anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for example, against chronic myeloid leukemia. As a substrate of cytochrome P450 (CYP) 2C8, CYP3A4, and various transporters, imatinib is highly susceptible to drug-drug interactions (DDIs) when co-administered with corresponding perpetrator drugs. Additionally, imatinib and its main metabolite N-desmethyl imatinib (NDMI) act as inhibitors of CYP2C8, CYP2D6, and CYP3A4 affecting their own metabolism as well as the exposure of co-medications. This work presents the development of a parent-metabolite whole-body physiologically based pharmacokinetic (PBPK) model for imatinib and NDMI used for the investigation and prediction of different DDI scenarios centered around imatinib as both a victim and perpetrator drug. Model development was performed in PK-Sim® using a total of 60 plasma concentration-time profiles of imatinib and NDMI in healthy subjects and cancer patients. Metabolism of both compounds was integrated via CYP2C8 and CYP3A4, with imatinib additionally transported via P-glycoprotein. The subsequently developed DDI network demonstrated good predictive performance. DDIs involving imatinib and NDMI were simulated with perpetrator drugs rifampicin, ketoconazole, and gemfibrozil as well as victim drugs simvastatin and metoprolol. Overall, 12/12 predicted DDI area under the curve determined between first and last plasma concentration measurements (AUClast) ratios and 12/12 predicted DDI maximum plasma concentration (Cmax) ratios were within twofold of the respective observed ratios. Potential applications of the final model include model-informed drug development or the support of model-informed precision dosing.
Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.39 × 10-4) and 1.02 (95% CIs 1.01-1.03, P = 4.99 × 10-5) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.12 × 10-6) and 1.02 (95% CIs 1.01-1.02, P = 3.78 × 10-5) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01-1.03, P = 4.65 × 10-3), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P > 0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.
Provided are compositions and methods that include a K. pneumoniae yidR protein or an antigenic segment of the protein, and homologous of the protein, and antigenic segments of the homologs. The compositions can be provided as vaccine formulations for use with humans and non-human animals, including but not limited to dairy cows. The compositions and methods are useful for prophylaxis and/or therapy of conditions associated with Gram negative bacteria that include K. pneumonia, E. coli, and other pathogenic Gram negative bacteria. The conditions include such bacterial infections generally, and include specifically mastitis and metritis. The compositions and methods can also improve fertility and milk production. Administration of the compositions can improve the likelihood of a first service conception.
Primary hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by thickening (hypertrophy) of the left ventricular (LV) wall, dyspnea and/or fatigue in the setting of a normal or supra-normal LV ejection fraction. The specific mechanisms underlying heart failure-related symptomatology in non-obstructive HCM are poorly defined, but as the vast majority of HCM patients with heart failure have apparently preserved LV contractile function, their symptoms of dyspnea and fatigue are presumed due to perturbations of the relaxation/filling phase (diastole) of the cardiac cycle, which has been termed "diastolic dysfunction". In fact, diastole is mechanistically complex and involves LV pressure decay (relaxation), chamber compliance and atrial contractile function. LV end-diastolic volume, which represents fiber stretch, governs LV contractile function and stroke volume via the Frank-Starling mechanism. End-diastolic fiber stretch is, in turn, dependent on late diastolic filling due to atrial ejection. This atrial "booster pump" is load-dependent and also responsive to inotropic effect. The interaction of atrial inotropic reserve, LV end-diastolic pressure (atrial afterload) and LV compliance (which mediates LV end-diastolic pressure and volume) may be generically considered as "atrio-ventricular coupling" which, in theory, should be at least partially responsible for modulations in exercise-induced augmentation of cardiac output related to enhancement of LV end-diastolic volume or "preload reserve". Previous studies have suggested that limitations of preload reserve may explain exercise-associated symptoms of congestive heart failure. The potential ability of new technologies to accurately assess atrio-ventricular coupling as it relates to preload reserve present opportunities for investigation into mechanisms of heart failure operative in patients with stiff left ventricles with intact systolic function. Elucidation of these previously unapproachable mechanisms may be important in targeting therapy and the design and analysis of future interventional trials.

In this pilot study, we hypothesize that exercise intolerance in HCM patients is due to limited LV preload-reserve which, in turn, is mediated by disequilibrium of atrio-ventricular coupling and, possibly, limitations in atrial inotropic reserve. We will test novel analytic tools, including measures of LV compliance and load-independent atrial systolic fuction (atrial systolic elastance), in attempts to dissect out the components of atrio-ventricular coupling which underly HCM-associated symptoms and reduced preload reserve. Further, we will assess serum and cardiac MRI markers of myocardial fibrosis to determine the effect of collagen remodeling on LV relaxation, compliance and atrial afterload. Finally, we will examine the effects of short-term cardiac glycoside (inotropic) therapy on atrial systolic elastance, preload reserve and exercise tolerance. The results of this investigation will be implemented in the design of subsequent interventional protocols targeted towards mechanisms of the stiff heart syndrome.
Naproxen sodium tablets are nonsteroidal anti-inflammatory drugs available as follows: Naproxen sodium tablets are available as white tablets containing 275 mg and 500 mg of naproxen sodium for oral administration. Naproxen is a priopionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs. The chemical name for naproxen sodium is (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt. Naproxen sodium has a molecular weight of 252.23 and a molecular formula of C14H13NaO3. Naproxen sodium has the following structure.

Naproxen sodium USP is a white to creamy crystalline powder. It is soluble in water and in methanol, sparingly soluble in alcohol, very slightly soluble in acetone and practically insoluble in chloroform and in toluene.

The inactive ingredients in naproxen sodium tablets include: magnesium stearate, microcrystalline cellulose, povidone and talc. The coating suspension contains hypromellose 2910, polyethylene glycol 400 and titanium dioxide.
Maurocalcine, a novel toxin isolated from the venom of the Tunisian chactidae scorpion  Scorpio maurus palmatus , has the amino acid sequence GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR (SEQ. ID. No. 1). It potently and reversibly modifies channel gating behaviour of type 1 ryanodine receptor (RyR1) by inducing prominent subconductance behavior. Maurocalcine and its bioactive structural analogues—preferably those containing the KKCKRR motif corresponding to part of the II-III loop of the alpha1S subunit of the voltage-dependent skeletal muscle calcium channel dihydropyridine receptor—appear to possess a therapeutic potential, notably as candidate immuno-suppressive drugs, and for the treatment of pathologies in humans that may involve a dysfunction of calcium channels.
Heat stroke induced cerebral damage via neuroinflammation. This study aimed to approach whether heat stress would promote NOD-like receptor protein 3 (NLRP3) inflammasome via reactive oxygen species (ROS). The mice were randomly divided into the sham group, the heat stress group, and the heat stress + TEMPOL (ROS scavenger) group. And the NLRP3 -/- mice were applied and divided into the NLRP3 -/-  + sham group and the NLRP3 -/-  + heat stress group. Furthermore, the BV2 cells were divided into four groups following the intervention measures: the heat stress + TEMPOL group, the heat stress + Z-VAD-FMK (caspase-1 inhibitor) group, the heat stress group, and the control group. ROS levels were examined. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 were detected by western blotting and double immunofluorescence. We found that heat stress attack induced excessive ROS in microglia and subsequently activated NLRP3 inflammasome in both mice and BV2 cells. When ROS scavenged, the expression level of NLRP3 was downregulated. Furthermore, with NLRP3 inflammasome activation, the expression levels of caspase-1, IL-1β, and IL-18 were increased. In NLRP3 -/- mice, however, the caspase-1, IL-1β, and IL-18 were significantly declined. Further experiments showed that pretreatment of caspase-1 inhibitor decreased the expression levels of IL-1β and IL-18. These results suggest that heat stress attack caused neuroinflammation via excessive ROS activating the NLRP3 inflammasome in microglia cells.
The US Food and Drug Administration (FDA)'s authorization of etranacogene dezaparvovec (Hemgenix) is a significant milestone, constituting not only the first FDA approval of a gene therapy for hemophilia but also the first approval of a liver-targeted adeno-associated virus vector gene therapy. This review summarizes the nonclinical studies and clinical development that supported regulatory clearance. Similar to other gene therapies for single gene disorders, both the short-term safety and the phenotypic improvement were unequivocal, justifying the modest-sized safety and efficacy database, which included 57 participants across the phase 2b (3 participants) and phase 3 (54 participants) studies. The most common adverse reactions included liver enzyme elevation, headache, flu-like symptoms, infusion-related reactions, creatine kinase elevation, malaise, and fatigue; these were mostly transient. One participant had hepatocellular carcinoma on a study-mandated liver ultrasound conducted 1 year after vector infusion; molecular analysis of the resected tumor showed no evidence of vector-related insertional mutagenesis as the etiology. A remarkable 96% of participants in the phase 3 trial were able to stop factor IX (FIX) prophylaxis, with the study demonstrating noninferiority to FIX prophylaxis in terms of the primary end point, annualized bleeding rate. Key secondary end points such as the annualized infusion rate, which declined by 97%, and the plasma FIX activity level at 18 months after infusion, with least squares mean increase of 34.3 percentage points compared with baseline, were both clinically and statistically significant. The FDA's landmark approval of Hemgenix as a pioneering treatment for hemophilia stands on the shoulders of >20 years of gene therapy clinical research and heralds a promising future for genomic medicines.
The purpose of this study was to reproduce the previously observed spatial summation of pain effect (SSp) using non-laboratory procedures and commercial equipment. An additional aim was to explore the association between expectations and SSp. The Cold Pressor Task (CPT) was used to induce SSp. Healthy participants (N = 68) immersed their non-dominant hands (divided into 5 segments) into cold water (CPT). Two conditions were used 1) gradual hand immersion (ascending condition) and 2) gradual hand withdrawal (descending condition). Pain intensity was measured on a Visual Analogue Scale (VAS). Psychological factors, such as the participants' expectations of pain intensity were also measured on a VAS. Results showed significant SSp (χ2(4) = 116.90, p < 0.001), reproduced with non-laboratory equipment in a home-based set-up. Furthermore, two novel findings were observed: i) there was a significant correlation between expectations and perceived pain, indicating a link between pain expectations and SSp, ii) spatial summation increased with the increase in duration exposure to the noxious stimulus (Wald χ2(8) = 80.80, p < 0.001). This study suggests that SSp is associated with pain expectations and can be formed by a mixture of excitatory and inhibitory mechanisms potentially driven by temporal characteristics of neural excitation. Moreover, this study proposes a new feasible way to induce SSp using a home-based set-up.
The invention provides rhein-loaded lactoferrin nanoparticles and a preparation method and application thereof, belonging to the technical field of biomedical materials. Specifically provides drug-loaded lactoferrin nanoparticles which are nanoparticles having a three-layer structure; the three-layer structure comprises a pectin layer, a hyaluronic acid layer and a drug-loaded lactoferrin layer from outside to inside. The drug is preferably rhein. The drug-loaded dual-targeting drug delivery nanoparticle has good biocompatibility and stability, can be orally administered, and has good targeting capability. Wherein, the rhein-loaded nano particles have good colon lesion inflammation and colon injury targeting capability. The nano particle can keep stability in stomach and small intestine when being orally taken, releases the medicine slowly, and can release the medicine continuously after targeting to the colon lesion part, thereby having good effect on treating colitis, in particular ulcerative colitis. The nano particles have excellent treatment effect and good application prospect.
PURPOSE: The purpose of this study was to describe the response of a papillomatous ocular surface squamous neoplasia (OSSN) to the intramuscular (IM) 9-valent human papillomavirus (HPV) vaccine after failed medical and surgical interventions.
METHODS: A 79-year-old White man with a conjunctival lesion underwent a biopsy which revealed OSSN and positivity for high-risk HPV. Initially treated with medical therapy and surgical excisions, the patient developed a recurrence and refused further surgery. He was given 4 doses of IM HPV vaccine at the 6-week interval.
RESULTS: A dramatic reduction in lesion size and reduced epithelial thickening and hyperreflectivity was noted on slitlamp examination and high-resolution anterior segment optical coherence tomography after receiving the IM HPV vaccine. Although lesion size was markedly reduced, the therapy did not achieve total resolution, resulting in further treatment with topical 1% 5-fluorouracil (5-FU) eye drops and later 0.04% mitomycin C eye drops. The patient then elected to discontinue further treatment and solely observe.
CONCLUSIONS: This case report adds to the growing literature demonstrating the potential therapeutic use of vaccines in cancer treatment. Although HPV vaccination is currently approved for prophylaxis, the use of HPV vaccines as a therapeutic option for various HPV-mediated diseases, including OSSN, should be further explored. The HPV vaccine yielded significant initial improvement in this patient who refused further surgical interventions. The use of IM HPV vaccine as an adjunctive treatment of papillomatous OSSN may represent a potential therapeutic option in cases refractory to standard treatment modalities.
Participants in the control arm will receive usual care (UC). Sociodemographic, behavioral, and psychosocial data will be collected over a period of 24 months by surveys and from the medical record. To enhance recruitment, those subjects randomized to the usual care control group will be offered to participate in the health coaching arm of the study as well after a period of 6 months. If they refuse, they will continue in the usual care control group.
Galectin 3 will be measured in 30 Patients who are with active stage of pemphigus either newly diagnosed or in a relapse. The diagnosis of each patient is based on clinical examination and histopathological examination.
Continuing advances in computed tomography (CT) in the past decades such as short scanning times with multi-detector CT (MDCT) requires contrast medium (CM) administration to be precisely planned to ensure a diagnostically accurate CT scans. To improve the chest CT diagnostic, the contrast enhancement in the thoracic vessels shoulde be increased.

The most important patient-related factors affecting the magnitude of vascular and parenchymal contrast enhancement are body weight. Historical practice has been to use a fixed volume of CM independent of body weight. Research has shown a clear relationship between vessel enhancement and patient weight, and that fixed CM volume technique is inappropriate, as smaller patients may receive excessive volume, and larger patients insufficient volume resulting in reduced image quality and poor diagnostic. In addition, excess CM can result in contrast induced adverse effects and nephropathy. To overcome these problems, it is essential to adjust the CM volume to the patient's total body weight and body composition. This adjustment can be done in different ways. The aim of this study is to identify which weight/body tailored CM administration is the best replacement for fixed CM administration in chest CT. The cost and procedure time will also be explored.
During the early recovery period after traumatic brain injury (TBI), referred to as post-traumatic amnesia (PTA), approximately 44% of individuals may exhibit agitated behaviours. Agitation can impede recovery and poses a significant management challenge for healthcare services. As families provide significant support for their injured relatives during this time, this study aimed to explore the family's experience during PTA to better understand their role in agitation management. There were 20 qualitative semi-structured interviews conducted with 24 family members of patients exhibiting agitation during early TBI recovery (75% female, aged 30-71 years), predominantly parents (n = 12), spouses (n = 7) and children (n = 3). The interviews explored the family's experience of supporting their relative exhibiting agitation during PTA. The interviews were analyzed using reflexive thematic analysis, which revealed three key themes: family contributions to patient care, expectations of the health care service and supporting families to support patients. This study emphasized the significant role of families in managing agitation during early TBI recovery and highlighted that families who are well-informed and well-supported have the potential to minimize their relative's agitation during PTA, which may reduce the burden on healthcare staff and promote patient recovery.
Participants completed a control condition on a separate day. This condition followed the same sequence of events as the stress condition with the exception that the 20-minute TSST was replaced with a 20-minute low-affect educational film screening.
The patients receive 0.5mg/kg ICG intravenous injection before surgery. The search for lumbar nerve roots is performed with the assistance of fluoroscopic endoscopic imaging equipment. And the procedure follows standard endoscopic spinal surgery procedures.
A randomized, controlled, cross-over study designed to examine the postprandial glycaemic response and appetite related sensations to peas in muffins will be conducted at the I.H. Asper Clinical Research Institute in Winnipeg, Manitoba. Eligible participants who have provided consent will be asked to attend 4 clinic visits in a fasted state. Participants will be given muffins containing peas at 2 visits and muffins without peas at 2 visits. At each visit participants will provide 7 venous blood samples via indwelling catheter, 7 capillary blood samples via finger poke, 2 urine samples, 5 questionnaires about their appetite and a questionnaire about the acceptability of the products. At the end of each visit, participants will eat pizza ad libitum, and the amount of pizza consumed will be measured to determine if the peas influenced the amount of calories consumed at lunch. Participants will record their food/beverage intake for the rest of the day. Each visit will last approximately 3h and be separated by 3-14 days.
Corticosteroids, including deflazacort oral suspension, can cause elevation of blood pressure, salt, and water retention, and increased excretion of potassium and calcium. Monitor blood pressure and assess for signs and symptoms of volume overload. Monitor serum potassium levels.

Dietary salt restriction and potassium supplementation may be necessary. Deflazacort oral suspension should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.

Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with deflazacort oral suspension should be used with great caution in these patients.
Medicontur Bi-Flex 677MY IOL was implanted into 24 eyes of 12 patients during cataract surgery. Angle kappa, biometric data and IOL decantation were measured.
Infectious diseases lead to significant morbidity and mortality. Often, resolution of the acute stage of the disease leads to microbial persistence, resulting in chronic debilitating disease. Management of persistent infections frequently requires lifelong therapy with antimicrobial agents. These infections could be chronic viral infections like HIV, hepatitis B or chronic bacterial persistent infections like prosthetic joint infections caused by multi-drug resistant organisms. Bacteriophages have been designed specifically to target recalcitrant bacterial infections, such as prosthetic joint infections with varying success. In this review, we describe the historic evolution of scenarios and risks associated with innovative therapy using infectious agents to treat other persistent infections.