anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Obesity activates both innate and adaptive immune responses in adipose tissue. Adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-γ)-producing cluster of differentiation (CD)4+ T cells in adipose tissue of obese subjects. The increased formation of neopterin and degradation of tryptophan may result in decreased T-cell responsiveness and lead to immunodeficiency. The activity of inducible indoleamine 2,3-dioxygenase-1 (IDO1) plays a major role in pro-inflammatory, IFN-γ-dominated settings. The expression of several kynurenine pathway enzyme genes is significantly increased in obesity. IDO1 in obesity shifts tryptophan metabolism from serotonin and melatonin synthesis to the formation of kynurenines and increases the ratio of kynurenine to tryptophan as well as with neopterin production. Reduction in serotonin (5-hydroxytryptamine; 5-HT) production provokes satiety dysregulation that leads to increased caloric uptake and obesity. According to the monoamine-deficiency hypothesis, a deficiency of cerebral serotonin is involved in neuropsychiatric symptomatology of depression, mania, and psychosis. Indeed, bipolar disorder (BD) and related cognitive deficits are accompanied by a higher prevalence of overweight and obesity. Furthermore, the accumulation of amyloid-β in Alzheimer's disease brains has several toxic effects as well as IDO induction. Hence, abdominal obesity is associated with vascular endothelial dysfunction. kynurenines and their ratios are prognostic parameters in coronary artery disease. Increased kynurenine/tryptophan ratio correlates with increased intima-media thickness and represents advanced atherosclerosis. However, after bariatric surgery, weight reduction does not lead to the normalization of IDO1 activity and atherosclerosis. IDO1 is involved in the mechanisms of immune tolerance and in the concept of tumor immuno-editing process in cancer development. Serum IDO1 activity is still used as a parameter in cancer development and growth. IDO-producing tumors show a high total IDO immunostaining score, and thus, using IDO inhibitors, such as Epacadostat, Navoximod, and L isomer of 1-methyl-tryptophan, seems an important modality for cancer treatment. There is an inverse correlation between serum folate concentration and body mass index, thus folate deficiency leads to hyperhomocysteinemia-induced oxidative stress. Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated protein-4 synergizes with imatinib, which is an inhibitor of mitochondrial folate-mediated one-carbon (1C) metabolism. Antitumor effects of imatinib are enhanced by increasing T-cell effector function in the presence of IDO inhibition. Combining IDO targeting with chemotherapy, radiotherapy and/or immunotherapy, may be an effective tool against a wide range of malignancies. However, there are some controversial results regarding the efficacy of IDO1 inhibitors in cancer treatment.
PCT No. PCT/EP95/03993 Sec. 371 Date Nov. 18, 1997 Sec. 102(e) Date Nov. 18, 1997 PCT Filed Oct. 10, 1995 PCT Pub. No. WO96/37209 PCT Pub. Date Nov. 28, 1996The invention relates to methods for preventing, inhibiting, or suppressing tumors by administering to a person in need of such treatment a therapeutically effective amount of one or more flavanolignanes, such as silymarin, silybin, silidianin, silicristin, dehydrosilybin, mixtures thereof, or extracts thereof as an antiproliferative. The invention further relates to the antitumor pharmaceutical composition includes a therapeutically effective amount of the flavanolignane selected from the group of silymarin, silybin, silidianin, silicristin, dehydrosilybin, and mixtures thereof, in combination with a different antitumor agent. In another embodiment, the pharmaceutical composition includes a therapeutically effective amount of a flavanolignane selected from the group of silidianin, silicristin, and mixtures thereof, with a pharmaceutically acceptable carrier or excipient. The compositions and method may be prepared or administered with different antitumoral agents for concurrent or sequential use for treating tumors, such as those typically found in the uterus, ovary, and breast.
Substances diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate and products containing St. John’s wort. Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone concentrations.

Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of the estrogen and progestin have been noted in some cases of co-administration of HIV/HCV protease inhibitors or of non-nucleoside reverse transcriptase inhibitors. 

Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.
Background and Objectives: Axillary lymph node (ALN) staging is crucial for the management of invasive breast cancer (BC). Although various radiological investigations are available, ultrasound (US) is the preferred tool for evaluating ALNs. Despite its immediacy, widespread use, and good predictive value, US is limited by intra- and inter-operator variability. This study aims to evaluate US and Elastosonography Shear Wave (SW-ES) parameters for ALN staging to develop a predictive model, named the Cassandra score (CS), to improve the interpretation of findings and standardize staging. Materials and Methods: Sixty-three women diagnosed with BC and treated at two Italian hospitals were enrolled in the study. A total of 529 lymph nodes were surgically removed, underwent intraoperative US examination, and were individually sent for a final histological analysis. The study aimed to establish a direct correlation between eight US-SWES features (margins, vascularity, roundness index (RI), loss of hilum fat, cortical thickness, shear-wave elastography hardness (SWEH), peripheral infiltration (PI), and hypoechoic appearance) and the histological outcome (benign vs. malignant). Results: Several statistical models were compared. PI was strongly correlated with malignant ALNs. An ROC analysis for Model A revealed an impressive AUC of 0.978 (S.E. = 0.007, p < 0.001), while in Model B, the cut-offs of SWEH and RI were modified to minimize the risk of false negatives (AUC of 0.973, S.E. = 0.009, p < 0.001). Model C used the same cut-offs as Model B, but excluded SWEH from the formula, to make the Cassandra model usable even if the US machine does not have SW-ES capability (AUC of 0.940, S.E. = 0.015, p < 0.001). A two-tiered model was finally set up, leveraging the strong predictive capabilities of SWEH and RI. In the first tier, only SWES and RI were evaluated: a positive result was predicted if both hardness and roundness were present (SWES > 137 kPa and RI < 1.55), and conversely, a negative result was predicted if both were absent (SWES < 137 kPa and RI > 1.55). In the second tier, if there was a mix of the results (SWES > 137 kPa and RI > 1.55 or SWES < 137 kPa and RI < 1.55), the algorithm in Model B was applied. The model demonstrated an overall prediction accuracy of 90.2% in the training set, 87.5% in the validation set, and 88.9% across the entire dataset. The NPV was notably high at 99.2% in the validation set. This model was named the Cassandra score (CS) and is proposed for the clinical management of BC patients. Conclusion: CS is a simple, non-invasive, fast, and reliable method that showed a PPV of 99.1% in the malignancy prediction of ALNs, potentially being also well suited for young sonographers.
BACKGROUND: Septic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors.
METHODS: This study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors.
DISCUSSION: This protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making.
TRIAL REGISTRATION: This clinical trial has been registered at ChiCTR ( https://www.chictr.org.cn/ ) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.
A viral symbiont (CPV) of Cryptosporidium parvum and Cryptosporidium hominis sporozoites has been characterized and a CPV capsid protein, CPV40, has been identified as a target for sensitive detection of C. parvum. Recombinant CPV40 was produced in E. coli, purified by affinity chromatography, and used to prepare polyclonal rabbit sera specific for the viral capsid protein. Anti-rCPV40 recognized a 40 kDa and a 30 kDa protein in C. parvum oocysts and appeared to localize to the apical end of the parasite. Anti-rCPV40 serum was capable of detecting as few as one C. parvum or C. hominis oocyst in a dot blot assay, the sensitivity being at least 1000-fold greater than sera reactive with total native C. parvum protein or specific for the 41 kDa C. parvum oocyst surface antigen. Water samples were seeded with C parvum oocysts and incubated at 4, 20, or 25 °C for greater than 3 months to determine if CPV levels were correlated with oocyst infectivity and viral particle presence. While sporozoite infectivity declined by more than 75% after 1 month at 25 °C, the CPV signal was similar to that of control samples at 4 °C. By three months at 20 °C, the C. parvum oocysts were found to be non-infectious, but retained a high CPV signal. CPV is an excellent target for sensitive detection of C. parvum and C. hominis oocysts in water, but may persist for an indefinite time after oocysts become non-infectious.
A scaffold for promoting cartilage formation is provided that includes a crosslinked electrospun fiber, wherein the crosslinked electrospun fiber consists essentially of crosslinked gelatin. The crosslinked electrospun fiber is generally crosslinked with a crosslinker, and the crosslinker may be diisosorbide bisepoxide. The crosslinked electrospun fiber may be crosslinked by adding a crosslinker to a solution of gelatin at a desired concentration. The electrospun fiber may advantageously remain intact for 18 days or longer upon being immersed in an aqueous solution. A composition for promoting cartilage formation is also provided that includes the disclosed scaffold and a mesenchymal stem cell (MSC). The disclosed scaffold may include a crosslinked electrospun fiber that includes gelatin and sodium cellulose sulfate (NaCS), e.g., in an amount of up to 5% by weight of the amount of gelatin. A method for promoting cartilage formation is also provided that includes administering to a subject in need thereof a disclosed composition for promoting cartilage formation in the subject.
OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A).
METHODS: A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children's Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing.
RESULTS: The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c.1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously.
CONCLUSION: The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.
Nateglinide is rapidly absorbed and stimulates pancreatic insulin secretion within 20 minutes of oral administration. When nateglinide is dosed three times daily before meals there is a rapid rise in plasma insulin, with peak levels approximately 1 hour after dosing and a fall to baseline by 4 hours after dosing.

In a double-blind, controlled clinical trial in which nateglinide was administered before each of three meals, plasma glucose levels were determined over a 12-hour, daytime period after 7 weeks of treatment. Nateglinide was administered 10 minutes before meals. The meals were based on standard diabetic weight maintenance menus with the total caloric content based on each subject’s height. Nateglinide produced statistically significant decreases in fasting and postprandial glycemia compared to placebo.
Compositions and methods of treating hyperglycemia in a subject having such a condition are disclosed. An inhibitor compound which causes activity of Cullin RING E3 ligases (CRL) to be reduced is administered to the subject, wherein blood glucose concentration is decreased. The inhibitor compound is optionally administered as an inhibitor composition comprising a pharmaceutically-acceptable carrier, vehicle, or diluent. Impaired function of Insulin receptor substrate (IRS) proteins in diabetes contributes significantly to insulin resistance in various insulin responsive organs including liver, muscle, and adipose. Cullin RING E3 ligases (CRLs) are a sub-class of ubiquitin ligases that have been shown to mediate IRS protein degradation in cells. Inhibition of CRL activity, e.g., by decreasing cullin neddylation by inhibiting NEDD8-activating enzyme (NAE), or decreasing cullin activity, e.g., by inhibiting expression of cullins, is shown herein to delay IRS protein turnover in liver cells and muscle cells, thereby increasing cellular response to insulin and decreasing blood glucose. Thus, inhibition of CRLs, for example by inhibiting neddylation, is an effective method to treat hyperglycemia and insulin resistance in patients with type-2 diabetes.
Subjects will take GSK1278863 6 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24.
The present invention relates to methods of treating cancer in a subject by administering to the subject a combination of an oncolytic virus and a therapy that induces depletion of tumor-induced polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). In certain preferred embodiments, the oncolytic virus is a modified vaccinia Temple (MVTT) virus having a replication defect with a deletion in the M1L-K2L gene of the virus. In other preferred embodiments, the therapy that induces tumor-induced depletion of PMN-MDSCs comprises administration of an antibody against Ly6G, e.g., 1a 8. The cancer therapies of the invention can be administered in combination with one or more other anti-cancer therapies. Preferred additional anti-cancer therapies are immunotherapy, e.g. administration of checkpoint inhibitors.
OBJECTIVE: Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment.
DESIGN: We identified TLR8-expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN's indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN's effect were validated using transcriptomic data from HBV-infected patients.
RESULTS: Hepatic TLR8 expression takes place in the myeloid compartment. SLGN treatment of KCs upregulated monocyte markers (eg, S100A12) and downregulated genes associated with the KC identity (eg, SPIC). Treatment of hepatocytes with SLGN-CM downregulated NTCP and impaired HBV entry. Cotreatment with an interleukin 6-neutralising antibody reverted the HBV entry inhibition.
CONCLUSION: Our transcriptomic characterisation of SLGN sheds light into the programmes regulating KC activation. Furthermore, in addition to its previously described effect on established HBV infection and adaptive immunity, we show that SLGN impairs HBV entry. Altogether, SLGN may contribute through KCs to remodelling the intrahepatic immune microenvironment and may thus represent an important component of future combinations to cure HBV infection.
With the continuous progress of technology, the subject of life science plays an increasingly important role, among which the application of artificial intelligence in the medical field has attracted more and more attention. Bell facial palsy, a neurological ailment characterized by facial muscle weakness or paralysis, exerts a profound impact on patients' facial expressions and masticatory abilities, thereby inflicting considerable distress upon their overall quality of life and mental well-being. In this study, we designed a facial attribute recognition model specifically for individuals with Bell's facial palsy. The model utilizes an enhanced SSD network and scientific computing to perform a graded assessment of the patients' condition. By replacing the VGG network with a more efficient backbone, we improved the model's accuracy and significantly reduced its computational burden. The results show that the improved SSD network has an average precision of 87.9% in the classification of light, middle and severe facial palsy, and effectively performs the classification of patients with facial palsy, where scientific calculations also increase the precision of the classification. This is also one of the most significant contributions of this article, which provides intelligent means and objective data for future research on intelligent diagnosis and treatment as well as progressive rehabilitation.
Patients with recurrent or metastatic nasopharyngeal carcinoma who failed to first-line platinum-based chemotherapy and had prior treatment with PD-1 antagonists. Every patients will receive apatinib 250mg orally every day starting 14 days prior to Camrelizumab. Then apatinib 250mg orally every day and Camrelizumab 200mg iv every 3 weeks until disease progression or intolerance of side effects.
The invention discloses a medicine composition, a preparation method thereof, preparation and application. The medicine composition consists of radix notoginsengs, Yunnan fallopia multiflora, salvia miltiorrhiza and hawthorns, wherein the weight ratio is (0.5-1.5):( 0.5-1.5):(0.5-1.5):(0.5-1.5). The preparation method comprises the working procedures of preprocessing, coarse grinding, superfine grinding and mixing. The preparation is powder, tablets, granules, capsules, dripping pills or honey pills prepared by adding pharmaceutically acceptable auxiliary materials into the medicine composition. The medicine composition is applied to preparation of medicines for lowering blood pressure and blood fat. The medicine composition is prepared through mixing according to precisely set composition, achieves the effect of lowering blood pressure and blood fat according to physical and chemical properties of the raw medicines and compatibility of contained active ingredients and has the advantages of being high in bioavailability, fast in active ingredient dissolution, good in medicine absorption effect and small in side effect.
A process for the solvent fractionation of palm oil stearine or of catalytically rearranged palm oil stearine, or other stearines from animal or vegetable sources into three fractions of widely different physical properties is described. One fraction is composed of high melting triglycerides (hard fat fraction), which melt from 45-65°C. A second fraction is composed of somewhat lower melting triglycerides which melt from 33-44°C (the confectionery fat fraction). The third fraction is composed of low melting triglycerides and is an oil at room temperature. The major value of these fractions is their ability to function as food components but they have numerous non-food uses particularly in cosmetics and pharmaceuticals. Their utility is not restricted to their individual use but on the contrary their usefulness may be tremendously increased by using them in combinations of two or more fractions or with other fatty materials.