anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND AND PURPOSE: The discovery of new bromo- and extra-terminal inhibitors presents new drugs to treat osteoarthritis (OA).
EXPERIMENTAL APPROACH: The new drug, BBC0403, was identified in the DNA-encoded library screening system by searching for compounds that target BRD (bromodomain-containing) proteins. The binding force with BRD proteins was evaluated using time-resolved fluorescence energy transfer (TR-FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12-week-old male C57BL/6 mouse model, and intra-articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA-seq.
KEY RESULTS: TR-FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti-OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 μM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF-κB and MAPK signalling pathways.
CONCLUSION AND IMPLICATIONS: This study demonstrated that BBC0403 is a novel BRD2-specific inhibitor and a potential i.a.-injectable therapeutic agent to treat OA.
Preeclampsia (PE) is characterized by de novo hypertension (HTN) and is often associated with intrauterine growth restriction (IUGR). Hallmarks of PE are placental ischemia, decreased nitric oxide (NO) bioavailability, oxidative stress (OS), and organ damage in the kidneys and brain. This study aims to characterize a new model of PE using pregnant IUGR rats from hypertensive placental ischemic dams. It is hypothesized that pregnant IUGR rats from hypertensive placental ischemic dams will have elevated blood pressure (BP), OS, and organ damage. In this study, pregnant rats are divided into two groups: normal pregnant (NP) and hypertensive placental ischemic dams (RUPP). Offspring from NP and RUPP dams were mated at 10 weeks of age to generate pregnant IUGR (IUGR Preg) and pregnant control (CON Preg) rats. BP and other markers of PE were evaluated during late gestation. Pregnant IUGR rats had elevated BP and systemic OS. The maternal body weight of pregnant IUGR rats and their pups' weights were decreased, while the brains were enlarged with elevated OS. In summary, pregnant IUGR rats, born from hypertensive placental ischemic dams, have HTN and increased systemic and brain OS, with larger brain sizes and smaller pups. Furthermore, this study shows that pregnant IUGR rats exhibit a preeclamptic-like phenotype, suggesting a new epigenetic model of PE.
A method for oral administration of an active ingredient to a subject is provided whereby a plurality of bubbles containing the active ingredient t are formed in a small intestinal of the subject. The method includes administering orally to the subject an effective amount of the above-mentioned pharmaceutical composition. The pharmaceutical composition includes a drug layer and an enteric coating layer. The drug layer comprises an active ingredient, a surfactant, an acidic component and an effervescent ingredient. The active ingredient comprises a nucleic acid, a peptide or a protein. When the acidic component of the drug layer is dissolved in the small intestinal to react with the effervescent ingredient for generating carbon dioxide and the plurality of bubbles containing the active ingredient, and the active ingredient is embedded in a gap formed between an inner layer and an outer layer of an double-layer structure formed by the surfactant.
Disclosed are dosage forms and related methods, that include a first population of synthetic nanocarriers that have one or more first antigens coupled to them, one or more second antigens that are not coupled to the synthetic nanocarriers, and a pharmaceutically acceptable excipient. See Fig. 1. WO 2011/150264 PCT/US2011/038218 10000000 [ M2e u Fig. 1 10000000 E] M2e 100000 K , Fig. 2
This is a randomized, open-label, parallel-group, single-dose study. Patients will undergo screening evaluations to determine eligibility within 28 days prior to study drug administration. About 36 patients will be randomized in a 1:1:1 ratio to 1 of 3 treatment groups. Patients will be admitted to the clinical facility the day before dosing (Day 0) and will be receiving an IM injection of study drug and completing the assigned study activity including PK sample collection on Day 1. Patients will be discharged on Day 2 after PK collection. All patients will return to the clinical site at designated study days for PK sample collections and assigned clinical procedures. End of study evaluation will be completed on Day 120.

Pharmacokinetics of the study medication will be assessed as primary outcome. Participants' safety will be monitored throughout the study.
The mechanism of action of captopril has not yet been fully elucidated. Its beneficial effects in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. However, there is no consistent correlation between renin levels and response to the drug. Renin, an enzyme synthesized by the kidneys, is released into the circulation where it acts on a plasma globulin substrate to produce angiotensin I, a relatively inactive decapeptide. Angiotensin I is then converted by angiotensin converting enzyme (ACE) to angiotensin II, a potent endogenous vasoconstrictor substance. Angiotensin II also stimulates aldosterone secretion from the adrenal cortex, thereby contributing to sodium and fluid retention.

Captopril prevents the conversion of angiotensin I to angiotensin II by inhibition of ACE, a peptidyldipeptide carboxy hydrolase. This inhibition has been demonstrated in both healthy human subjects and in animals by showing that the elevation of blood pressure caused by exogenously administered angiotensin I was attenuated or abolished by captopril. In animal studies, captopril did not alter the pressor responses to a number of other agents, including angiotensin II and norepinephrine, indicating specificity of action.

ACE is identical to “bradykininase,” and captopril may also interfere with the degradation of the vasodepressor peptide, bradykinin. Increased concentrations of bradykinin or prostaglandin E2 may also have a role in the therapeutic effect of captopril.

Inhibition of ACE results in decreased plasma angiotensin II and increased plasma renin activity (PRA), the latter resulting from loss of negative feedback on renin release caused by reduction in angiotensin II. The reduction of angiotensin II leads to decreased aldosterone secretion, and, as a result, small increases in serum potassium may occur along with sodium and fluid loss.The antihypertensive effects persist for a longer period of time than does demonstrable inhibition of circulating ACE. It is not known whether the ACE present in vascular endothelium is inhibited longer than the ACE in circulating blood.
This study will use non-invasive approaches (surface electrodes, encoders, torque meters, motors) to study muscle delay and how muscle fatigues for both individuals possessing movement disorders and healthy individuals. Individuals with movement disorders are often susceptible to partial or total paralysis. This paralysis often leads to an increasingly sedentary lifestyle. By implementing the intelligent closed-loop control of FES-cycling, FES-therapy can be made more effective, combating the effects of sedentary lifestyles. Using data obtained from non-invasive sensors, the study team will apply analytical techniques to quantify FES muscle delay and how well individuals can track a desired cadence as the muscle fatigues. A challenge associated with FES-induced cycling is that there exists a delay between the time when FES is applied and the time when the muscle contracts. There is likewise a delay between the time FES is removed and the time the muscle ceases to contract. Previous studies have measured this delay and determined that it varies with fatigue. A goal of this project is to measure this delay on an FES-cycle and to determine how this delay varies as a result of FES-induced cycling. Another goal is to determine what effect the crank angle has on the delay as well as on the muscle control effectiveness. This study will provide insight into how engineering can be combined with healthcare and therapy to better both fields and bridge the gap between engineering and medicine.
Patients followed during 2 years after an initiation of ziconotide. These patients will be recruited retrospectively or prospectively.
A process is provided for growing microflora of the order Thraustochytriales such as Thraustochytrium, Schizochytrium, and mixtures thereof, in fermentation medium containing non-chloride containing sodium salts, in particular sodium sulfate. In a preferred embodiment, the process produce, microflora having a cell aggregate size useful for the production of food products for use in aquaculture. Further provided is a food product which includes Thraustochytrium, Schizochytrium, and mixture thereof, and a component selected from flaxseed, reapedeed, soybean and avocado meal. Such a food product includes a balance of long chain and short chain omega-3 highly unsaturated fatty acids. A method for increasing omega-3 highly unsaturated fatty acid content of eggs by feeding a feed to poultry. The feed contains the microorganisms of the order Thraustochytriales having a omega-3 highly unsaturated fatty acid content of more than 6.7 percent of total cell dry weight. The microorganisms include strains of Schizochytrium and Thraustochytrium such as ATCC No.(s) 20888 and 20889, and ATCC No.(s) 20890, 20891 and 20892, respectively. Also provided are eggs containing an increased amount of these fatty acids.
The aim of the current trial is to compare the standard 3-day regimen of artemether-lumefantrine to a 5-day regimen of artemether-lumefantrine in a group of pregnant women and a control of non-pregnant women with uncomplicated P. falciparum malaria. The pharmacokinetics of lumefantrine is modified in pregnancy and the standard regimen used for treatment of adults might not be sufficient to cure malaria, therefore exposing pregnant women to sub-therapeutic drug levels and increased risk of clinical failure. Previous pharmacokinetic studies have shown that the standard 3-day treatment during pregnancy results in reduced plasma concentrations of artemether, dihydroartemisinin and lumefantrine and a faster elimination of lumefantrine. Low lumefantrine plasma concentrations at day 7 are associated with therapeutic failure. Population-based simulations suggest that increased dose and treatment duration are needed for adequate drug exposure in these patients. We propose to assess the pharmacokinetics of a longer regimen of artemether-lumefantrine, (10 doses of artemether-lumefantrine over five days) compared to the standard regimen, (6 doses of artemether-lumefantrine over three days) in a small group of pregnant African women with uncomplicated P. falciparum malaria. The longer regimen should ensure that curative plasma concentration of lumefantrine is reached, and is unlikely to result in any increased frequency of adverse events.
Intradermal injection (ID) of AlloStim(TM) (1ml) on day 4 and 7. AlloVax Treatment: ID injection of AlloSim(TM) (1 ml) followed immediately by the ID injection of CRCL (1ml) on day 11 and 14 in same location on the left arm and on day 18 and 21 in the same location on the right arm. Intravenous infusion of AlloStim(TM)(5ml) and a CRCL alone Intradermal injection on Day 27.
Clinical decision-support systems (CDSS) are designed to solve knowledge-intensive tasks for supporting decision-making processes. Although many approaches for designing CDSS have been proposed, due to high implementation costs, as well as the lack of interoperability features, current solutions are not wellestablished across different institutions. Recently, the use of standardized formalisms for knowledge representation as terminologies as well as the integration of semantically enriched clinical information models, as openEHR Archetypes, and their reuse within CDSS are theoretically considered as key factors for reusable CDSS. The investigators already successfully transferred their concept into a prototype and evaluated the practicability on clinical data sets and in close cooperation between the clinicians and the technical experts. To the author's knowledge, currently, there are no openEHR based CDSS approaches which have been implemented and evaluated with such complex and important clinical contexts. Hence, the first clinically evaluated CDSS based on openEHR was successfully designed. When enhancing the described approach and implementing a live system, it might support clinicians to identify the patient's course of disease at an early stage, which can lead to better outcome for the patient. Furthermore, the system can serve as a basis for integrating (cross-institutional) machine learning components that could facilitate dealing with other high-complex decision problems or revealing yet unknown disease patterns.
The patients' lungs ventilation will be initiated with a peak airway pressure that provided a tidal volume of 8 ml.kg-1. R.R will be adjusted to achieve an arterial PaCO2 4.5-6 kPa and FiO2 will be increased to 1.0 during OLV.
The aim of this study is to investigate the potential of TEA to treat abdominal pain in participants with IBS with constipation (IBS-C). The study also aims to compare the electrical neuromodulation therapy (TEA) with medical neuromodulation therapy (escitalopram) in their ability to treat abdominal pain and improve the autonomic dysfunction in participants with IBS-C. This project will investigate the impact of 3 active treatment interventions vs. a sham control intervention on abdominal pain and other IBS symptoms in participants with IBS-C. This is a parallel-group study in which the participants will be divided into 4 treatment groups designed to investigate the feasibility of TEA using optimized parameters in comparison with medical neuromodulation therapy (escitalopram) and sham-TEA. The treatment will be home-based and last for a period of 8 weeks. To preserve scientific integrity and effective masking, certain details of arms and interventions will be made more precise upon or prior to reporting results
Objective : This study aimed to investigate whether changes in carotid artery corrected flow time (ΔFTc bolus ) and carotid artery peak flow velocity respiratory variation (Δ V peak bolus ) induced by the fluid challenge could reliably predict fluid responsiveness in mechanically ventilated patients with a tidal volume < 8 mL/kg Predicted Body Weight while preserving spontaneous breathing. Methods : Carotid artery corrected flow time, Δ V peak, and hemodynamic data were measured before and after administration of 250 mL crystalloids. Fluid responsiveness was defined as a 10% or more increase in stroke volume index as assessed by noninvasive cardiac output monitoring after the fluid challenge. Results : A total of 43 patients with acute circulatory failure were enrolled in this study. Forty-three patients underwent a total of 60 fluid challenges. The ΔFTc bolus and Δ V peak bolus showed a significant difference between the fluid responsiveness positive group (n = 35) and the fluid responsiveness negative group (n = 25). Spearman correlation test showed that ΔFTc bolus and Δ V peak bolus with the relative increase in stroke volume index after fluid expansion ( r = 0.5296, P < 0.0001; r = 0.3175, P = 0.0135). Multiple logistic regression analysis demonstrated that ΔFTc bolus and Δ V peak bolus were significantly correlated with fluid responsiveness in patients with acute circulatory failure. The areas under the receiver operating characteristic curves of ΔFTc bolus and Δ V peak bolus for predicting fluid responsiveness were 0.935 and 0.750, respectively. The optimal cutoff values of ΔFTc bolus and Δ V peak bolus were 0.725 (sensitivity = 97.1%, specificity = 84%) and 4.21% (sensitivity = 65.7%, specificity = 80%), respectively. Conclusion : In mechanically ventilated patients with a tidal volume < 8 mL/kg while preserving spontaneous breathing, ΔFTc bolus and Δ V peak bolus could predict fluid responsiveness. The predictive performance of ΔFTc bolus was superior to Δ V peak bolus .
The invention provides a pharmaceutical composition for treating liver diseases. The pharmaceutical composition comprises buttercups products and external creams, and is used for treating hepatic ascites, cirrhosis, fast repairing wound surfaces, treating skin ulcer, scars and burns, and relieving pain and itching. The preparation method of the pharmaceutical composition is simple, the cost is low, and the side effects caused by oral administration of patients and injections can be avoided. The external cream is prepared from the following traditional Chinese medicines by weight: 500-10000g of edible vegetable oil, 5-500g of polygonaceae plants, 10-500g of beewax, 10-500g of borneolum syntheticum and 10-500g of propolis. When the external cream is used for treating wound surfaces, the effects of relieving pain and itching and diminishing inflammation are strong. The wound surfaces are easily banded up after being applied with the cream, and no scars are left after recovery.
Due to the rarity of radiation-induced (RIS) or previously irradiated recurrent (PIRS) sarcomas, no guidelines nor randomized prospective clinical trials on this topic exist. Thus the management of RIS and PIR is challenging. The only curable modality in non-metastatic RIS/PIRS is radical resection with wide negative margins. The role of secondary radiotherapy in locally advanced RIS/PIRS is unclear, mostly due to the concerns about possible severe side effects after re-irradiation.

The addition of deep hyperthermia to irradiation and in the prolonged gap between the end of moderately hypofractionated radiotherapy (with or without integrated boost) and surgery may allow obtaining the long-term local control with the maintenance of a good treatment tolerance Hyperthermia is a method of increasing the temperature in the tumor to damage cancer cells with minimum injury to the normal cells. It should be combined with another treatment modality (radio- or chemotherapy) rather than used alone. Its efficacy was proven in clinical trials. Treatment tolerance is usually very good.
PURPOSE: To obtain the subject formulation comprising a protein, a buffer and alanine and mannitol at a specific ratio, excellent in stability of formulation and reconstitution, etc., to liquid form and useful for reconstitution, etc., of solution for subcutaneous, intravenous or intramuscular injection to human and animals. CONSTITUTION: This formulation comprises (A) a protein such as a hormone (e.g. human growth hormone), an enzyme (e.g. urate oxidase) or cytokine (e.g. interleukin-13), (B) a buffer such as phosphate buffer, (C) an alanine such as crystalline alanine and (D) a mannitol such as amorphous-shaped mannitol and contains the components C and D in 0.1-1 weight ratio of components C/D. Furthermore, in the formulation, the freeze-dried product comprises an amorphous phase and a crystalline phase and the amorphous phase consists mainly of the components A and D and the crystal phase consists mainly of the component C.
Recognition of obesity as a treatable trait of asthma, impacting its development, clinical presentation and management, is gaining widespread acceptance. Obesity is a significant risk factor and disease modifier for asthma, complicating treatment. Epidemiological evidence highlights that obese asthma correlates with poorer disease control, increased severity and persistence, compromised lung function and reduced quality of life. Various mechanisms contribute to the physiological and clinical complexities observed in individuals with obesity and asthma. These encompass different immune responses, including Type IVb, where T helper 2 cells are pivotal and driven by cytokines like interleukins 4, 5, 9 and 13, and Type IVc, characterised by T helper 17 cells and Type 3 innate lymphoid cells producing interleukin 17, which recruits neutrophils. Additionally, Type V involves immune response dysregulation with significant activation of T helper 1, 2 and 17 responses. Finally, Type VI is recognised as metabolic-induced immune dysregulation associated with obesity. Body mass index (BMI) stands out as a biomarker of a treatable trait in asthma, readily identifiable and targetable, with significant implications for disease management. There exists a notable gap in treatment options for individuals with obese asthma, where asthma management guidelines lack specificity. For example, there is currently no evidence supporting the use of incretin mimetics to improve asthma outcomes in asthmatic individuals without Type 2 diabetes mellitus (T2DM). In this review, we advocate for integrating BMI into asthma care models by establishing clear target BMI goals, promoting sustainable weight loss via healthy dietary choices and physical activity and implementing regular reassessment and referral as necessary.
Patients take a single dose of KC1036 for the pharmacokinetic study, then off for 5 days before the first cycle begins. In the subsequent treatment cycles, KC1036 are given orally once daily, 21 days as a cycle.
High Intensity endurance physical exercise, intensity measured on Borg Scale with progression from Borg 10-13 (50% of maximum) to 17-18 (80 % of maximum). One hour of exercise twice weekly for 12 weeks supervised by physiotherapists.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
PURPOSE:To prepare the titled preparation having improved heat stability and light stability, preventing the discoloration, degradation and nonhomogeneous distribution of the active component, by compounding sodium azulenesulfonate with sodium laurylsulfate at a specific ratio. CONSTITUTION:100pts.wt. of sodium azulenesulfonate (AzSNa) is compounded with >=0.01pts.wt. of sodium laurylsulfate (LaSNa) to obtain an AzSNa-containing solid preparation. The content of AzSNa in the whole preparation is 0.01- 5wt%, and the preparation is administered in the form of granule, powder, fine powder, tablet, pill, capsule, etc. A granule stable against heat and light can be produced by granulating, drying and further refining the shape of the granule. A tablet having high stability and resistant to the degradation with time can be produced by adding magnesium stearate and perfumery to the composition, and tableting the mixture. The amount of the binder is 0.5-15wt% of the whole preparation.