anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Marrow adipocytes have been identified as a component of the bone marrow micro-environment. Evidence exists suggesting that marrow fat plays an important physiologic role in both bone mineral and energy metabolism in humans. Studies have shown that nutritional status, particularly body fat distribution, may be important in marrow fat. For example, anorexia nervosa, a state of low body fat, is associated with elevated marrow adiposity and low bone mineral density. However, it is not known whether this is in direct response to nutritional deprivation or other hormonal changes that occur in anorexia nervosa. Drugs known to cause adipose redistribution and associated with low bone mass, such as the thiazolidinediones and glucocorticoids, have also been shown to stimulate the accumulation of marrow adipocytes. Therefore, the relationship between bone marrow fat, bone mass, body fat depots and their hormone regulators is a dynamic one and not yet well understood. Although studies have shown an inverse relationship between high marrow adiposity and low bone mineral density (BMD), the physiologic role of marrow adipose tissue has not been defined nor its relationship to hormonal factors in humans. A role for marrow adipose tissue (MAT) in mineral and energy metabolism is further supported by the fact that a number of pathologic states are associated with increased marrow adiposity. Visceral adipose tissue, intramyocellular lipids (IMCL), intrahepatic lipids (IHL) and serum triglycerides, all of which are elevated in obesity, are also positive predictors of MAT, but whether acute weight gain in humans results in elevated marrow adiposity is unknown. Therefore observing changes in marrow fat during acute weight gain and acute nutritional deprivation will further the understanding of the role of marrow adiposity in energy homeostasis. While it is known that markers of bone formation dramatically decrease after only 4 days of fasting, it is not known how quickly marrow fat can change in response to physiologic cues. In a rat model, increases in marrow fat were observed after 14 days in space suggesting that changes in marrow adiposity may occur acutely in the human model as well.
Cardioplegias are routinely used in cardiac surgery to protect the heart from ischemia. Choice of the cardioplegia depends on surgeons clinical experience and preference. Various cardioplegia solutions (such as Bretschneider, del Nido, blood cardioplegia, crystalloid cardioplegia, St. Thomas) are widely used in clinical practice. There is no clear scientific data in the current literature that demonstrates the superiority of one cardioplegia over the others.

In this study preferred the blood and del Nido cardioplegia solutions, which are commonly used in clinic. Blood cardioplegia is an autologous cardioplegia that includes physiological buffer systems, allowing for heart nourishment and containing native antioxidant systems. However, the need for repeated doses every 20 minutes after the initial application creates a disadvantage in terms of surgical comfort. On the other hand, del Nido cardioplegia is preferred by surgeons in complex cases due to its long application intervals.

The adequacy of a single dose for up to 90 minutes after the initial application creates an advantage in terms of surgical comfort and surgical integrity. However, the content being predominantly electrolyte-based, containing 1:4 ratio of autologous blood, and the extended time of a single dose are disadvantages compared to blood cardioplegia in terms of heart nourishment and protection from ischemia. Hamad et al reported that del Nido and blood cardioplegia solutions offer equivalent safety in combined adult valve surgery. In addition to these differences, the myocardial protective effects of cardioplegias on myocardial redox homeostasis are also among the current research topics. Ischemia and reperfusion injury can be observed in the myocardial tissues of patients undergoing coronary artery bypass graft surgery and isolated valve replacement surgery. It was reported that coronary sinus blood sampling gives an insight into the localized pathophysiology of heart diseases. Comparative research examining the effects of blood and del Nido cardioplegia solutions on coronary sinus redox status is not currently available in the literature. The study aim to contribute to the development of effective strategies to minimize oxidative damage associated with cardiac surgery by investigating the effects of blood and del Nido cardioplegia solutions on coronary sinus redox homeostasis during the preoperative and postoperative periods using redox biomarkers and antioxidant system transcription factors. Thesis project also intend to compare these redox effects with elective isolated valve replacement surgery patients, who do not have coronary artery disease but share a similar pathogenesis with potential strategies for minimizing oxidative damage associated with cardiac surgery using cardiopulmonary bypass (CPB).
The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Muscle rigidity sometimes accompanied by hyperthermia has been reported following use of fluphenazine decanoate. Most often these extrapyramidal symptoms are reversible, however, they may be persistent (see below). The frequency of such reactions is related in part to chemical structure: one can expect a higher incidence with fluphenazine decanoate than with less potent piperazine derivatives or with straight-chain phenothiazines such as chlorpromazine. With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.

Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as Benztropine Mesylate or intravenous Caffeine and Sodium Benzoate Injection, and by subsequent reduction in dosage.

###  Dystonia:

Class effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy.
Patients will undergo no therapeutic intervention outside of steroid injection. If they are in the inflammatory phase of the condition, they will receive 40 mg of depot methylprednisolone in solution with 2 cc of 1% lidocaine.
Nisin-subtilin mutant and chimeric pre-peptides were constructed and expressed in a Bacillus subtilis strain that possesses all of the cellular machinery for making subtilin, except for the pre-subtilin gene. The chimera S L  -Nis 1-11  -Sub 12-32  was prepared. This pre-peptide has the subtilin leader sequence (S L ), the N-terminal portion of the structural region derived from nisin and the C-terminal portion of the structural region derived from subtilin. This chimera was accurately and efficiently converted to the mature lantibiotic, as demonstrated by a variety of physical and biological activity assays. In contrast, a S L  -Sub 1-11  -Nis 12-34  chimera was processed into a heterogeneous mixture of products, none of which appeared to be the correct chimeric lantibiotic. The mixture did, however, contain an active minor component with a biological activity that exceeded nisin itself.
There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and -25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. STATEMENT OF SIGNIFICANCE: Bacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments.
Childhood obesity has more than doubled in children and tripled in adolescents in the past 30 y. As consequence, increasingly children and adolescents suffer from elevated blood pressure, impaired glucose tolerance, hyperinsulinemia, dyslipidemia. Obesity has a multifactorial etiology since there are potentially numerous contributors to its development and progression. Chronobiology, the science that studies periodic (cyclic) changes in living organisms, has been recently proposed as a new and promising topic to investigate. Alterations of circadian (24 h oscillations) system may contribute to obesity and its complications development such as high blood pressure, insulin resistance, altered fasting lipid profile. Conversely, in a vicious manner, obesity has been regarded as a fault in the circadian system explainable by the association with imbalances and fluctuations of hormones/genes expressions rhythms under the influence of body weight changes.

Thus, the study will examine changes in circadian rhythmicity over a week period. The primary end point will be to evaluate differences between obese/overweight and non-obese children in chronotypes and the responses of these parameters to meal patterns. In particular, non-invasive measures that are well-established determinants of chronotypes will form the core endpoints for the study. Well designed and age-appropriate questionnaires will provide further information in order to study correlations with eating, sleeping and sedentary/active behaviors.
Active Brownian disks moving in two dimensions that exchange information about their internal state stochastically are chosen to model epidemic spread in a self-propelled population of agents under the susceptible-infected-recovered-susceptible (SIRS) framework. The state of infection of an agent, or disk, governs its self-propulsion speed; consequently, the activity of the agents in the system varies in time. Two different protocols (one-to-one and one-to-many) are considered for the transmission of disease from the infected to susceptible populations. The effectiveness of the two protocols are practically identical at high values of the infection transmission rate. The one-to-many protocol, however, outperforms the one-to-one protocol at lower values of the infection transmission rate. Salient features of the macroscopic SIRS model are revisited, and compared to predictions from the agent-based model. Lastly, the motility induced phase separation in a population of such agents with a fluctuating fraction of active disks is found to be well-described by theories governing phase separation in a mixture of active and passive particles with a constant fraction of passive disks.
Granulocyte-colony stimulating factor (G-CSF) is konwn to have no significant effect on leukemia stem cells and has been widely used in the patients with agranulocytosis after chemotherapy. Minimal residual disease (MRD), an good index for early treatment response, plays an important role in prognostic prediction. Numbers of data have shown MRD at day 14 after induction therapy significantly predicts prognosis. However, the retrospetive data from the investigators showed that patients with G-CSF treatment after induction had higher MRD at day 14 but not significantly different at day 28,suggesting that G-CSF might work on the differenciation of hemapoetic stem cells and increase MRD level at day 14. In this multicenter prospective study, the investigators randomizedly divide all participants with newly diagnosed acute myeloid leukemia (AML) into G-CSF treatment group and G-SCF-free group. In G-CSF treatment group, all participants are treated with G-CSF at the dose of 5ug/kg pre day until neutrophil higher than 0.5 g/L or 14 days from day three after induction therapy. MRD is monitored at day 14 and 28 with flow cytometry and quantity PCR if a fusion gene is available in both G-CSF treatment and G-CSF-free groups. Comparision of the difference of MRD levels between the two groups is performed to evaluate the effect of G-CSF on MRD.
Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the management of relapsed and/or refractory multiple myeloma (RRMM). However, CAR-T treatment failure is not uncommon and remains a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures in patients with RRMM. The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between September 2023 and December 2023 to determine myeloma, transplantation, and cellular therapy physicians' practice patterns for the surveillance, diagnosis, and management of CAR-T failure. The intent of this survey was to understand clinical practice patterns and identify areas for further investigation. Email surveys were sent to 1311 ASTCT physician members, of whom 80 (6.1%) completed the survey. The respondents were 58% white and 66% male, and 51% had >10 years of clinical experience. Most (89%) respondents were affiliated with a university/teaching center, and 56% had a myeloma-focused transplantation and/or cellular therapy practice. Post-CAR-T surveillance laboratory studies were commonly done every 4 weeks, and surveillance bone marrow biopsies and/or imaging surveillance were most commonly done at 3 months. Sixty-four percent of the respondents would often or always consider biopsy or imaging to confirm relapse. The most popular post-CAR-T failure rescue regimen was GPRC5D-directed immunotherapy (30%) for relapses occurring ≤3 months and BCMA-directed bispecific therapies (32.5%) for relapse at >3 months. Forty-one percent of the respondents endorsed post-CAR-T prolonged cytopenia as being "often" or "always" a barrier to next-line therapy; 53% had offered stem cell boost as a mitigation approach. Substantial across-center variation in practice patterns raises the need for collaborative studies and expert clinical recommendations to describe best practices for post-CAR-T disease surveillance, optimal workup for treatment failure, and choice of rescue therapies.
Disclosed are novel polymers derivatized with at least one -SNO group per 1200 atomic mass unit of the polymer. In one embodiment, the S-nitrosylated polymer has stabilized -S-nitrosyl groups. In another embodiment the S-nitrosylated polymer prepared by polymerizing a compound represented by structural formula (1). R is an organic radical. Each X' is an independently chosen aliphatic group or substituted aliphatic group. Preferably, each X' is the same and is a C2-C6 alkylene group, more preferably -CH2-, -CH2CH2-, -CH2CH2CH2- or -CH2CH2CH2CH2-. pand m are independently a positive integer such that p + m is greater than two. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.
Sepsis is a severe inflammatory syndrome with high mortality and morbidity. Sepsis-induced myocardial dysfunction (SIMD) is a common cause of death in sepsis. The female sex is less susceptible to sepsis-related organ dysfunction, although the underlying mechanism of this sex difference remains unclear. This study explored the role of estrogen receptor G protein-coupled estrogen receptor 30 (GPR30) in septic cardiac dysfunction. Results from the present study indicated that GPR30 activation by the G1 agonist protected female mouse hearts against SIMD exposed to lipopolysaccharides. However, this beneficial effect was absent in female ACE2-knockout mice, as demonstrated by poorer cardiac contractility, myocardial injury, and necroptosis. We also demonstrated that the Stat6 transcription factor induced ace2 transcription by enhancing its promoter activity under GPR30 activation in septic hearts. The adenovirus-mediated inhibition of ACE2 targeting c-FOS expression reversed the deterioration, restored cardiac function, and improved survival in female ACE2-knockout mice. These results demonstrate the essential role of GPR30/STAT6/ACE2/c-FOS-mediated necroptosis in G1-mediated protection and provide novel insight into the pathogenesis of sepsis-related organ damage.
Monitoring nociception accurately during general anaesthesia has presented a long-standing difficulty. Typically, anaesthesiologists rely on changes in the autonomic nervous system, such as heart rate, blood pressure, and sweating, to help determine the need for pain relief medication. Analgesia nociception index (ANI) is a noninvasive tool for monitoring the intraoperative state of the autonomic nervous system, particularly the parasympathetic nervous system.

During the long-lasting high nociceptive surgery, the infusion of fentanyl was used at our institution. Opioids can lead to postoperative nausea, vomiting, and other complications when an overdose occurs. Fentanyl dosage changes significantly after hours of infusion due to context-sensitive halftime. It is practically impossible to adjust an infusion dose with the subjective evaluation of standard monitoring, such as heart rate and blood pressure. Doses of opioids that we use in our daily practice, e.g. mcg.kg-1, are unpredictable and vary between individuals due to pharmacogenetics and pharmacokinetic reasons. The best method to exclude pharmacokinetic peculiarities and predict the subsequent dose is to directly measure analgesic agents' concentration in the blood, though it is practically impossible. This study aimed to assess whether intraoperative analgesia nociception monitoring (ANI) could have an impact on the average intraoperative dose of fentanyl and on the occurrence of postoperative nausea and vomiting.
The present invention relates to a pharmaceutical dosage form for transmucosal delivery of an active agent to two or more mucosal surfaces. The dosage form is presented as a transmucosal delivery device. The devices of the invention may include at least two mucoadhesive surfaces. The devices may further include an intermediate layer disposed between the mucoadhesive layers. The pharmaceutical can be incorporated in any one or all of the mucoadhesive layers or the intermediate layer. Upon application, the device adheres to at least two surfaces, providing transmucosal delivery of the drug to at least two surfaces.
The disclosure relates to compositions comprising PU.1 inhibitors as well as methods of making and using the same. In some embodiments, methods of screening compounds for PU.1 inhibition are disclosed. In some embodiments, methods of screening a plurality of compounds for PU.1 inhibition are disclosed. In some embodiments, lambda-beta binding (LBB) motifs are used to screen compounds for PU.1 inhibition. In some embodiments, methods of treating neurodegenerative disorders are disclosed. In some embodiments pharmaceutical compounds are provided. In some embodiments, methods of treating Alzheimer's disease, inflammation, or excessive myelin uptake with PU.1 inhibitors are disclosed.
Donepezil 5 mg capsules daily for 14 days. Donepezil 10 mg capsules daily for 56 days.
PURPOSE: To obtain the subject suppressing agent composed of 2"-O- glycosylisovitexin as effective component having suppressive activity against brain nerve cell injury attributable to active oxygen atom and useful for treating ischemic cerebropathy, etc. CONSTITUTION: This is the objective suppressive agent composed of 2"-O- glycosylisovitexin as effective component. 2"-O-Glycosylisovitexin is obtained e.g. by extracting and separating it from young green barley leaves as an anti- oxidant active substance. Further, the suppressive agent is obtained e.g. by homogeneously mixing 2"-O-glycosylisovitexin, milk sugar, crystal cellulose, talc and CMC of a binding agent, granulating the mixture and pressing the granules to a tablet after adding magnesium stearate. The dose of the suppressive agent is preferably 0.2-50mg/kg-body weight/day in terms of the active component.