anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Background: Urethral stricture disease is a common and at times unsatisfying condition that can lead to complications severely impacting a patient's quality of life (QOL). Open urethroplasty remains the gold standard treatment, however it is an invasive and highly specialized procedure. Strictures between 2 and 4 cm in length have been shown to recur at a rate of 50% within 12 months, a rate that typically decreases with each subsequent treatment. The Laborie Optilume drug-coated balloon (DCB) is the first of its kind developed for adjunct treatment of urethral strictures in men. The DCB initially treats the stricture through balloon dilatation and subsequently aims to prevent recurrence via the localized application of Paclitaxel. Our study assesses the safety and efficacy of the DCB in an Australian population with strictures exceeding 2 cm, who have undergone at least two prior procedures for urethral stricture disease. Methods: Patients were prospectively recruited from November 2019 to September 2021. International prostate symptom score (IPSS), IPSS QOL, and voiding parameters were collected at baseline, and again at 1, 6, 12, and 18 months. The DCB was applied by a single consultant urologist under rigid cystoscope with shallow direct vision internal urethrotomy with a cold knife prior to application of the DCB. Results: Seventeen patients were recruited with an average of 7.7 prior urethral procedures for recurrent stricture disease. In total, 76% were stricture free at 30 months follow-up. There were improvements in almost all parameters including max flow, average flow, IPSS, and IPSS QOL scores at 12 and 24 months. There were no complications. Conclusion: The DCB is a safe and effective method at reducing the rates of recurrence for high-risk stricture disease and can delay or prevent the need for urethroplasty in what remains a very challenging cohort of patients.
To achieve maximum contraceptive effectiveness, take one ODT every day at about the same time each day. Place one ODT on the tongue, allow to disintegrate and then follow with 8 oz. (240 mL) of water. The recommended dosage of FEMLYV is one ODT daily for 28 consecutive days: one green active ODT daily during the first 24 days followed by one white inert ODT daily during the 4 following days (see Table 1). FEMLYV must be taken in the order directed on the blister pack. ODTs should not be skipped or taken at intervals exceeding 24 hours. FEMLYV may be administered without regard to meals [see 12.3]. Instruct the patient to begin taking FEMLYV either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).
Synthetic promoters may be designed using short cis-regulatory elements (CREs) and core promoter sequences for specific purposes. We identified novel conserved DNA motifs from the promoter sequences of leaf palisade and vascular cell type-specific expressed genes in water-deficit stressed poplar (Populus tremula × Populus alba), collected through low-input RNA-seq analysis using laser capture microdissection. Hexamerized sequences of four conserved 20-base motifs were inserted into each synthetic promoter construct. Two of these synthetic promoters (Syn2 and Syn3) induced GFP in transformed poplar mesophyll protoplasts incubated in 0.5 M mannitol solution. To identify effect of length and sequence from a valuable 20 base motif, 5' and 3' regions from a basic sequence (GTTAACTTCAGGGCCTGTGG) of Syn3 were hexamerized to generate two shorter synthetic promoters, Syn3-10b-1 (5': GTTAACTTCA) and Syn3-10b-2 (3': GGGCCTGTGG). These promoters' activities were compared with Syn3 in plants. Syn3 and Syn3-10b-1 were specifically induced in transient agroinfiltrated Nicotiana benthamiana leaves in water cessation for 3 days. In stable transgenic poplar, Syn3 presented as a constitutive promoter but had the highest activity in leaves. Syn3-10b-1 had stronger induction in green tissues under water-deficit stress conditions than mock control. Therefore, a synthetic promoter containing the 5' sequence of Syn3 endowed both tissue-specificity and water-deficit inducibility in transgenic poplar, whereas the 3' sequence did not. Consequently, we have added two new synthetic promoters to the poplar engineering toolkit: Syn3-10b-1, a green tissue-specific and water-deficit stress-induced promoter, and Syn3, a green tissue-preferential constitutive promoter.
Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood. Here, we identified the secreted-type pro-fibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), as a brown adipose tissue (BAT)-derived adipokine that promotes liver fibrosis in a murine obesity-induced MASH model. BAT-specific or systemic PCPE-1 depletion in mice ameliorated liver fibrosis, whereas, PCPE-1 gain of function in BAT enhanced hepatic fibrosis. High-calorie diet-induced ER stress increased PCPE-1 production in BAT through the activation of IRE-1/JNK/c-Fos/c-Jun signaling. Circulating PCPE-1 levels are increased in the plasma of MASH patients, suggesting a therapeutic possibility. In sum, our results uncover PCPE-1 as a novel systemic control factor of liver fibrosis.
BACKGROUND: Nepal is committed to achieving the Sustainable Development Goal (SDG) 2030 target 3.1 of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. Along with increasing access to health facility (HF)-based delivery services, improving HF readiness is critically important. The majority of births in Nepal are normal low-risk births and most of them take place in public HFs, as does the majority of maternal deaths. This study aims to assess changes in HF readiness in Nepal between 2015 and 2021, notably, if HF readiness for providing high-quality services for normal low-risk deliveries improved; if the functionality of basic emergency obstetric and neonatal care (BEmONC) services increased; and if infection prevention and control improved.
METHODS: Cross-sectional data from two nationally representative HF-based surveys in 2015 and 2021 were analyzed. This included 457 HFs in 2015 and 804 HFs in 2021, providing normal low-risk delivery services. Indices for HF readiness for normal low-risk delivery services, BEmONC service functionality, and infection prevention and control were computed. Independent sample T-test was used to measure changes over time. The results were stratified by public versus private HFs.
RESULTS: Despite a statistically significant increase in the overall HF readiness index for normal low-risk delivery services, from 37.9% in 2015 to 43.7%, in 2021, HF readiness in 2021 remained inadequate. The availability of trained providers, essential medicines for mothers, and basic equipment and supplies was high, while that of essential medicines for newborns was moderate; availability of delivery care guidelines was low. BEmONC service functionality did not improve and remained below five percent facility coverage at both time points. In private HFs, readiness for good quality obstetrical care was higher than in public HFs at both time points. The infection prevention and control index improved over time; however, facility coverage in 2021 remained below ten percent.
CONCLUSIONS: The slow progress and sub-optimal readiness for normal, low-risk deliveries and infection prevention and control, along with declining and low BEmONC service functionality in 2021 is reflective of poor quality of care and provides some proximate explanation for the moderately high maternal mortality and the stagnation of neonatal mortality in Nepal. To reach the SDG 2030 target of reducing maternal deaths, Nepal must hasten its efforts to strengthen supply chain systems to enhance the availability and utilization of essential medicines, equipment, and supplies, along with guidelines, to bolster the human resource capacity, and to implement mechanisms to monitor quality of care. In general, the capacity of local governments to deliver basic healthcare services needs to be increased.
Subjects assigned to sequence AB will receive a single 160 mg dose of the test product Sotalol (1 x 160 mg tablet) marked as A in the sequence in the period 1 and a single 160 mg dose of the reference product Sotalex (1 x 160 mg tablet) marked as B in the sequence in the period 2 . These treatments will be administered orally with approximately 200 mL of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.
Session 1: Participants will meet individually with a research assistant to discuss their type 2 risk, discuss benefits of engaging in 150 minutes of moderate-to-vigorous physical activity per week and set a physical activity goal. First 30 minutes of each subsequent session will be ideal care (as described above in the control group). Last 30 minutes of sessions 2-6, self-compassion condition participants will learn to apply self-compassion to their prediabetes experience and physical activity. Session 2: Introduction to self-compassion. Session 3: Yin and Yang of self-compassion. Session 4: Mindfulness. Session 5: Mindfulness and Resistance. Session 6: Meeting Difficult Emotions. Session 7: Embracing the Good. Session 8: Applying Self-compassion to Physical Activity and Moving Forward.
X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare developmental disease affecting body parts derived from the embryonal ectoderm. It is caused by a broad spectrum of mutations in the ectodysplasin A gene (EDA). The main symptoms of XLHED are hypo- or anhidrosis, oligo- or anodontia, and hypotrichosis. Current treatment options are limited to the management of disease symptoms and prevention of complications. Effective corrective treatment for XLHED remains a high unmet medical need. ER004 represents a first-in-class signaling protein replacement molecule designed for specific, high affinity binding to the endogenous EDA1 receptor (EDAR). The proposed mechanism of action of ER004 is the replacement of the missing EDA1 protein in patients with XLHED. The aim of this prospective, open-label, genotype-match controlled, multicenter Phase 2 trial is to confirm the efficacy and safety results for ER004 administered intra-amniotically in a larger cohort of subjects. The target population will consist of male XLHED fetuses/subjects with EDA mutation confirmed by genetic diagnosis of a mutation in one of the maternal EDA alleles and ultrasonographic diagnosis of a significantly reduced number of fetal tooth germs, or by documented direct genetic diagnosis of a hemizygous EDA mutation. In the main study phase, efficacy and safety of the treated subjects will be assessed up to 6 months of age and safety of the mothers will be assessed up to 1 month after delivery of the child. In long-term follow-up phase, efficacy and safety of the treated subjects will be assessed up to 5 years of age. Treated subjects sweating ability will be compared to an untreated relative from his family, when available, or from a matched controlled subject from a previous natural history.
Patient with insufficient effect from previous treatment estradiol gel 0.1% 1.5mg will be given HRT in the form of: Transdermal estradiol gel 0.1% 2.0mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.
In the control period, patients were given intravenous fluids at the discretion of the anesthesiologist based on institutional protocol using 250ml of crystalloids or 100ml of colloids based on central venous pressure (CVP) and mean arterial pressure (MAP) measurements. The aim was to keep the CVP ≥ 8mmHg and MAP ≥ 65mmHg. Fluid boluses were administered up to a total of 1000ml, if patients did not attain a MAP of \>65 mmHg, a vasopressor drug was administered.
The disclosure belongs to the field of biological medicine, and in particular relates to application of fullerene in preventing or treating altitude degradation. In particular, the present disclosure provides a use of a fullerene in the preparation of a composition for preventing or treating altitude degradation. Hypoxia results in reduced mice feeding, weight and physical performance, elevated blood oxidative stress levels, and increased metabolic waste lactate. Experimental results of the present disclosure demonstrate that changes in physical performance, oxidative stress, and lactic acid accumulation of mice caused by hypoxia can be improved by adding fullerenes to the mouse feed. Although the salidroside can also improve physical performance and reduce the degree of oxidative stress, the salidroside has no obvious effect of reducing accumulated lactic acid. Meanwhile, the medicine concentration of the salidroside is twice that of a high-concentration fullerene group, so that the treatment effect of the fullerene on the mice with the physical strength decline model is superior to that of the salidroside. In conclusion, the fullerene is a supplement with remarkable effect for improving exercise endurance, and can be widely used for preparing medicines for preventing and treating altitude degradation.
Participants will receive SHR-1316 intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) SHR-1316 until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
Neuroinflammation is intimately associated with poor prognosis in patients with subarachnoid hemorrhage (SAH). Alpha-lipoic acid (ALA), a disulfide antioxidant, has been shown to be neuroprotective in an in vivo model of neurological injury; however, the role of ALA in SAH has never been evaluated. In this study, the Sprague-Dawley rats SAH model was induced by endovascular perforation method. ALA was transplanted intravenously into rats, and SR-717, a stimulator of interferon genes (STING) agonist, was injected intraperitoneally. The effects of ALA on early brain injury were assayed by neurological score, hematoxylin and eosin staining and Nissl staining. Immunohistochemistry staining and Western blotting were used to analyze various proteins. ALA significantly reduced STING- NLRP3 protein expression and decreased cell death, which in turn mitigated the neurobehavioral dysfunction following SAH. Furthermore, coadministration of ALA and SR-717 promoted STING-NLRP3 signaling pathway activation following SAH, which reversed the inhibitory effect of ALA on STING-NLRP3 protein activation and increased the neurological deficits. In conclusion, ALA may be a promising therapeutic strategy for alleviating early brain injury after SAH.
The invention belongs to the chemical field and the medicine field, relates to and provides applications of harmol in preparation of antitumor drugs, and provides corresponding antitumor drug compositions. The invention also provides a method for inhibition of in vitro tumor cell proliferation. In the method, harmol is added in nutrient solutions of tumor cells. The tumor cells comprise liver cancer cells, stomach cells or leukemia cells. Harmol belongs to a natural product, and has minimal toxic and side effects, high bioavailability, stable properties and clinical use value. The low molecular weight compound can be developed as a new antitumor drug or an auxiliary component thereof, has obvious tumor suppression effects, is environmentally friendly, and provides a new way and method for treating and curing tumors.
PROBLEM TO BE SOLVED: To obtain the subject lotion capable of suppressing the activity of elastase and recovering and maintaining the tensity and elasticity of skin and thereby having effects on the prevention of skin aging and maintenance of a young skin state by formulating an extract from Ficus religiosa L. of the genus Ficus of the family Moraceae. SOLUTION: This skin lotion is obtained by formulating an extract from Ficus religiosa L. of the genus Ficus of the family Moraceae in an amount of preferably 0.0001-10.0 wt.% expressed in terms of a dried substance in the total amount of the lotion. The extract is preferably obtained by using a bark, dipping the bark in an extracting solvent (e.g. methanol or acetone) or refluxing the bark together with the extracting solvent under heating, then filtering and concentrating the extract solution. A bleaching ingredient, a humectant, an antioxidant, an oily ingredient, an ultraviolet light absorber, a sequestering agent such as disodium edetate, caffeine, vitamin C, magnesium ascorbate phosphate, etc., as necessary, can be formulated with the skin preparation for external use. The resultant skin lotion can preferably be applied to cosmetics.
PROBLEM TO BE SOLVED: To profitably obtain the subject compound useful as an intermediate for antitumor agents, etc., by successively reacting an acetopyruvic acid ester with an orthoformic acid ester and α-cyanoacetamide and subsequently reacting the reaction product with an acrylate ester. SOLUTION: This method for producing a dioxotetrahydroindolizine derivative comprises reacting a compound of formula I (R<1> is a 1-6C alkyl; R<2> is a 1-6C alkyl, an aryl, an aralkyl) (e.g. acetopyruvic acid ethyl ester) with an orthoformic acid ester in the presence of an acid catalyst (e.g. p-toluene sulfonic acid), reacting the obtained compound of formula II (R<3> a 1-6C alkyl, an aryl, an aralkyl) with α-cyanoacetamide in the presence of a base (e.g. potassium carbonate) in a polar solvent (e.g. dimethyl sulfoxide) and subsequently reacting the obtained compound of formula III with an acrylic acid ester. Thus, the objective dioxotetrahydroindolizine derivative of formula IV (R<4> is a 1-6C alkyl, an aryl, an aralkyl) is profitably obtained.
Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. Steady-state plasma concentrations are attained within 5 days of once per day dosing and exposure is approximately 1.6-fold greater than after a single dose. Mean tadalafil concentrations measured after the administration of a single oral dose of 20 mg and single and once daily multiple doses of 5 mg, from a separate study, ( see Figure 4) to healthy male subjects are depicted in Figure 4.   


Figure 4: Plasma tadalafil concentrations (mean ± SD) following a single 20-mg tadalafil dose and single and once daily multiple doses of 5 mg   
Absorption — After single oral-dose administration, the maximum observed plasma concentration (C max) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of Tadalafil following oral dosing has not been determined.   
The rate and extent of absorption of tadalafil are not influenced by food; thus tadalafil tablets may be taken with or without food.   
Distribution —The mean apparent volume of distribution following oral administration is approximately 63 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins.   
Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.   
Metabolism — Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10% of glucuronide concentrations. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations.   
Excretion —The mean oral clearance for tadalafil is 2.5 L/hr and the mean terminal half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).   
Geriatric — Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) with no effect on C max relative to that observed in healthy subjects 19 to 45 years of age. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered [ see Use in Specific Populations ( 8.5)].   
Patients with Diabetes Mellitus —In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure (AUC) was reduced approximately 19% and Cmax was 5% lower than that observed in healthy subjects. No dose adjustment is warranted.   
Patients with BPH — In patients with BPH following single and multiple-doses of 20 mg tadalafil, no statistically significant differences in exposure (AUC and Cmax) were observed between elderly (70 to 85 years) and younger (≤60 years of age) subjects. No dose adjustment is warranted.
A single blood volume leukapheresis for harvesting of PBMCs will be performed, As the transduced T cells will be frozen, the timing of leukapheresis is not defined \& can vary from patient to patient. Subsequently, a single dose of mesothelin-targeted T cells will be infused via intravenous catheter or central line (i.e., mediport). Patients will be monitored in the hospital and discharged home after a minimum of 48 hours. Patients will be monitored closely as outpatients for the next 2 months. Patients will be followed weekly as outpatients for the first 8 weeks after treatment. All patients will be hydrated intravenously, premedicated with acetaminophen \& diphenhydramine, \& administered cyclophosphamide at 1.5 g/m2 2 to 7 days (Day -7 to Day -2) before administration of mesothelin-targeted T cells.
Ongoing clinical trials are now evaluating the addition of bevacizumab to standard chemotherapeutic regimens for colorectal cancer such as FOLFOX or FOLFIRI. In these studies the addition of bevacizumab has been safe and has not resulted in significantly increased toxicity. Our proposed regimen has the advantage of being easily administered in the outpatient setting, with potential for enhanced activity and needs to be evaluated in a clinical trial.

The patterns of care for CRC have shifted, IFL previously the standard of care, is now proven to be an inferior regimen compared to FOLFOX4. (8) The recent FDA approval in February 2004 of bevacizumab for first line therapy, which states that bevacizumab is an approved agent in combination with a 5-FU regimen, gives no clear guidelines as to the "best regimen". This is an issue that needs to be evaluated rapidly in clinical trials, and it is clear that a combination of 5-FU or capecitabine with oxaliplatin and bevacizumab is one of the most active and well-tolerated regimens. The optimum sequence, schedule and doses needs to determined in clinical trials.
Participants in Groups 1-4 and Group 6 will receive a single dose of BAY2433334 on one occasion. Participants in Group 5 will receive a single dose of BAY2433334 on a dialysis-free day.