anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).
BACKGROUND: Early-life exposure increases health risks throughout an individual's lifetime. Biological aging is influenced by early-life risks as a key process of disease development, but whether early-life risks could accelerate biological aging and elevate late-life mortality and morbidity risks remains unknown. Knowledge is also limited on the potential moderating role of healthy lifestyle.
METHODS: We investigate associations of three early-life risks around birth, breastfeeding, maternal smoking and birth weight, with biological aging of 202 580 UK Biobank participants (54.9 ± 8.1 years old). Biological aging was quantified as KDM-BA, PhenoAge and frailty. Moderate alcohol intake, no current smoking, healthy diet, BMI <30 kg/m2 and regular physical activity were considered as healthy lifestyles. Mortality and morbidity data were retrieved from health records.
RESULTS: Individual early-life risk factors were robustly associated with accelerated biological aging. A one-unit increase in the 'early-life risk score' integrating the three factors was associated with 0.060 (SE=0.0019) and 0.036-unit (SE = 0.0027) increase in z-scored KDM-BA acceleration and PhenoAge acceleration, respectively, and with 22.3% higher odds (95% CI: 1.185-1.262) of frailty. Increased chronological age and healthy lifestyles could mitigate the accelerations of KDM-BA and PhenoAge, respectively. Associations of early-life risk score with late-life mortality and morbidity were mediated by biological aging (proportions: 5.66-43.12%). KDM-BA and PhenoAge accelerations could significantly mediate the impact on most outcomes except anxiety, and frailty could not mediate the impact on T2D.
CONCLUSION: Biological aging could capture and mediate the late-life health risks stemming from the early-life risks, and could be potentially targeted for healthy longevity promotion.
Patients in this arm will receive a low literacy smoking cessation educational brochure and a list of hospital and community resources for smoking cessation. Patients will also receive navigation from a trained navigator Patients will receive up to 4 hours of patient navigation, in person or over the phone, over a 3-month period.
Systemic sclerosis or scleroderma is a multisystemic disorder characterized by the excessive synthesis and deposition of extracellular matrix proteins that result in the fibrosis of skin and visceral organs (including gastrointestinal tract, lungs, heart and kidneys).The pathogenesis of scleroderma is complex and still poorly understood, but major pathways involved in the development of the condition are microvascular and immunological abnormalities, as well as dysregulation of fibroblast activity. One of the key molecules involved in the pathogenesis of skin fibrosis is the TGF-beta1; TGF-beta1 is a cytokine directly responsible for fibroblasts proliferation and collagen and extracellular matrix overproduction. The affected skin of patients with systemic sclerosis gradually becomes firm, thickened and eventually tightly bound to underlying subcutaneous tissue (indurative phase). It loses hair, oil, and sweat glands becoming dry and coarse. Changes begin distally in the extremities and advance proximally. Lesions develop over a period of time varying from months to a few years. In patients with limited scleroderma, only the skin of fingers, hands, face and lower arms and legs are affected. On the contrary, patients with the diffuse cutaneous disease, skin changes will become generalized, involving initially the extremities and followed by the face and trunk. Rapid progression of these changes over a 2 to 3 year period is usually associated with a greater risk of visceral disease. After several years of disease, the skin may soften and return to normal thickness or become thin and atrophic. The EMEA and FDA have granted P144 the orphan drug status for the treatment of systemic sclerosis. The primary objective is to assess the long-term safety of P144 crem topically administered in skin manifestations of systemic sclerosis patients in terms of the incidence of treatment related adverse events during the extension period of six months.
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery.
MATERIALS AND METHODS: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves.
RESULTS: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973.
CONCLUSIONS: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.
Each participant exercised twice weekly for 10 weeks on the Gamebike® but the games and controls were turned off. The Gamebike® was used by both groups to control for any differences between two cycle ergometers such as comfort or usability. However, participants were allowed to listen to music of their choice via radio, CD or personal music device.
PURPOSE: A composition for enhancing elasticity and wrinkle improvement which contains onion, comfrey, ecliptae herba and cacao extract is provided to increase collagen production and to suppress the activation of collagenase. CONSTITUTION: A composition for enhancing elasticity and wrinkle improvement contains onion, comfrey, ecliptae herba and cacao extract as active ingredients. The onion extract and ecliptae herba extract are contained at the mass rate of 1-10 : 1-10. A cosmetic composition for enhancing elasticity and wrinkle improvement contains onion extract, Ecliptae Herba extract and Symphytum officinale extract as the active ingredient. The onion extract, Ecliptae herba extract, and comfrey extract are contained at the mass rate of 1-10 : 1-10 : 1-10. The extract is extracted as C1-C3 of alcohol, water, or a mixture thereof. [Reference numerals] (AA) Biosynthesis amount of collagen; (BB) Biosynthesis rate of collagen(%); (C1~12) Embodiment 1-12; (DD) Retinoic acid; (EE) Negative control group; (FF) Sample
PURPOSE:To produce a novel antibiotic substance zofimarin having antimicrobial activity against fungi and obtain an antimicrobial agent containing the antibiotic substance zofimarin as an active constituent, by cultivating a microorganism, belonging to the genus Zopfiella and capable of producing the zofimarin. CONSTITUTION:An ascomycete belonging to the genus Zopfiella, e.g. Zopfiella marina, is cultivated. The cultivation is carried out according to general fungi, but artifical seawater is used in place of tap water in a liquid culture medium. A carbon source, nitrogen source, inorganic salt, etc., are added, and a defoaming agent is suitably used to carry out the cultivation at 20-30 deg.C by the spinner culture method with aeration. After completing the cultivation, microbial cells are removed, and the resultant product in the supernatant liquid or filtrate is extracted and purified to afford the aimed zofimarin. The above- mentioned antibiotic substance is neutral colorless oily substance exhibiting the following properties; Soluble in methanol, ethanol and acetone and slightly soluble in water. Positive to the color reaction with iodine and sulfuric acid, etc., and expressed by the formula.
BACKGROUND Reye syndrome is a rare, yet potentially life-threatening disease characterized by acute encephalopathy and hepatic failure. This report presents the case of an 8-year-old girl with Reye syndrome and seizures after the use of naproxen. CASE REPORT An 8-year-old girl experienced a 3-day episode of fever and abdominal pain. After receiving naproxen (375 mg twice daily) starting from day -3, she exhibited hypotension, tonic seizure, and loss of consciousness (day 1). Physical examination and laboratory test results revealed acute kidney injury, metabolic acidosis, and elevated levels of lactate dehydrogenase (LDH), liver enzymes, and ferritin. On day 2, the maximum values of aspartate aminotransferase, alanine aminotransferase, LDH, creatinine, and ferritin were 955 U/L, 132 U/L, 8040 U/L, 2 mg/dL, and >40000 ug/L, respectively. She was given supportive care and recovered after 11 days (day 12), with normalization of kidney function and metabolic abnormalities. To identify possible genetic polymorphisms associated with the patient's symptoms, genotypes were tested using a drug metabolizing enzymes and transporters (DMET) gene chip. Among genes involved in the metabolism of naproxen, UGT1A6 (*1/*2) and UGT2B7 (*1/*2) resulted in possibly decreased function. Other results which may have had clinical significance included homozygote results for NAT2*6/*6 (rs1799930). CONCLUSIONS A rare case of Reye syndrome after administration of naproxen was presented in this case. A DMET gene chip was used to screen for possible genetic polymorphisms associated with Reye syndrome, but the result was inconclusive.
Patients receive imatinib mesylate PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Bolus doses of midazolam (5 mg midazolam dissolved in 10 ml saline; 2 ml of the solution or 1 mg midazolam per bolus, premedication dose of 2mg, induction dose of 2 mg) and fentanyl (100 μg / 10 ml; 5 ml of the solution or 50 μg fentanyl per bolus, induction dose of 50μg) were administered at 20-minute intervals in between and titrated as needed to obtain the desired sedation depth. No more than 12 mg of midazolam and 150 μg of fentanyl were administered.
Automatic determination of underlying reasons for lack of treatment adherence is provided. In various embodiments, patient information for a patient is retrieved. The patient information comprises a treatment plan. A failure of compliance with the treatment plan by the patient is determined from the patient information. The failure of compliance and the patient information are evaluated to determine one or more potential cause of the failure of compliance. The one or more potential cause is provided to a user for review.
A protein purified from bovine colostral whey and isolated nucleotide sequences encoding the protein is identified. The isolated bovine protein is termed Bovine Lactation Associated Immunotropic (Bo-LAIT) protein. The human homologue of Bo-LAIT protein, Hu-LAIT protein, is also described. A method of activating B cells, and particularly of activating B cells in a mammal, such as a human, in need of such activation by administering LAIT protein is described. LAIT protein can be incorporated into infant formula. LAIT protein can be administered to an infant, as by feeding to the infant such formula. LAIT protein can be incorporated as part of a vaccination, LAIT protein can be administered to a patient having a T cell immune deficiency, for example, a particular T cell dysfunction in which gp39 (CD40L) is under expressed on or totally absent from the cell surface of patient T cells. Preparation of medicaments including LAIT protein for activating B cells in a mammal in need of such activation is described. Natural or recombinant LAIT protein can be used.
Solid mannitol of modified form is obtained by dissolution in a volatile solvent, spraying said solution as fine droplets into a stream of heated inert gas, removing the vaporized solvent and separating the dry mannitol particles. The solvent may contain one or more pharmaceutically acceptable film forming agents, e.g. a cellulose ether, a gum such as tragacanth, guar or accacia, a polymer e.g. polyvinyl pyrrolidone, polyvinyl alcohol, or polivinyl acetate, gelatin, a wax or waxy substance e.g. stearic acid, cetyl alcohol, hydrogenated castor oil, or carnuba wax. It is preferred to heat the gas to a temperature above the boiling point of the solvent, especially above 100 DEG C., and to employ a suspension of mannitol in a saturated solution thereof.  The use of chloroform and water as the volatile solvent is illustrated in the examples, which also include the various film forming agents. The modified mannitol may be used as an excipient in pharmaceutical tablet compositions (see Division A5). A number of suitable formulations of which are given.ALSO:The use, as excipient, of spray dried mannitol (see Division C2) with optionally incorporated pharmaceutically acceptable film - forming agents, e.g. cellulose ethers, guar gum, tragacanth or accacia, polyvinyl pyrrolidone, acetate or alcohol, gelatin or waxes such as stearic acid, cetyl alcohol, carnauba, hydrogenated castor oil, having improved flow and compression characteristics is illustrated in compositions for tableting.  Examples are given for compositions containing: (a) Folic acid, (b) Ascorbic acid, (c) Phenobarbital, (d) Riboflavin, (e) Pentaerythrityl Tetranitrate, (f) Aspirin, (g) Niacinamide, (h) Phenelzine, (i) Dextromethorphan.
Provided is a gene expression control method that employs a transcription termination sequence positioned within an intron. The transcription termination sequence is disruptable by the addition of a trans-acting factor. For example, in a 'dual splicing switch', the transcription termination sequence is flanked by recombination sites and can be excised by a recombinase. The Cre/LoxP recombination system may be used for this purpose. In use, the intron containing the disruptable transcription termination sequence is positioned within a reading frame of a target gene. Also provided is a nucleic acid containing this transcription control mechanism and a cell line harboring a gene containing the nucleic acid. In one example, the transcription control mechanism is used to produce a cell line containing a toxic gene, the AAV Rep gene. A cell line for producing recombinant AAV virus particles, or recombinant parvovirus particles, also is provided along with a method for producing the same.
Patients receiving PRISTIQ should have regular monitoring of blood pressure since increases in blood pressure were observed in clinical studies. Pre-existing hypertension should be controlled before initiating treatment with PRISTIQ. Caution should be exercised in treating patients with pre-existing hypertension or other underlying conditions that might be compromised by increases in blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported with PRISTIQ. 

###  Sustained hypertension

Sustained blood pressure increases could have adverse consequences. For patients who experience a sustained increase in blood pressure while receiving PRISTIQ, either dose reduction or discontinuation should be considered [see Adverse Reactions (6.1)]. Treatment with PRISTIQ at all doses from 50 mg/day to 400 mg/day in controlled studies was associated with sustained hypertension, defined as treatment-emergent supine diastolic blood pressure (SDBP) ≥ 90 mm Hg and ≥ 10 mm Hg above baseline for 3 consecutive on-therapy visits (see Table 2). Analyses of patients in PRISTIQ controlled studies who met criteria for sustained hypertension revealed a consistent increase in the proportion of patients who developed sustained hypertension. This was seen at all doses with a suggestion of a higher rate at 400 mg/day.
At baseline, subjects underwent an OGTT and 72 hr of out-patient continuous glucose monitoring. They were treated with acarbose (50 mg with meals three times daily) for 6 weeks and repeat 72 hr CGMS profiles were obtained at the end of the study.
BACKGROUND: Current guidelines recommend maintaining a resting heart rate below 100-110 beats per minute (bpm) for patients with atrial fibrillation (AF). However, there is a lack of research on various treatment approaches for patients with both atrial fibrillation and coronary heart disease (AF&CHD). We have discussed the primary therapeutic options for controlling resting heart rate in patients with AF&CHD.
METHODS: We conducted a post hoc analysis of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. Our study included 3986(98.2%) participants with AF, of which 1522 had AF&CHD. The primary outcome was all-cause mortality. We utilized the chi-squared test to identify significant differences in categorical variables. Multivariate Cox regression analysis was performed to compare the risk of death by standard deviation of heart rate visit to visit variability quartile.
RESULTS: Compared to the AF group, a higher proportion of patients in the AF&CHD group had histories of smoking, hypertension, diabetes, heart failure, cardiomyopathy, valvular heart disease, peripheral vascular disease, bradycardia, hepatic or renal disease, pulmonary disease, and stroke (all P < 0.001). Additionally, patients with AF&CHD were more likely to undergo coronary artery bypass grafting (CABG) and pacemaker surgeries than those with AF alone. After adjusting for multiple clinical variables, patients with AF&CHD had a significantly higher risk of all-cause mortality compared to the AF group (RR = 1.79, 95% CI: 1.49-2.60; P < 0.01). Nonlinear multivariate curve-fitting analysis identified an optimal resting heart rate of 70 bpm for patients with AF&CHD (P < 0.001). Subgroup analysis revealed that patients with a resting heart rate below 70 bpm had lower all-cause mortality than those with a resting heart rate above 70 bpm (P < 0.001).
CONCLUSIONS: For resting heart rates below 70 bpm, our results suggest an inverse causal relationship between genetically determined resting heart rate and all-cause mortality in patients with AF&CHD.
CLINICAL TRIAL NUMBER: Not applicable.
Participants will receive MNTX 24 mg as an IV infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant).
Fluorescent dyes in the form of 4-dimethylaminophenylvinyl-1-sulfanylalkyl-pyridinium salts are new. Fluorescent dyes of formula (I) are new (and their salts, optical isomers, geometrical isomers or solvates such as hydrates). An : anionic counter-ion; Y : alkali or alkaline earth metal, optionally substituted ammonium or phosphonium, or a protective group for thiol functions. If (I) contains other cationic parts, these will be associated with one or more anions so as to achieve electrical neutrality. Independent claims are also included for (1) coloring compositions containing (I) in a cosmetically-acceptable medium (2) coloring compositions containing (I) and reducing agent(s) in a cosmetically-acceptable medium (3) a method for coloring keratin fibres by treatment with compositions containing (I) or the corresponding unprotected thiol (II) (4) a multi-compartment device in which one compartment contains a composition containing (I) and a second compartment contains a reducing agent capable of reducing the disulfide bonds in keratinous materials. [Image].
Measurement of middle-ear muscle reflexes (MEMR) constitutes an important component of the standard of care in auditory function assessment and diagnostic audiology. An important component of the middle-ear test battery involves characterizing neural function through the eighth nerve-brainstem pathway which is accomplished through measurement of the MEMR. The evaluation component of this project will involve testing of human subjects using wideband acoustic immittance in the evaluation of middle-ear muscle reflexes. Subjects in this project will be infants, children and adults with normal hearing as well as with conductive, sensory, and neural hearing loss. All subjects will receive wideband acoustic immittance (WAI) and middle-ear muscle reflex (MEMR) testing. Baseline testing includes pure tone audiometry and otoacoustic emissions.
The wound will be treated with a silver antimicrobial dressing appropriate for the exudate level as per manufacturer instructions for use for 2 weeks +/- 3 days, in addition to any necessary standard care (e.g. compression for a venous leg wound).
BACKGROUND: In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk.
METHODS: As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS).
RESULTS AND CONCLUSIONS: We used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10-6) in our study.