anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Patients who consent to participate in the study will be evaluated for eligibility according to their medical history, physical examination, blood testing, and computed tomography (CT) scan of thorax, abdomen, and pelvis. Those patients who qualify for the study will receive up to 4 intravenous doses of CRS-207, 21 days apart. After each infusion, they will be monitored overnight in an in-patient facility, including collection of blood specimens. Study participants will return after each infusion for outpatient follow-up visits for further blood tests and additional monitoring of safety and immune response to CRS-207. Participants will have repeat CT scans to measure tumor size after the 2nd dose and again after the 4th dose. On Day 91 participants will be discharged from the study. All study participants will be eligible to participate in a long-term follow-up study with a visit 6 months after the final dose of CRS-207 and annually thereafter for evaluation of disease progression, survival, and potential long-term toxicity of CRS 207.
The mono- or multi-vesicular structure useful as transport delivery system for hydrophilic and/or hydrophobic compound and useful in food, cosmetics or pharmaceutical products, comprises a 70-89 mass% of hydrophobic phase (2), an emulsifying agent (3.5 mass%), and a stabilizer (0.8 mass%). The structure is delimited by a 0-22.5 mass% of lipidic bilayer (3) formed by amphiphilic lipids (13-16 mass%), where the bilayer contains a hydrophilic phase (3.8-8.5 mass%). The amphiphilic lipids of the lipidic bilayer have their hydrophilic part directed inwards to the bilayer. The mono- or multi-vesicular structure useful as transport delivery system for hydrophilic and/or hydrophobic compound and useful in food, cosmetics or pharmaceutical products, comprises a 70-89 mass% of hydrophobic phase (2), an emulsifying agent (3.5 mass%), and a stabilizer (0.8 mass%). The structure is delimited by a 0-22.5 mass% of lipidic bilayer (3) formed by amphiphilic lipids (13-16 mass%), where the bilayer contains a hydrophilic phase (3.8-8.5 mass%). The amphiphilic lipids of the lipidic bilayer have their hydrophilic part directed inwards to the bilayer and hydrophobic part directed outwards to the bilayer. The structure is formed by a large vesicle (1) comprising vesicles of smaller size in its hydrophobic phase. The vesicles of smaller size comprised in the large vesicle are juxtaposed and concentric. The emulsifying agent and the stabilizer are added to the amphiphilic lipids of lipidic bilayers. The hydrophilic phase contained in the lipidic bilayers is constituted of water (4 mass%). The hydrophilic phase comprises an agent acting as oxygen barrier (0.11 mass%), an agent capable of increasing a rigidity of the lipidic bilayer and/or decreasing availability of hydrophilic phase, and a hydrophilic compound. The hydrophilic compound comprises active substances, hydrophilic pharmaceutical and/or cosmetic ingredients or hydrophilic food ingredients. The hydrophobic phase is constituted of a neutral hydrophobic compound and/or a hydrophobic compound (75 mass%). The hydrophobic compound comprises active substances, hydrophobic pharmaceutical and/or cosmetic ingredients or hydrophobic food ingredients, and an antioxidant (3.5 mass%). The agent capable of increasing the rigidity of the lipidic bilayer and/or decreasing the availability of hydrophilic phase represents 0.705 mass% with respect to a total mass of the structure. Independent claims are included for: (1) a fatty phase of a product; (2) a food product; and (3) a process of preparing mono- or multi-vesicular structure.
BACKGROUND: Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients.
METHODS: Three hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing.
RESULTS: The frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR.
CONCLUSION: The samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.
BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear.
METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays.
RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPβ phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo.
CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.
Ialuril therapy for 6 months followed by nitrofuranoïne (or trimethoprim) prophylactic therapy for 6 months. In between therapies there is a 4 week wash-out period.
A stable acidic preparation for application to the human skin, e.g. an oil-in-water emulsion, comprises a lipophilic phase and an aqueous hydrophilic phase which is at a pH between 3 and 7 and contains gluconic acid and a water-soluble inorganic gluconate together amounting to less than about 10% by weight of the preparation.  In preparing the compositions, glucono-delta-lactone may be employed which hydrolyzes in aqueous solution to give an equilibrium mixture of the free acid and the delta- and gamma-lactones.  The gluconate may be added as such or may be formed in situ from the acid by addition of a suitable basic material, e.g. sodium hydroxide, carbonate or bicarbonate. Optional ingredients which may be present include emulsifying and surface-active agents, emollients, perfumes, dyes, anti-oxidants, preservatives, other common solvents, e.g. lower alcohols, inorganic and organic acids, water-soluble salts, germicides, e.g. hexachlorophene, antibiotics, steroids, deodorants, thickening agents, skin restoratives, e.g. allantoin and rejuvanaters, humectants and opacifiers.  Preparations of compositions according to the invention are described.
Provided are a disialoganglioside 2 (GD2) chimeric antigen receptor (CAR) and use thereof. A humanized GD2 single-chain variable fragment (scFv) antibody has activity of binding to a GD2 antigen, where the humanized GD2 scFv has a more than 80%of amino acid sequence identity with SEQ ID NO. 1. Further provided are the GD2 CAR and a chimeric antigen receptor T (CAR-T) cell expressing the GD2 CAR. The humanized GD2 scFv has better bioactivity and compatibility. Binding the GD2 CAR to GD2 has a better response effect, a stronger immune response and a better long-term effect. The CAR-T cell has higher safety and persistence and an extremely high application value.
Researchers at the intersection of sleep and suicide research have advocated for investigation of sleep disturbances as a therapeutic target for the purposes of treating and preventing suicide. This study aims to provide the first systematic review and meta-analysis on the efficacy of sleep interventions to treat suicidal ideation. This systematic review and meta-analysis, registered with the International Prospective Register of Systematic Reviews, was conducted in PsycINFO, through Ovid. A sample of eight articles were deemed eligible and a total of 21 effect sizes were included. Egger's test suggested that no publication bias was present (b = 0.3695; p = 0.0852). The pooled effect size for sleep treatments on suicidal ideation was small (g = -0.0931, p = 0.3047). Significant heterogeneity was present (I2 = 44.13%), indicating the need for moderator analyses. Treatment type (medication versus psychotherapy; g = -0.2487, p = 0.3368), sex (g = -0.0007; p = 0.9263), and race (g = -0.0081; p = 0.1624) were all considered as moderators and were all found to be insignificant. This meta-analysis revealed that initial studies exploring the efficacy of sleep interventions on suicidal ideation demonstrate small effect sizes. Despite this, the handful of studies included in this review nonetheless highlight this as an important area for continued exploration. The use of larger and more diverse samples, as well as intentionally designing sleep-related interventions to improve ideation and behaviour, have the potential to enhance the efficacy of sleep interventions for this novel purpose.
BACKGROUND/AIMS: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.
METHODS: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).
RESULTS: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.
CONCLUSION: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.
Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases.
New methods have been developed to treat obesity or other human disorders by increasing the degree of brown adipose thermogenesis, by both increasing the growth and differentiation of brown adipose tissue and increasing its activity. A new use for the transcription factor NFE2l2 was developed to increase BAT thermogenesis by increasing the expression of Ucp1. For the first time, NFE2l2 was found to interact with the NF-E2 motif and to stimulate the expression of Ucp1 (Figure 9). By modulating the expression of the Nfe2l2 gene or the concentration of NFE2l2 protein, changes in brown adipose tissue thermogenesis can be achieved to treat various weight disorders. Additionally, the direct involvement of CREB binding to CRE2 to regulate Ucp1 expression was demonstrated. Furthermore, transient transfection assays of luciferase reporter constructs and site-directed mutagenesis indicated that CRE2 was involved in transcriptional regulation of the Ucp1 through interaction with a phosphorylated CREB. NFE2l2 can be combined with other known transcription factors, e.g., CREB, PGC1, RXR, RAR, and PPAR gamma, to increase BAT thermogenesis by increasing the expression of Ucp1.
BACKGROUND: While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study.
METHODS: We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes.
RESULTS: Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production.
CONCLUSIONS: Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.
Natural products (NP) have been an alternative therapy for several diseases for centuries, and they also serve as an essential source of bioactive molecules, enhancing our drug discovery capacity. Among these NP, some phytochemicals have shown multiple biological effects, including anticancer activity, with higher effectiveness and less toxicity than actual treatments, suggesting their possible use on resilient human malignancies such as leukemia. Imatinib mesylate (Im) is a selective tyrosine kinase inhibitor widely used as an anticancer drug, the gold standard to attend chronic myeloid leukemia (CML). Nevertheless, resistance to this drug in patients with CML renders it insufficient to eliminate cells with Philadelphia chromosome (BCR/ABL+). Moreover, recent studies show that imatinib can induce genotoxic and chromosomic damage in some in vitro and in vivo models. These facts urge finding new therapeutic alternatives to increase the effectiveness of antileukemic treatment. Recent research has shown that the combined effects of phytochemicals with imatinib can improve the cytotoxicity or resensitized the resistant cells to this drug in diverse leukemia cell lines. Independent mechanisms of action among phytochemicals and imatinib include BCR/ABL regulation, downregulation of transcription factors, inhibition of anti-apoptotic and activation of pro-apoptotic proteins, apoptosis induction dependent- and independent of ROS-overproduction, membrane functions disruption, induction of cell cycle arrest, and cell death. This review summarizes and discusses the synergic effect of some phytochemicals combined with imatinib on leukemia cells and the mechanism of action proposed for these combinations, looking to contribute to developing new effective alternatives for leukemia treatment.
A diagnostic method for assessing how a hypercholesterolemic person's serum cholesterol level will respond to a low total fat and saturated fat diet. The method involves defining a target cholesterol level, measuring a baseline level, feeding for a term of 3-25 days a NCEP Step I diet of which at least 50% of the caloric intake is provided by a fortified, low-fat nutritional product, and comparing the post term cholesterol level to the defined goal to see if the target is met. If the target is met, the person is predicted to respond to dietary intervention. If the target is not met, the person is deemed a non-responder and is considered for drug therapy. A fortified, low-fat nutritional product supplies in about 1000 kcal (i) 100% of the adult RDI for vitamins and minerals; and (ii) total fat, saturated fat and cholesterol levels that are at or below the levels specified for a Step II diet. Preferably the total fat comprises 25% or less of total calories; and the saturated fat and cholesterol maximum levels are less than about 2-3% of total calories in the case of saturated fat, and less than about 30-50 mg per 1000 kcal in the case of cholesterol.
BACKGROUND: In intermediate/high risk prostate cancer, preoperative staging exams are mandatory. The aim of these imaging studies is to evaluate eventual lymph nodes involvement and/or metastatic spread of the tumor. Nevertheless, computed tomography (CT), magnetic resonance imaging (MRI), bone scan modalities have controversial sensitivity. Introduction of PET-PSMA and its use also as preoperative exam, seems to improve diagnostic accuracy due to favorable negative predictive value. The aim of this study was to evaluate the accuracy of PET-PSMA as a preoperative staging exam and its accuracy in predicting lymph nodes involvement in intermediate/high risk prostate cancer (PCa) patients.
METHODS: A retrospective analysis of 50 patients diagnosed with intermediate/high risk PCa between 2018 and 2022 has been performed. All patients underwent preoperative 68Ga-PSMA PET/CT prior to robot-assisted radical prostatectomy (RARP) + extended pelvic lymph node dissection (ePLND). The cohort was categorized into two groups: pathologically negative lymph nodes (pN0) vs. positive nodes (pN1). A descriptive and comparative analysis was conducted. Correlation analysis between continuous variables was performed using the Spearman's Rank Test. Using lymph nodes histopathological results as reference standard, the diagnostic performance of 68Ga-PSMA PET/CT was calculated.
RESULTS: Overall, 50 patients were included. The mean age was 63.3 years with a median prostatic specific antigen (PSA) of 7.7 ng/dL. Forty-four percent of the patients exhibited an International Society of Urological Pathology (ISUP) score of 4 or higher, and 28% had a pT3 stage. Overall, 43 (86%) patients submitted to ePLND did not present lymph node metastases (pN0), while 8 (14%) patients were pN1. PET-PSMA showed low sensitivity in detecting lymph node metastases (25%) while a high specificity in excluding lymph-node disease (88.1%) has been observed. Finally, we noted a significant positive correlation between the total SUV<inf>max</inf> of the prostate and the initial total PSA (r=0.38; P=0.019), as well as the percentage of tumor involvement (r=0.383; P=0.022).
CONCLUSIONS: Evidence on the role of PET-PSMA in the primary staging of PCa is steadily building up. A positive correlation between SUV and prostate involvement indicates that PET-PSMA could reflect, with a good approximation, the pathological features of the prostate. However, the low sensitivity depicted remains the main limitation. Future prospective studies are needed to determine the impact on patient outcome.