anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
There was no evidence of a tumorigenic effect when Lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day (about 56 or 9 times* the maximum recommended daily human dose, based on body weight and body surface area, respectively). There was no evidence of carcinogenicity when Lisinopril was administered for 92 weeks to (male and female) mice at doses up to 135 mg per kg per day (about 84 times* the maximum recommended daily human dose). This dose was 6.8 times the maximum human dose based on body surface area in mice.

Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, Lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg per kg per day of Lisinopril. This dose is 188 times and 30 times the maximum human dose when based on mg/kg and mg/m2, respectively.

Studies in rats indicate that Lisinopril crosses the blood brain barrier poorly. Multiple doses of Lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C Lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.

*Calculations assume a human weight of 50 kg and human body surface area of 1.62 m2
Subjects will exercise at a moderate intensity for 60 minutes. There are no different arms in this study.
In a pharmacokinetic study, male and female subjects 18 years of age or older with acne vulgaris (N=30) applied approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 21 days. The mean ± SD C maxand AUC 0-24hwere 1.3 ± 0.6 ng/mL and 23.0 ± 10.8 ng·h/mL, respectively at Day 21 for AMZEEQ. After daily application of AMZEEQ in subjects with acne for 21 days, steady-state was reached by Day 6 and systemic accumulation of minocycline was not evident. 

Specific Populations

Age: Pediatric Population

Pharmacokinetics of minocycline was evaluated in 20 subjects 10 years to less than 17 years of age with acne vulgaris following application of approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 7 days. Minocycline was detected in all samples obtained on Day 7. Pharmacokinetic results are presented by age group in Table 2. The overall pediatric population showed 2.4-fold and 2.7-fold higher C maxand AUC 0-24hcompared to the adult population.
INTRODUCTION: Lower extremity (LE) reconstruction in the elderly population presents a multifaceted challenge, primarily due to age-related degenerative changes, comorbidities, and functional decline. Elderly individuals often encounter conditions such as osteoarthritis, osteoporosis, and cardiovascular and peripheral artery disease (PAD), which can severely compromise the structural integrity and function of the lower limbs. As such, we aim to assess postoperative complications and functional recovery following LE reconstruction in elderly patients.
METHODS: Patients ≥ 18 years who underwent post-traumatic LE reconstruction with flap reconstruction at a Level 1 trauma center between 2007 and 2022 were included. Patient demographics, flap/wound characteristics, complications, and ambulation for the elderly (≥ 60 years old) and the control (< 60 years old) cohorts were recorded. The primary outcome was final ambulation status, modeled with logistic regression. Secondary outcomes included postoperative complications.
RESULTS: The mean ages of the control (n = 374) and elderly (n = 49) groups were 37.4 ± 12.6 and 65.8 ± 5.1 years, respectively. Elderly patients more frequently required amputation after flap surgery (p = 0.002). There was no significant difference between the two cohorts in preoperative ambulation status (p = 0.053). Postoperatively, 22.4% of elderly patients were independently ambulatory at final follow-up, compared to 49.5% of patients < 60. Of the elderly, 14.3% could ambulate with an assistance device (cane, walker, etc.), compared to 26.5% in the control group. A wheelchair was required for 46.9% of elderly patients, significantly higher than the 22.7% of those < 60 years of age (p < 0.001). Multivariate regression confirmed an association between older age and nonambulatory final status (p = 0.033).
CONCLUSION: LE reconstruction can likely be performed safely in patients 60 years of age or older. However, older age is independently associated with significantly worse postoperative ambulation. Preoperative assessment, including gait and muscle strength, and early initiation of postoperative rehabilitation can potentially improve ambulation in elderly individuals undergoing LE reconstruction.
AIMS: Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM.
METHODS AND RESULTS: Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05).
CONCLUSION: We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.
Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.
We hypothesize that smoking cessation counseling improves with the implementation of a smoking status assessment data sheet in routine consults. This is a quality improvement study design to evaluate the impact of the implementation of a more formal smoking status evaluation in a resident/faculty driven outpatient clinic. This will be an observational study in which differences in quality measures will be compared between baseline and re-measurement periods. Population target: 900 patients screened before and after the implementation of the QI intervention. Primary outcome: smoking status evaluation. Secondary Outcome: number of patients advised to quit, plan implementation for smoking cessation, smoking cessation program referrals, number of NRT and bupropion prescription.
INTRODUCTION: The last decade has seen the increased prevalence of obesity as a public health challenge, particularly in low- and middle-income countries. At the same time, studies have shown that there is a two-way relationship between low-calorie diets and depression in obese individuals. This study was designed and implemented to investigate the effect of a low-calorie high-protein diet on psychometric variables in obese individuals.
MATERIALS AND METHODS: The present study is a Randomized Clinical Trial. Individuals meeting the inclusion criteria were randomly assigned to either the intervention group (low-calorie diet with increased protein percentage) or the control group (standard protein percentage) using block stratification. Psychometric characteristics of the participants were evaluated using the DASS-21 questionnaire.
RESULTS: There were no significant differences in enrollment between the two groups with respect to anthropometric variables, body composition, and physical activity (p-value > .05). Similarly, no significant differences were observed between the two groups in terms of psychological variables (depression, anxiety and stress) (p-value > .05). However, the intervention groups had significantly lower depression and anxiety scores 15 days into the intervention (p-value < .05). After 30 and 60 days of intervention, significant differences were observed between the 2 groups in terms of depression, stress, and anxiety (p-value < .05), indicating a relative improvement in psychometric variables in the intervention group (p-value < .05).
CONCLUSION: The results of this study showed that low-calorie diets with a high-protein percentage can significantly improve psychometric variables in obese people.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20221101056371N1..
In the intervention group the HemoSphere screen is visible and the anesthesiologist and PACU personal are instructed to follow the algorithm (chapter 4) in case of a HPI \>85%. The purpose of the alarm at 85% and the presented algorithm is to prevent hypotension. If hypotension occurs, it should be treated as according to the standard of care.
Clinical studies of hydrocodone bitartrate 5 mg and acetaminophen 500 mg did not include sufficient numbers of subjects aged 65and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identifieddifferences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious,usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, andof concomitant disease or other drug therapy.Hydrocodone and the major metabolites of acetaminophen are known to be substantially excreted by the kidney. Thus the risk of toxicreactions may be greater in patients with impaired renal function due to the accumulation of the parent compound and/or metabolites page 4 of 7 in the plasma. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and itmay be useful to monitor renal function.Hydrocodone may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses ofhydrocodone bitartrate and acetaminophen tablets and observed closely.ADVERSE REACTIONSThe most frequently reported adverse reactions are lightheadedness, dizziness, sedation, nausea and vomiting. These effects seem tobe more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patientlies down.Other adverse reactions include:Central Nervous System: Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear,dysphoria, psychic
Group 1 Pre-trained group will receive information on how to optimally perform the ORSI chicken anastomosis task and the material will be delivered online via the ORSI e-learning platform. They will be given access to the material two weeks before their training. Unlike the other groups, Group 1 will be required to study the material to a pre-defined performance benchmark or proficiency level. Once the online course is completed, participants have to perform the orsi chicken anastomosis task.
BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T.
METHODS: In this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes.
RESULTS: Among the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS.
CONCLUSION: Patients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy.
All participants will receive Fasenra® 30 mg Q8W + high-dose Symbicort® maintenance ×2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible participants randomised to the reference arm will continue on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment for 32 weeks.
This is a randomized double-blind placebo-controlled clinical trial evaluating the effect of 500 mg valacyclovir twice daily on HCV viral load in HSV-1/HCV co-infected patients seronegative for HSV-2. Potential participants will be recruited from the Jackson VAMC viral hepatitis clinics. Eligible individuals will be invited to enroll in the study in a noncoercive manner. Study personnel will obtain full informed consent.

Using a computer generation randomization scheme, patients will be randomized 1:1 in blocks of 4 to receive valacyclovir 500 mg po twice daily or matching placebo. Patients will be counseled on the signs and symptoms of herpes labialis and genital herpes and complete a questionnaire to document medical/social history. Venipuncture will be performed every four weeks (i.e., at every other follow-up visit) to monitor complete blood cell count, liver function tests, serum levels of hepatitis C RNA and Herpeselect IgG HSV-2 ELISA. A de-identified baseline serum sample will be collected and stored in VA approved research space for future testing. At each visit, pill-count and tolerability of medications will be assessed. Patients will be asked about signs or symptoms of genital herpes. Data will be kept in a study chart labeled with the participant's coded study number in a locked office. Information from each study visit will be recorded into the chart by the PI or RA and entered into an encrypted database on a secure VA server. Baseline characteristics of the placebo and intervention group will be compared using appropriate parametric tests. HCV viral loads will be log10 transformed and analyzed using an intention to treat model.
This study is designed to assess whether increasing the consumption of natural food folates from a mixed diet is as effective as supplemental folic acid or supplemental natural folate in raising folate status, reducing biomarkers of cardio vascular disease (CVD) risk, and improving vascular function. Randomised placebo-controlled parallel studies will be undertaken in groups of individuals in Norwich and Sheffield. There will be four treatment arms: a) 200 µg folate per day from folate-rich foods, b) 200 µg folate per day from supplemental folic acid, c) 200 µg folate per day from supplemental Metafolin® (6S 5-methyltetrahydrofolic acid) and d) a placebo group. Results from the two centres will be combined, thus ensuring a wide population is covered. Folate status, biomarkers of CVD risk and vascular function (pulse wave velocity) will be measured before and following the intervention period of 16 weeks, together with possible confounders (such as vitamins B2 \& B12 status, and MTHFR genotype). 7-Day weighed intakes will be used to measure habitual B-vitamin intake during baseline and intervention, to determine changes in folate intake and assist compliance. Additionally, folate content of selected folate-rich foods will be determined for each volunteer. The results will aid the Food Standards Agency (FSA) in formulating public health policy related to improving folate status and reducing CVD risk.
INTRODUCTION AND HYPOTHESIS: Identifying the factors influencing the development of female urinary incontinence (UI) may facilitate early intervention, potentially delaying its progression. This study was aimed at investigating the impact of lifestyle habits on the severity of UI among women in East China.
METHODS: This study included 414 women from six communities in East China who reported symptoms of UI and was conducted between September and December 2020. Data were collected using a general information questionnaire, the Toileting Behaviours: Women's Elimination Behaviours scale, and the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form Chinese Version. Participants were categorised into two groups: those with mild UI and those with moderate-to-severe UI. Propensity-score matching was performed to balance confounding factors, and logistic regression was used to explore the relationship between lifestyle behaviours and UI severity.
RESULTS: A total of 117 pairs were successfully matched. Logistic regression analysis revealed that daily perineal cleaning significantly protected against moderate-to-severe UI (p < 0.05). Conversely, living alone, poor sleep quality and hovering over the toilet while voiding were identified as independent risk factors for moderate-to-severe UI (p < 0.05).
CONCLUSION: Several lifestyle habits significantly impact the severity of UI among adult women. Screening for mild urinary leakage symptoms and implementing timely interventions are crucial for preventing the aggravation of UI and improving ability to work and quality of life.
CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.
A method for manufacturing a skin care composition may include blending a first phase of the skin care composition. The first phase of the skin care composition may include a predetermined percentage of water, between about 2% and 20% by weight glycerin and/or diglycerin, and between about 0.1% and 5% by weight of an emulsifier. The method may also include heating the first phase to a first predetermined temperature. The method may further include blending a second phase of the skin care composition. The second phase of the skin care composition may include between about 2% to 20% by weight grapeseed oil, between about 2% to 30% by weight stearic acid, between about 0.5% and 5% by weight shea butter, between about 0.5% to 5% by weight beeswax and/or synthetic beeswax, between about 0.5% to 2% by weight cetyl alcohol, and between about 0.5% to 5% by weight essential oil. The method may still further include heating the second phase to a second predetermined temperature, blending the first phase at the first predetermined temperature to the second phase at second predetermined temperature, and cooling the blended first and second phase to a third predetermined temperature. All weights are based on a total weight of the composition.