in stroke therapy by thrombectomy could aid in such treatment with intra-arterially delivery of MMP inhibitors (and/or antioxidants).
AIMS: To perform dose-exposure-response analyses to determine the effects of finerenone doses.
MATERIALS AND METHODS: Two randomized, double-blind, placebo-controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m2 , a urine albumin-creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.8 mmol/L were included. Interventions were titrated doses of finerenone 10 or 20 mg versus placebo on top of standard of care. The outcomes were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR and kidney composite outcomes, assessed using nonlinear mixed-effects population pharmacokinetic (PK)/pharmacodynamic (PD) and parametric time-to-event models.
RESULTS: For potassium, lower serum levels and lower rates of hyperkalaemia were associated with higher doses of finerenone 20 mg compared to 10 mg (p < 0.001). The PK/PD model analysis linked this observed inverse association to potassium-guided dose titration. Simulations of a hypothetical trial with constant finerenone doses revealed a shallow but increasing exposure-potassium response relationship. Similarly, increasing finerenone exposures led to less than dose-proportional increasing reductions in modelled UACR. Modelled UACR explained 95% of finerenone's treatment effect in slowing chronic eGFR decline. No UACR-independent finerenone effects were identified. Neither sodium-glucose cotransporter-2 (SGLT2) inhibitor nor glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment significantly modified the effects of finerenone in reducing UACR and eGFR decline. Modelled eGFR explained 87% of finerenone's treatment effect on kidney outcomes. No eGFR-independent effects were identified.
CONCLUSIONS: The analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations. UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone's kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP-1RAs.
1387592 Interferon inducer KITASATO INSTITUTE 21 March 1972 [22 March 1971] 13036/72 Heading A5B Interferon inducers are isolated from Bordetella pertussis cultures. In one embodiment, B. pertussis is cultured in liquid medium and the medium separated from the cells and worked up to give the interferon inducer. The culture medium may be a modified Cohen- Wheeler medium and may be shaken. For separation, it may be subjected to ultrafiltration or chromatography. In another embodiment, the cultured cells are separated from the medium and disintegrated in an aqueous medium and the medium is separated from the insoluble cell debris and worked up to give the interferon inducer. The culture medium may be as above or it may be charcoal-agar. The cells may be disintegrated by sonic vibration in a sterile phosphate-buffer saline solution. The solution may be worked up by chromatography using as medium diethylaminoethyl cellulose, dextran or diethylaminoethyl dextran.
Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein-like 7 (OSBPL7) modulates the expression and function of ATP-binding cassette subfamily A member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Using mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. Although as expected, the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7 deficiency-related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7 deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study sheds new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthens the role of OSBPL7 as a novel therapeutic target.NEW & NOTEWORTHY OSBPL7 and ER stress comprise a central mechanism in glomerular injury. This study highlights a crucial link between OSBPL7 deficiency and ER stress in CKD. OSBPL7 deficiency causes ER stress, leading to podocyte apoptosis. There is a selective effect on lipid homeostasis in that OSBPL7 deficiency affects lipid homeostasis, altering cellular triglyceride but not cholesterol content. The interaction of ER stress and apoptosis supports that ER stress, not reduced autophagy, is the main driver of apoptosis in OSBPL7-deficient podocytes.
Patients in the standard fasting group were fasted for 24 hours after the first ESWL operation, and close observation during this fasting period. After 24 hours, according to the actual clinical needs, continue to fast until the next ESWL/ERCP operation, or change the diet to a general diet.
The present invention provides external application traditional Chinese medicine for treating hyperosteogeny diseases and a preparation method thereof, which relates to medical medicine. Aiming at the problem that hyperosteogeny diseases are still obstinate diseases at present, the present invention discloses a secret recipe handed down from generation and a preparation method thereof. The present invention has the purpose of providing special external application medicine which can effectively solve the defects and the shortages existing in the prior treatment at present so as to achieve satisfied treatment. The present invention not only can eliminate pain, but also can make degrading bones obtain the thorough nourishing and repair of essence and blood. Besides, the present invention has good favourable effect and high curative rate. The medicine prepared from Chinese herbal medicine as raw materials with a special method for preparation, and is an external application plaster. After the present invention is applied to affected parts, the present invention can make transdermal absorption directly reach the vascular plexus of a synovial membrane. The present invention has medicine force concentration and obvious efficiency. The present invention has the advantages of convenient and safe medicine taking, no toxic and side effect, conspicuous curative effect, short treatment course, obvious effect and low cost. The present invention can be externally applied for treatment, can be absorbed by a body surface, directly reaches lesions, and has no stimulation to the mucous membrane of a stomach intestine and functional damage for the liver and kidney because of oral administration. Therefore, the present invention is optimized as a preparation for social charities and disease treatment.
The present invention discloses a traditional Chinese medicine compound preparation for treating cardiovascular and cerebrovascular diseases and a preparation method thereof. The present invention is formed by using the raw materials or alcohol of the raw materials and water or extract of water as active components: 500 to 1125g of hemlock parsley, 750 to 1688g of kudzu roots and 750 to 1688g of tribulus fruits. Alcohol of the three raw materials and water or extract of water are mixed evenly and are prepared into a required dosage form. The medicine has the functions of blood activation, channel invigoration, clot absorption and pain alleviation. The present invention is used for treating diseases, such as headache, cephalagra, or rigidity of nape and headache, or sequela of apoplexy accompanied with hemianesthesia and hemiplegia, or cerebral thrombosis, cerebral infarction sequelae, etc. caused by channel blocking. The Chinese materia medica preparation has the advantages of exact curative effect, safe use and stable quality, and the effective rate can reach 92% by clinical tests.
Usual care as provided by each of our 4 community-based organization partners. Usual care can include but is not limited to support groups, patient navigation, individual, couple or family therapy.
General Drowsiness: Since drowsiness may occur with the use of PRUDOXIN® Cream, patients should be warned of the possibility and cautioned against driving a car or operating dangerous machinery while using this drug. Patients should also be cautioned that their response to alcohol may be potentiated.

Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be observed closely for confusion and oversedation when started on PRUDOXIN® Cream. (See PRECAUTIONS - Geriatric Use.)

Use under occlusion: Occlusive dressings may increase the absorption of most topical drugs; therefore, occlusive dressings should not be utilized with PRUDOXIN® Cream.

Contact sensitization: Use of PRUDOXIN® Cream can cause Type IV hypersensitivity reactions (contact sensitization) to doxepin.
LoFric, hydrophilic urinary catheter for single use. The study device is based on commercially available hydrophilic urinary catheters for intermittent catheterization, but with a different coating process than the comparator. Treatment Period One will last 1 week.
Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of PD1-CD19-CART will be infused on day 0.
The invention provides a nucleic acid aptamer and application thereof in detecting M protein, so as to prepare a product for detecting IBV virus or preventing and treating IBV virus. The nucleotide sequence of the nucleic acid aptamer provided by the invention is SEQ ID NO. 1 or SEQ ID NO. 2. The 5 'end or the 3' end of the nucleic acid aptamer is combined or modified with biotin, digoxin, fluorescent substances, amino groups, amino acids and derivatives thereof, vitamins, nano luminescent materials, enzymes or colloidal gold and other molecules capable of improving the functions of the nucleic acid aptamer. The invention also aims to provide application of the nucleic acid aptamer in preparation of a reagent or a kit for detecting IBV. The invention also aims to provide application of the nucleic acid aptamer in preparing a medicament for treating IBV. The aptamer capable of specifically binding IBV M protein provided by the invention can be applied to medicines, reagents and molecular probes, so that IBV viruses can be effectively detected or prevented and treated.
BACKGROUND: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular diseases. It was investigated whether ultrasound provides a better prediction of cardiovascular events compared to the prospective cardiovascular Münster study (PROCAM) score and whether treatment of subjects with advanced atherosclerosis with statins improves the prognosis.
METHOD: Between 2009 and 2016 a total of 4482 subjects (41% women) aged 35-65 years with no signs of cardiovascular disease underwent carotid artery ultrasound examination. Total plaque area (TPA) and maximum plaque thickness were measured. The PROCAM score was used to determine the cardiovascular risk.
RESULTS: The median follow-up time was 77 months (6.4 years) for the men and 74 months (6.2 years) for the women. Events, such as myocardial infarction, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA), occurred in 131 (3.4%) of the 3833 subjects with complete follow-up data. The prediction of cardiovascular events was better with ultrasound than with the PROCAM score. Ultrasound predicted 79.4% of 131 events and the PROCAM score predicted 22.9%. Treatment of subjects with advanced atherosclerosis (types III, IV b) with a statin significantly improved the prognosis. The event rate was 12.6% in men and women in the treated group vs. 31.5% (p < 0.0001) in the untreated group. Mortality (from any cause) was significantly lower in men treated with statins (p = 0.0148).
CONCLUSION: The prediction of cardiovascular events was better with plaque burden measurements than with the PROCAM score. Treatment with statins in subjects with advanced carotid atherosclerosis (types III-IV b findings on ultrasound) significantly improved the prognosis in a nonrandomized observational study.
Patients who randomize to the hypertonic saline arm will be prescribed a nebulizer device to nebulize hypertonic saline (7%) twice daily for 12 weeks. Hypertonic saline (3%) can be prescribed in the case of poor tolerability of the 7% solution.
Patients will not receive the sound S1 and sound S2 while they generate a correct outcome of Emotional Attention Bias Modification(EABM). During REM sleep, they will receive the same sound as the experimental group (S1 and S2) under the same conditions.
Treatment with latanoprost/timolol fixed combination for 3 months. 24-hour pressure monitoring.
Oral atypical antipsychotic will be administered as per local label practice for 24 months. Participants will be switched to another atypical oral therapy as per Investigator's discretion.
Control group: Mallinckrodt HiLo(TM) endotracheal tube. Intracuff pressures of the tubes every 10 minutes, Adult patients under general anesthesia with Mallinckrodt Hi-Lo(TM) tube.
According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.