anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Sepsis is a severe systemic inflammatory disorder manifested by a dysregulated immune response to infection and multi-organ failure. Numerous studies have shown that elevated ferritin levels exist as an essential feature during sepsis and are able to suggest patients' prognoses. At the same time, the specific mechanism of ferritin-induced inflammatory injury remains unclear.
METHODS: Hyper-ferritin state during inflammation was performed by injecting ferritin into a mouse model and demonstrated that injection of ferritin could induce a systemic inflammatory response and increase neutrophil extracellular trap (NET) formation.Padi4-/-, Elane-/- and Cybb-/- mice were used for the NETs formation experiment. Western blot, immunofluorescence, ELISA, and flow cytometry examined the changes in NETs, inflammation, and related signaling pathways.
RESULTS: Ferritin induces NET formation in a peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), and reactive oxygen species (ROS)-dependent manner, thereby exacerbating the inflammatory response. Mechanistically, ferritin induces the expression of neutrophil macrophage scavenger receptor (MSR), which promotes the formation of NETs. Clinically, high levels of ferritin in patients with severe sepsis correlate with NETs-mediated cytokines storm and are proportional to the severity of sepsis-induced lung injury.
CONCLUSIONS: In conclusion, we demonstrated that hyper-ferritin can induce systemic inflammation and increase NET formation in an MSR-dependent manner. This process relies on PAD4, NE, and ROS, further aggravating acute lung injury. In the clinic, high serum ferritin levels are associated with elevated NETs and worse lung injury, which suggests a poor prognosis for patients with sepsis. Our study indicated that targeting NETs or MSR could be a potential treatment to alleviate lung damage and systemic inflammation during sepsis. Video Abstract.
To explore whether SGLT2-Inhibition has a beneficial effect on Sleep Disordered Breathing (SDB) in advanced heart failure patients. This project proposes to carry out research that addresses the established, but in clinical practice under-recognized association between Sleep Disordered Breathing (SDB) and a worse prognosis in patients with heart failure (HF). SDB is highly prevalent in the HF population. Multiple studies have shown that HF accompanied by SDB is associated with an increased mortality compared to the absence of SDB. Two major types of SDB are prevalent in HF: Obstructive Sleep Apnea (OSA) and Central Sleep Apnea (CSA). Mechanistically, it has been proposed that SDB impacts the neurohumoral axis and systemic metabolism and therefore has particularly detrimental effects on the HF patient population. Therapeutic options for the treatment of SDB are limited. Heart Failure is a multisystemic disease leading to maladaptive cardiac and systemic metabolic changes. Recently, with SGLT2-Inhibitors a new drug class has been approved for the treatment of advanced heart failure. This is the first drug class in the HF drug armamentarium targeting cardiometabolic mechanisms. This study seeks to improve the health of individuals with heart failure by exploring whether SGLT2-Inhibition has a beneficial effect on SDB (OSA and CSA) in advanced heart failure patients and therefore may be a novel therapeutic option for the treatment of SDB in advanced HF. The specific aim of this project is to assess the effect of therapy with a SGLT2-I on SDB in ambulatory advanced HF patients by using the WatchPAT-derived apnea-hypopnea index as well as subjective measures of sleep quality using the Berlin Questionnaire and Epworth Sleepiness Scale.
The invention relates to an externally applied medicinal solution for treating hyperosteogeny, cervical spondylosis and lumbar disc herniation. The externally applied medicinal solution comprises the following medicinal materials: 10-20g of angelica sinensis, 10-20g of peach seeds, 10-20g of safflower, 10-20g of frankincense, 10-20g of myrrh, 10-20g of suberect spatholobus stem, 10-20g of clematis root, 10-20g of dragon's blood and 500g of vegetable oil. A preparation method comprises the following steps: adding 500g of vegetable oil into a stainless steel pan, boiling the oil to 150 degrees, firstly adding angelica sinensis, peach seeds, safflower, clematis root and suberect spatholobus stem into the pan, boiling with slow fire for 30min, then adding crushed frankincense and myrrh, frying for 10min, cooling until the temperature of the oil is 60 degrees, then adding ground dragon's blood into the medicinal oil, uniformly stirring, removing residues and bottling. The crushed and ground medicines in the formula do not need to be screened. A medium of the externally applied medicinal solution provided by the invention has good soaking property, the medicines can directly achieve an affected part to play the roles to a greatest extent, and the purpose of 'relieving pain by dredging' is achieved. The externally applied medicinal solution provided by the method disclosed by the invention has no pain, no side effects, short single treatment time, sufficient medicinal source, no need of oral administration of the medicines and reliable curative effect, is easy to be accepted by a patient, is environment-friendly and is suitable for popularization and application.
The invention relates to a preparation technology of an integrated ephedra, aconite and asarum decoction novel dosage form. The novel dosage form comprises the following active ingredients in parts by weight: 6 parts of ephedra, 9 parts of aconite and 6 parts of asarum. The production process comprises the following steps: extraction in aqueous alcohol, ultrasonic grinding and extraction, microwave extraction, decoction in water and concentration, spray drying, high-pressure homogenizing, nanoscale grinding, nanoparticle preparation and the like. In the method, the stress is laid on the advantages of multi-synergy and multi-target effects of nano traditional Chinese medicines. After scale industrial production, the production cost can be substantially lowered, the product quality can be improved and the targeting and slow/controlled release properties of the medicines are stronger. After the novel dosage form is prepared into films, the films can be stuck to the skins of the human bodies and are used for treating the diseases through percutaneous absorption.
The present invention provides a synergistic topically applied personal hygiene product comprising 8 to 12% by wt. of Povidone-Iodine complex, 0.5 to 1.0% by wt. of potassium iodide, 1 to 10% by wt. of phosphate, 5 to 15% by wt. chlorhexidine acetate, 5 to 20% by wt. of alcohol, 1 to 5% by wt. of citric acid and the remaining being pharmaceutically acceptable excipients which provides disinfection against commonly known pathogens and prevents transmission of most of the sexually transmitted diseases and a process for preparing the same.
PURPOSE: To obtain an aseptic infusible powder without deteriorating the stability and quality of an antibiotic substance by spray-drying a solution of an antibiotic substance in a circulating inert gas atmosphere in the presence of a salt-forming agent. CONSTITUTION: An antibiotic substance, preferably a β-lactam antibiotic substance (e.g. ampicillin or piperacillin) is dissolved at a concentration of 1-50wt.%, preferably 8-25wt.% in an aqueous mixture consisting of <=80vol.% of water, methanol or ethanol, 70vol.% of acetone and 50vol.% of isopropyl alcohol in the presence of a salt-forming agent (e.g. sodium hydroxide or sodium salt of the alcohol used in the composition). The solution is subjected to ultrasonic treatment and degassing treatment and spray-dried in a circulating inert gas atmosphere to obtain the objective powder. The spray-drying is carried out at a solution temperature of 50-550 deg.C, preferably 150-240 deg.C and an extracted powder temperature of 90-200 deg.C, preferably 95-130 deg.C.
Nuclear factor κB (NF-κB) plays roles in various diseases. Many inflammatory signals, such as circulating lipopolysaccharides (LPSs), activate NF-κB via specific receptors. Using whole-genome CRISPR-Cas9 screens of LPS-treated cells that express an NF-κB-driven suicide gene, we discovered that the LPS receptor Toll-like receptor 4 (TLR4) is specifically dependent on the oligosaccharyltransferase complex OST-A for N-glycosylation and cell-surface localization. The tool compound NGI-1 inhibits OST complexes in vivo, but the underlying molecular mechanism remained unknown. We did a CRISPR base-editor screen for NGI-1-resistant variants of STT3A, the catalytic subunit of OST-A. These variants, in conjunction with cryoelectron microscopy studies, revealed that NGI-1 binds the catalytic site of STT3A, where it traps a molecule of the donor substrate dolichyl-PP-GlcNAc2-Man9-Glc3, suggesting an uncompetitive inhibition mechanism. Our results provide a rationale for and an initial step toward the development of STT3A-specific inhibitors and illustrate the power of contemporaneous base-editor and structural studies to define drug mechanism of action.
Formoterol Fumarate Inhalation Solution was evaluated in a 12-week, double-blind, placebo- and active-controlled, randomized, parallel-group, multicenter trial conducted in the United States. Of a total enrollment of 351 adults (age range: 40 to 86 years; mean age: 63 years) with COPD who had a mean pre-bronchodilator FEV1 of 1.34 liters (44% of predicted), 237 patients were randomized to Formoterol Fumarate Inhalation Solution 20 mcg or placebo, administered twice daily via a PARI-LC Plus® nebulizer with a PRONEB® Ultra compressor. The diagnosis of COPD was based upon a prior clinical diagnosis of COPD, a smoking history (at least 10 pack-years), age (at least 40 years), and spirometry results (pre-bronchodilator baseline FEV1 at least 30% and less than 70% of the predicted value, and the FEV1/FVC less than 70%). About 58% of patients had bronchodilator reversibility, defined as a 10% or greater increase in FEV1 after inhalation of 2 actuations (180 mcg) of albuterol from a metered dose inhaler. About 86% (106) of patients treated with Formoterol Fumarate Inhalation Solution and 74% (84) of placebo patients completed the trial.

Formoterol Fumarate Inhalation Solution 20 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by serial FEV1 for 12 hours post-dose; the primary efficacy analysis) compared to placebo when evaluated at endpoint (week 12 for completers and last observation for dropouts). Similar results were seen on Day 1 and at subsequent timepoints during the trial.

Mean FEV1 measurements at Day 1 (Figure 1) and at endpoint (Figure 2) are shown below.

* Figures show least-squares means adjusted for baseline FEV1   
Patients treated with Formoterol Fumarate Inhalation Solution used less rescue albuterol during the trial compared to patients treated with placebo. 

Examination of age (≥ 65 or younger) and gender subgroups did not identify differences in response to Formoterol Fumarate Inhalation Solution. There were too few non-Caucasian subjects to assess differences in populations defined by race adequately.

In the 12-week study, 78% of subjects achieved a 15% increase from baseline FEV1 following the first dose of Formoterol Fumarate Inhalation Solution 20 mcg. In these subjects, the median time to onset of bronchodilation, defined as 15% increase in FEV1, was 11.7 minutes. When defined as an increase in FEV1 of 12% and 200 mL, the time to onset of bronchodilation was 13.1 minutes after dosing. The median time to peak bronchodilator effect was 2 hours after dosing.
The present invention relates to a ceramide stabilizing cosmetic composition comprising multi-layer nanogel emulsion and a method for manufacturing multi-layer nanogel emulsion. The ceramide stabilizing cosmetic composition of the present invention is formed by mixing and agitating a water phase portion and a poorly water soluble lipid portion and then inserting an oil phase portion. Various kinds of ceramide and depravities thereof which are poorly water soluble skin lipid elements are enhanced. Crystallizability of ceramide is reduced. At the same time, ceramide is oriented with an element having excellent mixing properties with respect to ceramide. Afterwards, an emulsifier, having powerful self-assembly properties, and an element of the water phase portion comprising a polymer capable of hydration membrane coating on an interface are optimized with sol-gel properties depending on a temperature. Accordingly, multi-layer nanogel is emulsified by stabilizing content of ceramide which is up to 20 wt%. Therefore, ceramide can be mixed into a cosmetic in an easy manner without a secession phenomenon. In addition, the ceramide stabilizing cosmetic composition has an excellent effect of moisturizing skin and preventing skin troubles such as atopic dermatitis by recovering a damaged skin barrier by enabling ceramide to effectively penetrate a skin intercellular substance.
The study intervention will be saline irrigation (240 mL) followed by azelastine spray (137 mcg/spray) and mometasone spray (50 mcg/spray). Participants will have to dissolve the salt packet in a 240 mL sinus rinse bottle to create the saline solution. All participants will be instructed to perform the following twice a day: irrigation of right and left nasal cavity with half of the saline solution for each side followed by 2 sprays per nostril of both of the nasal sprays.
Study J:Insulin Degludec Administered at the Same Time Each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes in Pediatric Patients 1 Year of Age and Older

The efficacy of Insulin Degludec was evaluated in a 26-week, randomized, open label, multicenter trial in 350 patients with type 1 diabetes mellitus (Study J). Patients were randomized to Insulin Degludec once-daily or insulin detemir once or twice-daily. Subjects on a twice-daily insulin detemir regimen were dosed at breakfast and in the evening either with the main evening meal or at bedtime. Insulin aspart was administered before each main meal in both treatment arms. At end of trial, 36% used insulin detemir once daily and 64% used insulin detemir twice daily. 

The mean age of the trial population was 10 years; 24% were ages 1-5 years; 39% were ages 6-11 years and 36% were ages 12-17 years. The mean duration of diabetes was 4 years. 55% were male. 75% were White, 3% Black or African American. 3% were Hispanic. The mean z-score for body weight was 0.31.

At week 26, the difference in HbA1c reduction from baseline between Insulin Degludec and insulin detemir was 0.15% with a 95% confidence interval of [-0.03%; 0.33%] and met the pre-specified non-inferiority margin (0.4%). See Table 8.

Table 8: Results at Week 26 in a Trial Comparing Insulin Degludec to Insulin Detemir in Pediatric Patients 1 Year of Age and Older with Type 1 Diabetes Mellitus Receiving Insulin Aspart at Mealtimes

     ±The change from baseline to end of treatment visit in HbA1c was analyzed using ANOVA with missing data imputed by multiple imputation carrying forward the baseline value and adding the error term, with treatment, region, sex, and age group as fixed factors, and baseline HbA1c as covariate.
    In Study J, there were 2.9% of subjects in Insulin Degludec and 6.3% Insulin detemir arms for whom data was missing at the 26-week HbA1c measurement.
A total of 24 sessions of breathing exercises and high-repetitive muscle endurance and strengthening exercises will be applied to the pulmonary telerehabilitation group for 8 weeks, two days a week and one day a week unsupervised, via online systems. High-repetition muscle endurance and strengthening exercises will be applied to large muscle groups of the lower and upper extremities by creating resistance with body weight and theraband.
Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a two-arm, two-stage randomized trial of 320 adult PWH who smoke cigarettes and receive care in one of three health systems (targeted enrollment changed from 632 to 320 with NCI approval and IRB protocol amendment). At inception, participants will be randomized to either combination nicotine replacement therapy (NRT, patch + short-acting NRT) or combination NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed by exhaled carbon monoxide \[eCO\] or collateral verification) in both arms will receive 12 more weeks of the same treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with medication switch to oral medication, varenicline or bupropion, or intensified level of CM (start CM if no CM during first 12 weeks, or CM with higher reward schedule \["CM plus"\] if NRT+CM group initially). The intervention will be delivered by trained clinical pharmacists. The primary outcomes will be self-reported reduction in average cigarettes smoked per day at 24 weeks and 12 weeks (primary outcome changed from eCO-confirmed abstinence to self-reported abstinence with NCI approval and IRB protocol amendment). The specific aims of the proposed study are to: (1) identify the optimal adaptive approach to promote reduced tobacco use (changed from eCO-confirmed smoking abstinence with NCI approval and protocol amendment) (2) study the effectiveness of various adaptive strategies on CD4 count, HIV viral suppression, and VACS index (validated measure of morbidity and mortality risk); and (3) grounded in implementation science and using aHybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.
This group will receive a single dose of ICG, infused over 40 minutes. During surgery, they will be imaged with a camera and an imaging probe the investigators have developed.
The primary objective of the MILED trial is to determine if early, long term (2 yr), low dose (fixed at 1 mg/day) treatment of patients with well-preserved lung function will prevent disease progression to more advanced stages. Sixty patients with FEV1\>70% predicted will be enrolled and randomized to receive 1 mg/day sirolimus or placebo, and followed for a period of 2 years with pulmonary function testing every 4 months. The primary endpoint will be the between-group (placebo vs. sirolimus) difference in the rate of change in FEV1 (in liters) over two years. Secondary endpoints will include severity grade adverse events, time to 200cc or 10% FEV1 decline, forced vital capacity, lung volumes, diffusing capacity, serum VEGF-D, and early airflow obstruction assessed using hyper-polarized gas MRI. The study will be conducted through the Rare Lung Disease Clinic Network, a confederacy of clinics organized by the LAM Foundation that is currently following over 1300 U.S. LAM patients and conducting the Department of Defense sponsored Trial of an Aromatase Inhibitor in LAM (TRAIL) trial. The LAM Foundation will assist with study recruitment and dissemination of results, and the University of South Florida will function as the Data Coordinating Center. Successful completion of this study will define the safety and efficacy of low dose sirolimus in patients with normal lung function, and determine if sirolimus can be used to prevent disease progression to symptomatic stages.
The current diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD) foresee a relative sparing of long-term memory. Although bvFTD patients were thought to report secondary memory deficits associated with prefrontal dysfunctions, some studies indicated the presence of a "genuine memory deficit" related to mesial temporal lobe dysfunctions. Among various neuropsychological tests, the Free and Cue Selective Reminding Test (FCSRT) has been recommended to distinguish genuine from apparent amnesia. We conducted a systematic review and a random effect Bayesian meta-analysis to evaluate the nature and severity of memory deficit in bvFTD. Our objective was to determine whether the existing literature offers evidence of genuine or apparent amnesia in patients with bvFTD, as assessed via the FCSRT. On 06/19/2021, we conducted a search across four databases (PMC, Scopus, Web of Science, and PubMed). We included all studies that evaluated memory performance using the FCSRT in patients with bvFTD, as long as they also included either cognitively unimpaired participants or AD groups. We tested publication bias through the Funnel plot and Egger's test. To assess the quality of studies, we used the Newcastle-Ottawa quality assessment scale adapted for cross-sectional studies. We included 16 studies in the meta-analysis. The results showed that bvFTD patients perform better than AD patients (pooled effects between 0.95 and 1.14), as their memory performance stands between AD and control groups (pooled effects between - 2.19 and - 1.25). Moreover, patients with bvFTD present both genuine and secondary memory disorders. As a major limitation of this study, due to our adoption of a rigorous methodology and stringent inclusion criteria, we ended up with just 16 studies. Nonetheless, our robust findings can contribute to the ongoing discussion on international consensus criteria for bvFTD and the selection of appropriate neuropsychological tools to facilitate the differential diagnosis between AD and bvFTD.