anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In the bone marrow, a reservoir of EPCs does exist, which can be mobilized into circulation when needed, for example during ischemia, a situation which may occur in sickle cells disease. These cells are able to reach distant targets and to participate to the neovascularisation processes necessary for tissue and vascular healing. Conversely, abnormalities of the maturation, mobilization or homing processes would contribute to the thrombotic and ischemic risks associated to ischemia. Furthermore, vascular stress such that encountered in SCD leads to the detachment of endothelial cells from the vessels. The number of detached mature circulating endothelial cells (CEC) seems to be related to vascular hurting. The balance between EPCs and CECs would thus be informative of the vascular condition in patients during the progression of the disease. A relatively high level of EPCs would indicate a prominence of a healing neoangiogenesis or vasculogenesis process, while increasing levels of CECs would be indicative severe progression of the disease. Our studies and those published by others indicate that the number of EPCs in peripheral blood is tightly regulated. Indeed, mediators of inflammation could participate to EPC mobilization and to their recruitment to the diseased areas by local activation of the vascular endothelium. In this context, sickle cells disease provokes transient occlusion episodes, leading to a situation of chronic ischemia in different organs, sometimes with acute episodes. This suggests defect of the maintenance of the vascular integrity in these target organs.Within this project, we will compare the number of EPCs and CECs in 25 SCD patients and 25 normal individuals in search of a correlation with the severity of the disease. SCD patients with potential confounding factors that may alter endothelial physiology (drugs, blood transfusions, hydroxyurea therapy) are excluded. In addition, we will analyse and compare in culture and in vivo the phenotypic and functional characteristics of EPCs obtained from patients and controls. We have a working bilateral hypothesis, since we do not know whether SCD subjects have appropriate angiogenic balance (high EPCs/CEC ratio with functional EPCs) to face the situation of endothelial activation and tissue hypoxia induced by SCD. Therefore, we will quantitatively and qualitatively study several distinct biological steps:1. Evaluate the number of colonies generated by the EPCs in culture and their kinetics of appearance in patients (major end point)2. Enumerate EPCs and CECs by flow cytometry using a specific set of markers (CD133, CD146, KDR).3. Measure of the plasma concentrations of PlGF, VEGF, EPO, ET-1, modulators of angiogenesis.4. Test of correlations between these respective characteristics of EPCs with clinical vascular abnormalities of the disease (retinopathy assessed by angiography, nephropathy, leg ulcers) and severity of vaso-occlusive crisis assessed by number and length of hospitalizations during the previous year and during the study.
PURPOSE:A tooth paste composition that contains a specific vanillyl alcohol derivative with a strong pungent taste, thus increasing refresh feeling to make the oral cavity feel refreshed. CONSTITUTION:One or more vanillyl alcohol derivatives of the formula (R is 1-6C alkyl) are added to the tooth paste materials. The amount of the alcohol derivative is 2-15ppm based on the composition. The compound of the formula is practically produced by heating the alkyl ether together with hydrochloric acid by about 5wt% based on the corresponding alkyl alcohol to about 70 deg.C, then gradually adding vanillyl alcohol and effecting through reaction at 70 deg.C. An example of the compound of the formula is vanillyl methyl ether or vanillyl n- butyl ether. EFFECT:The compound makes it possible to put less amount of menthol to use.
Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.
There is disclosed a training system for training people, for example to increase their ice skating skills or some other physical attribute. In a preferred embodiment, the training system comprises a computer and a database. The training system allows a user to enter information regarding his fitness. The system can then specify an exercise program for the user. The user can also enter information regarding his diet, in which case the system determines the suitability of the diet to the user. In order to psychologically motivate the user, the system provides a goal orientated method to facilitate the user to understand ways in which he can improve his performance. The system can also receive information regarding injuries and can take these into account when generating a training program and when assessing the user's diet. The system can also be used for the purpose of weight loss or gain.
Chronic schizophrenia is a longer-term condition that is characterized by a lack of drive, underactivity and slowness, and social withdrawal. As with the acute form of schizophrenia, delusions and hallucinations are common. This is a randomized, double-blind, parallel-group study to evaluate the effectiveness and safety of five dosages of risperidone (1, 4, 8, 12, or 16 mg per day) compared with a fixed dose of a standard antipsychotic, haloperidol (10 mg per day) in patients with chronic schizophrenia. The study is composed of two phases: a 1-week period, in which patients receive placebo and all current medication for schizophrenia treatment is stopped, and a double-blind treatment phase. The doses of study drug are increased progressively during the first week of the double blind period and then remain constant for the next 7 weeks. The primary measures of effectiveness are the percent of patients showing clinical improvement on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the average total PANSS score, from baseline to the end of double-blind treatment. The PANSS is a rating scale that measures the symptoms of schizophrenia. Safety evaluations include the incidence of adverse events, results of clinical laboratory tests (hematology, biochemistry, urinalysis, and hormone levels), plasma levels of risperidone, measurements of vital signs and body weight, physical examination and electrocardiogram (ECG) findings, neurological examinations, and the Extrapyramidal Symptoms Rating Scale (ESRS), a scale used to measure effects of antipsychotic medications on motor functions of the patient. The study hypothesis is that risperidone doses of 4, 8, 12, or 16 mg/day are more effective than risperidone 10 mg/day, as measured by clinical improvement on PANSS and the average total score for PANSS, in patients with chronic schizophrenia. Risperidone oral tablets, twice-daily, starting with 1 or 2 mg/day, increasing gradually in Week 1 (except for 1 mg/day group), then 0.5, 2, 4, 6, or 8 mg twice daily for 7 weeks. Haloperidol oral tablets, twice-daily, starting with 2 mg/day, increasing to 5 mg twice daily in Week 1, then 5 mg twice daily for 7 weeks.
PURPOSE:Animal blood is subjected to a variety of purification processes to produce the titled solution of high stability with time and with ease. CONSTITUTION:Fibrin is formed in animal blood such as of calf or cattle and separated. The remaining product is subjected to dialysis to remove protein. The dialysis is effected by placing the substrate to be deproteinized in a semipermeable membrane such as a bladder membrane and dipping them in water. Then, the dialyzed blood is concentrated to 1/5 volume of the original. Then, the concentrate is adjusted in pH to 9.5-11.5 and the precipitate formed is removed by filtration. Then, the pH is adjusted to lower than 5 to degass the solution. Further, the solution is brought into contact with an ion-exchange substance at any stage after the fibrin removal to control the potassium ion concentration to less than 300mg/dl in the blood extraction solution to give the objective product. The product is effective for treating a variety of diseases.
The invention relates to a formula and a production technique of an externally applied plaster for treating herpes zoster. The invention is characterized in that the externally applied plaster is prepared from rhubarb, radix trichosanthis, pearl powder, coptis, phellodendron bark, cotton rose hibiscus leaf, boneset leaf, bulbus fritillariae cirrhosae, paenoia albiflora, licorice root, frankincense, myrrh, bezoar, borneol, realgar, purslane, impatiens balsamina and vaseline. The drugs are combined to produce synergetic effect. When being applied to the affected part once or twice a day, the externally applied plaster can quickly relieve heat, promote the subsidence of swelling, alleviate pain, remove heat from the blood, promote the blood circulation, accumulate heat and remove toxicity, and the affected part can heal after 5-10 days. The invention has the advantages of easily available raw materials, simple technique, less pain and high safety and reliability, and is convenient in operation; and the effective rate is 100%, and the cure rate is 5%. The externally applied plaster has excellent market prospects and high development value, and is worthy of popularization.
Balancing selection is an evolutionary process that maintains genetic polymorphisms at selected loci and strongly reduces the likelihood of allele fixation. When allelic polymorphisms that predate speciation events are maintained independently in the resulting lineages, a pattern of trans-species polymorphisms may occur. Trans-species polymorphisms have been identified for loci related to mating systems and the MHC, but they are generally rare. Trans-species polymorphisms in disease loci are believed to be a consequence of long-term host-parasite coevolution by balancing selection, the so-called Red Queen dynamics. Here we scan the genomes of three crustaceans with a divergence of over 15 million years and identify 11 genes containing identical-by-descent trans-species polymorphisms with the same polymorphisms in all three species. Four of these genes display molecular footprints of balancing selection and have a function related to immunity. Three of them are located in or close to loci involved in resistance to a virulent bacterial pathogen, Pasteuria, with which the Daphnia host is known to coevolve. This provides rare evidence of trans-species polymorphisms for loci known to be functionally relevant in interactions with a widespread and highly specific parasite. These findings support the theory that specific antagonistic coevolution is able to maintain genetic diversity over millions of years.
This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level.
In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection.
BACKGROUND: To compare the performance between one-slice two-dimensional (2D) and whole-volume three-dimensional (3D) computed tomography (CT)-based radiomics models in the prediction of lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC).
METHODS: Two hundred twenty-four patients with ESCC (158 LVI-absent and 66 LVI-present) were enrolled in this retrospective study. The enrolled patients were randomly split into the training and testing sets with a 7:3 ratio. The 2D and 3D radiomics features were derived from the primary tumors' 2D and 3D regions of interest (ROIs) using 1.0 mm thickness contrast-enhanced CT (CECT) images. The 2D and 3D radiomics features were screened using inter-/intra-class correlation coefficient (ICC) analysis, Wilcoxon rank-sum test, Spearman correlation test, and the least absolute shrinkage and selection operator, and the radiomics models were built by multivariate logistic stepwise regression. The performance of 2D and 3D radiomics models was assessed by the area under the receiver operating characteristic (ROC) curve. The actual clinical utility of the 2D and 3D radiomics models was evaluated by decision curve analysis (DCA).
RESULTS: There were 753 radiomics features from 2D ROIs and 1130 radiomics features from 3D ROIs, and finally, 7 features were retained to construct 2D and 3D radiomics models, respectively. ROC analysis revealed that in both the training and testing sets, the 3D radiomics model exhibited higher AUC values than the 2D radiomics model (0.930 versus 0.852 and 0.897 versus 0.851, respectively). The 3D radiomics model showed higher accuracy than the 2D radiomics model in the training and testing sets (0.899 versus 0.728 and 0.788 versus 0.758, respectively). In addition, the 3D radiomics model has higher specificity and positive predictive value, while the 2D radiomics model has higher sensitivity and negative predictive value. The DCA indicated that the 3D radiomics model provided higher actual clinical utility regarding overall net benefit than the 2D radiomics model.
CONCLUSIONS: Both 2D and 3D radiomics features can be employed as potential biomarkers to predict the LVI in ESCC. The performance of the 3D radiomics model is better than that of the 2D radiomics model for the prediction of the LVI in ESCC.
Our recently published studies in children with septic shock demonstrated that pediatric septic shock is characterized by large scale repression of genes that either directly depend on normal zinc homeostasis or directly participate in zinc homeostasis. Functional validation studies demonstrated that nonsurvivors of pediatric septic shock have abnormally low serum zinc concentrations. A follow-up pilot study in a general population of critically ill children demonstrated that the presence of low plasma zinc concentrations is a prevalent problem in critically ill children. In addition, low plasma zinc concentrations correlate inversely with indices of inflammation and directly with the number of organ failures. These preliminary data, coupled with the expected safety of zinc supplementation, provided the rationale for a double blinded, prospective, placebo-controlled trial of zinc supplementation in critically ill children, with the two primary study endpoints to assess efficacy being highly clinically relevant: reduction of the lymphopenia rate and improvement of glucose homeostasis. Although the proposal was well-received, the primary concern precluding funding of this trial were lack of safety and dosing data for intravenous zinc. We have therefore developed a proposal for a Phase I/II study of safety and pharmacokinetics to address these concerns. It is anticipated that data generated through this proposal will provide the necessary preliminary data to re-submit our application for an interventional efficacy trial of zinc supplementation in critically ill children
BACKGROUND: Functional dyspepsia is a common functional gastrointestinal disorder that is often challenging to treat. Psychotherapeutic interventions have been proposed as an alternative or adjunctive approach to conventional treatments, but their efficacy remains unclear.
OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy of psychotherapeutic interventions in the treatment of functional dyspepsia.
METHODS: A comprehensive search of electronic databases was conducted, from inception to March 2023, for randomized controlled trials (RCTs) that evaluated the effects of psychotherapeutic interventions on patients with functional dyspepsia. The primary outcome measures were gastrointestinal symptoms, quality of life, depression, and anxiety. Data were extracted and analyzed using Review Manager 5.3 software. The risk of bias of the included studies was assessed using the Cochrane Risk of Bias tool.
RESULTS: Sixteen RCTs comprising 1550 patients with functional dyspepsia were included in the meta-analysis. The types of psychotherapeutic interventions used in the included studies were cognitive-behavioral therapy (CBT), hypnotherapy, and mindfulness-based stress reduction (MBSR). The control groups were usual care, placebo, supportive therapy, or no treatment. The meta-analysis showed that psychotherapeutic interventions had a significant effect on reducing gastrointestinal symptoms,depression and anxiety in patients with functional dyspepsia. However, no significant improvement was observed in the quality-of-life scores of patients who received psychotherapeutic interventions compared to those in the control group.
CONCLUSION: Psychotherapeutic interventions, such as CBT, hypnotherapy, and MBSR, could be a useful adjunct to conventional treatments for functional dyspepsia, as they were found to significantly reduce gastrointestinal symptoms and anxiety in patients. However, further studies are needed to assess the long-term effects and generalizability of these interventions.
BACKGROUND: Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored.
METHODS: To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1).
RESULTS: In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy.
CONCLUSIONS: Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.
OBJECTIVE: Currently, there is little information about the risk of sudden cardiac death and its predictors in aortic valve stenosis patients after transcatheter aortic valve replacement (TAVR). Therefore, we conducted a large sample cohort study on TAVR patients to evaluate the predictive factors and incidence of heart failure death caused by advanced heart failure (AHF) and sudden cardiac death. Furthermore, a nomogram model to predict its risk was constructed.
METHODS: This study retrospectively analyzed the data of 241 consecutive participants who had received TAVR treatment for aortic valve stenosis in our hospital from January 2020 to January 2022. The characteristics of the subjects, including myocardial zymogram, renal function, biochemical parameters, and cardiac ultrasound parameters, were collected. Moreover, a nomogram was constructed to predict the risk of sudden cardiac death and its predictors in patients after transcatheter aortic valve replacement (TAVR). The model was validatedinternally using measures of calibration and decision curve analysis.
RESULTS: Six independent risk factors(Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose) were finally recruited into the nomogram model to predict the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. Besides, the decision curve analysis and receiver operating characteristic curve indicated that the nomogram prediction models showed positive clinical benefits.
CONCLUSIONS: The Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose are the independent risk factors for advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. The construction of nomograms is beneficial in predicting the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR.
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that are RB1 intact with a local grade 1-2 estrogne receptor positive (ER+) are assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Subjects in Group B will be randomized to receive levocetirizine ODT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 2.