anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear. We found that although high-fat diet treatment in mice elevated both 7-oxo-DCA and isoDCA levels, during intestinal tumorigenesis, 7-oxo-DCA levels rise while isoDCA levels decrease. Interestingly, 7-oxo-DCA promotes cancer cell growth, while isoDCA suppresses it. Moreover, 7-oxo-DCA promotes whereas isoDCA inhibits the proliferation of intestinal stem cells in organoids derived from WT and APCMin/+ mice, as well as in patient-derived colon cancer organoids. The APCMin/+ mice administered with 7-oxo-DCA heightened gut permeability and increased tumor burden, whereas isoDCA protected gut barrier and reduced tumor loads. Both BAs reshape the BA pool and shifted gut microbiome. Mechanistically, we identified 7-oxo-DCA as a natural antagonist of Farnesoid X Receptor (FXR) to downregulate FXR signaling, as opposed to isoDCA, which is a potent FXR agonist to upregulate FXR signaling. In conclusion, we unveiled the opposing roles of 7-oxo-DCA and isoDCA to promote or inhibit intestinal tumorigenesis, respectively. Manipulating the BA-FXR axis during tumor initiation and progression holds great promise for developing innovative diagnostic and therapeutic approaches for the treatment of colorectal cancer.
GP trainees in this arm will continue with training as usual and will have their prescribing (approximately 200 prescriptions) reviewed once but representing two time points - separated by an approximate 3-month time period. Feedback will occur at one time point, to cover the review for the 200 prescriptions.
The group with the combined training receives 5 sessions of CT and EET each. The pattern of series per week is always either two sessions of CT with one session of EET or vice versa.
1410541 Concentrating biological heatsensitive substances BAYER AG 4 Jan 1973 [1 Feb 1972] 497/73 Heading B1G Solutions of biological heat sensitive substances selected from enzymes, enzyme-inhibitors, natural or synthetic antibiotics, and intermediate products used in the production of antibiotics are concentrated by (i) cooling the impure solution to produce two separate portions consisting of a frozen impure solution a cooled impure solution (ii) mixing product (i) with ice to form pure ice crystals and a first concentrated solution and (iii) separating the pure ice crystals from the concentrated solution. The production of the frozen solution is preferably effected in a rotary cooling device at about -40C. The process also includes (iv) further cooling the concentrated solution to form ice and a second concentrated solution and (v) separating ice from step (iv) and recycling the latter to step (ii). Specified substances are kallikrein, hyaluronidase, asparaginase, kallikein-trypsin inhibitor, pancreas extracts, 6-aminopenicillanic acid and semi-synthetic penicillins manufactured therefrom. The process may be carried out batchwise or continuously. The Figure shows a flow diagram of a preferred process wherein the impure solution 10 is pre-cooled in precooler (1) and partially frozen in rotary freezing device (2) at about -40C and the frozen solution scraped off as scales and mixed in crystallizer 3, with pre-cooled impure solution 10 and with ice recycled from second separation device 6. After completion of recrystallization in 3, pure ice crystals are separated from the first concentrated solution 12 in the first separating device 4. The recycled pure ice 11, is used to pre-cool impure solution 10, in the pre-cooler 1 and is then discarded. The first concentrated solution obtained is fed to device 5 wherein it is further concentrated and separated in device 6 into concentrated solution 13 and ice crystals.
A vapor viable formula for sanitizing the lungs in order to shield them from a digitally encoded pathogen. The digital code translates into 2 and 3 dimensional proteins capable of self-replicating in the host. Agent(s) can traverse the semipermeable membranes of the host cells in order to specifically target the translated proteins in a 2-dimensional state before they fold into a functional 3-dimensional molecule. The agent(s) must be able to disable the 3-dimensional functional analog state of a pathogen component. 2-Propene-1-sulfinothioic acid S-2-propenyl or an R group derivative thereof is formulated so that it can be put into vapor form and inhaled into the sinuses, throat, bronchi, or lungs with maximum surface bioavailability. Selenium or Selenocysteine exploits of the digital pathogen code are leveraged using vapor formulas. Vapor delivery allows maximum analog or digital exploitation of the pathogen.
INTRODUCTION: Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear.
METHODS: This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR-Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.
RESULTS: Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.
CONCLUSION: Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.
INTRODUCTION: Predicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data.
METHOD: The ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model.
RESULTS: Nine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes.
CONCLUSION: The model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.
FIELD: medicine. ^ SUBSTANCE: medication for photodynamic therapy (PDT) includes photosensitising substance based on hydrophilic chlorine E6 derivative, phosphatidylcholine, cholesterol, citric acid and saccharose with definite molar component ratio. Method of obtaining said medication includes dissolution of phosphatidylcholine and cholesterol in chloroform, mixing said solutions and further evaporation under vacuum until formation of film, which is dispersed with water solution of chlorine E6 derivative into liposomal dispersion. After that, into liposomal dispersion water solution of saccharose and citric acid with pH 5.0 is added and lyophilised, and immediately before intravenous introduction redispersed with application of distilled water or physiological solution. Method of carrying out PDT lies in systemic introduction of claimed medication and irradiation of pathologic section 4-5 hours after its introduction with optic irradiation, absorbed by chlorine E6. Claimed method of obtaining medication for PDT ensured increase of chlorine E6 derivative inclusion into said medication, increase of its stability in long storage and increase of its technological output. ^ EFFECT: high efficiency of photodynamic therapy and selectiveness of accumulation. ^ 3 cl, 4 dwg, 3 ex
Delirium is an acute-onset brain dysfunction related to extensive surgery or critical illness that leads to altered mental status and cognitive deficits. Delirium is associated with an increased length of stay in the ICU, cost of care, excessive mortality, and long-term cognitive and functional impairment. Although numerous prophylactic methods have been proposed, currently, no pharmacological or non-pharmacological methods are clinically effective. Patients with delirium have altered electroencephalography (EEG) findings among which most important are general slowing of EEG frequencies and dysconnectivity. Faster EEG frequencies, especially alpha-, beta-, and gamma-bands, are correlated with higher cognitive functions, such as memory and orientation. Transcranial alternating current stimulation (TACS) is a novel, noninvasive brain stimulation technology that cab modulate EEG frequencies by entraining of endogenous brain oscillations in response to exogenous stimuli. TACS has been shown to improve episodic memory, orientation, and cholinergic dysfunction in patients with Alzheimer's disease. TACS also increases alpha and gamma frequencies in EEG, and an increase in these frequencies is associated with the improvement of clinical symptoms. TACS has been shown to target key components of delirium pathophysiology, such as slowing of EEG frequencies and cholinergic dysfunction. Thus, we hypothesized that TACS could shorten the duration of delirium and decrease cognitive decline. We aim to test this hypothesis in a double-blind randomized trial and assess the effect of TACS on duration of delirium, EEG, biomarkers and long-term cognition.
This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL. The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences. HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045). The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.
This article presents the rare case of a 54-year-old gentleman with primary glioblastoma developing multiple extracranial metastases 7 months after diagnosis. Initially, the patient complained of progressive headaches, confusion, and weakness of the left arm. Magnetic resonance imaging of the brain showed a right temporoparietal tumor with substantial surrounding subcortical edema and midline shift to the left. Two consecutive craniotomies resulted in complete microsurgical resection of the lesion. Histology was consistent with a World Health Organization grade IV, IDH-wildtype glioblastoma. Further treatment was standard chemoradiation including intensity-modulated radiotherapy with oral temozolomide chemotherapy. Seven months after diagnosis, the cranial lesion progressed, and the patient developed painful metastases in multiple bones and suspicious right-sided cervical lymph nodes. Immunohistochemistry and molecular signature supported the case of a metastatic glioblastoma. Further treatment was palliative radiotherapy of the spinal lesions along with symptomatic pain management. Extracranial metastasis of glioblastoma is a rare complication of which only a few cases have been reported in the literature. Little is known about the precise mechanisms of tumor dissemination and the appropriate treatment.
A narrowing of the aortic valve, aortic stenosis, is a relatively common condition among the elderly. When the narrowing gets too severe, symptoms such as loss of breath, angina and fainting can occur, so called symptomatic aortic stenosis. Since the 60's, surgical aortic valve replacement (sAVR) has been the treatment of choice for severe aortic stenosis. A large setback of this method is that a third of these patients could not undergo the treatment due to too high surgical risk.

Transcatheter aortic valve implantation (TAVI) have steadily gained ground in the treatment of severe aortic valve stenosis during the last decade. The procedure, which is a minimal invasive type of surgery, introduces a new aortic valve through a catheter, usually transfemorally. Patients with an underlying coronary artery disease (CAD) undergoing sAVR is known to have higher mortality rates postoperatively. However, it is not clearly known how an underlying CAD affects the long term results after a TAVI-surgery. It is therefore our goal to contribute with the mapping of how a CAD affects the long term results for patients with a severe aortic valve stenosis that undergoes TAVI.
All youth enrolled in the study will receive the 6-month MyPlan behavioral intervention. Youth and their guardian will be paired with a dietitian to individualize the eating pattern and receive support in setting and refining action plans focused on adhering to the five eating behavior goals that define the eating pattern.
PROBLEM TO BE SOLVED: To obtain a composition for the oral cavity, useful for preventing dental caries and periodontosis and causing a low level of discoloration with time. SOLUTION: This composition for the oral cavity is obtained by blending 0.1-20wt.% polyoxyethylene hardened castor oil and 0.01-2wt.% metallic salt of copper chlorophyllin (e.g. sodium copper chlorophyllin) in a composition for the oral cavity containing 0.001-5wt.% green tea extract. The green tea extract is prepared by pulverfzing a dried green tea leaf, extracting the pulverized and dried green tea leaf with water or an alcohol at ambient temperature, distilling away the solvent from the extract solution, then adding water thereto, dissolving the resultant residue, reextracting the obtained solution with a nonpolar organic solvent (e.g. ethyl acetate) and drying and powdering the resultant extract solution separated with the nonpolar organic solvent.  Furthermore, usually used various additives are suitably blended therewith according to the kind of the composition for the oral cavity and prepared into a dentifrice, a mouthwash, a refreshing agent in the mouth, a troche, a pasta agent, a chewing gum, a candy, etc.
BACKGROUND: Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with persistent spinal pain syndrome with previous spinal surgery (PSPS-T2) or ineligible for it (PSPS-T1). This study reports 24-month efficacy and safety of DTM SCS vs. conventional medical management (CMM) in PSPS-T1 subjects across four European countries.
METHODS: This is a prospective, multicenter, open-label, randomized, controlled trial with optional crossover. Subjects randomized 1:1 to DTM SCS or CMM. Primary endpoint was responder rate (% subjects reporting ≥50% CLBP relief) at 6 months. A superiority test compared responder rates between treatments. CLBP and leg pain levels, functional disability, quality of life (QoL), patient satisfaction and global impression of change were evaluated for 24 months. A Composite Responder Index (CRI) was obtained using CLBP relief, disability and QoL. Incidence of study-related adverse events evaluated safety.
RESULTS: A total of 55 and 57 subjects were randomized to DTM SCS and CMM respectively. DTM SCS was superior, with CLBP responder rates ≥80% and CLBP relief >5.6 cm (>70% reduction) through the 24-month follow-up. Improvements with DTM SCS in other outcomes were sustained. The CRI was >80% for DTM SCS through 24 months. Opioid medication intake decreased in subjects treated with DTM SCS. Most patients treated with DTM SCS felt satisfied and improved at the end of the study. Safety was congruent with other studies.
CONCLUSION: DTM SCS is efficacious and safe during 24 months for the treatment of CLBP and leg pain in PSPS-T1 patients ineligible for spine surgery.
SIGNIFICANCE STATEMENT: This randomized controlled trial shows that Differential Target Multiplexed SCS (DTM SCS) is an effective and safe long-term treatment for PSPS type 1 patients suffering from axial low back pain with or without leg pain and who are ineligible for spinal surgery. Currently, CMM treatments are their only option and provide limited benefits. Besides superior pain relief, DTM SCS provides significant improvements in functional disability, quality of life, high levels of satisfaction and perceived impression of change.
After taking off the electrophysiological monitoring from the patients, discontinue propofol and start desflurane from 6% (dialed concentration) at flow rate of 4L/min for 2 minutes in desflurane group. When achieve end tidal concentration of 4-5%, decrease the flow rate to 2L/min.
The purpose of this Phase Ib study is to test the safety of NG-monomethyl-L-arginine (L-NMMA) and pembrolizumab when used together in participants with melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), urothelial carcinoma, Cervical Cancer, Esophageal Cancer, Gastric Cancer, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Primary Mediastinal Large B-cell Lymphoma, Renal Cell Carcinoma, Small Cell Lung Cancer, microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) cancer or for the Treatment of Adult Patients with Unresectable or Metastatic Tumor Mutational Burden-High Solid Tumors. Pembrolizumab is a type of treatment that stimulates the immune system to attack cancer cells. The immune system is normally the body's first defense against threats like cancer. However, sometimes cancer cells produce signals like PD-L1 that prevent the immune system from detecting and killing them. Pembrolizumab blocks programmed death-1 (PD-1) so your immune system can detect and attack cancer cells. To help further boost the cancer-fighting ability of your immune system, L-NMMA will be used along with pembrolizumab. L-NMMA is a nitric oxide synthase inhibitor. The presence of nitric oxide synthase in the area around the cancer cells blocks the cancer-fighting ability of the immune system. Thus, the use of L-NMMA and pembrolizumab together may make the immune system work harder to attack and destroy the cancer cells.

In this study, up to 3 different doses of L-NMMA will be studied (12.5, 15, and 20 mg/kg). Participants will only receive one of the three L-NMMA doses. The first several study participants will receive the 15 mg/kg dose. If the 15 mg/kg dose of L-NMMA causes serious side effects, L-NMMA will be given to other study participants at the lower dose of 12.5 mg/kg. If the 15 mg/kg dose of L-NMMA does not cause serious side effects, L-NMMA will be given to other study participants at the higher dose of 20 mg/kg. All study participants will be given the same dose of pembrolizumab (200 mg). This study will allow us to see the highest dose of L-NMMA that can be used safely with pembrolizumab in participants with melanoma, NSCLC, HNSCC, cHL, urothelial carcinoma, or MSI-H/dMMR cancer.
Patients with endoscopically detected Upper Gastrointestinal Submucosal Tumors with diameter ≥ 2cm are, according to randomization, allocated to undergo esophagogastroduodenoscopy with Key Hole Biopsy consisting of forceps biopsy through mucosal incision by a needle knife, with subsequent cytological /histological and immunohistochemical evaluation of specimen. In the case of Gastrointestinal Stromal Tumors (GIST), the possibility to determine the mitotic activity is evaluated.
For resting myocardial studies, begin imaging 10 to 20 minutes after injection of Thallous Chloride Tl 201. Myocardial-to-background ratios are improved when patients are injected upright and in the fasting state; the upright position reduces the hepatic and gastric thallium Tl-201 concentration.

For exercise stress testing administer Thallous Chloride Tl 201 Injection at the start of a period of maximum stress which is sustained for approximately 30 seconds after injection. Begin imaging within ten minutes after administration to obtain maximum target-to-background ratios. Within two hours after the completion of the stress testing the target-to-background ratios may decrease in lesions that are attributable to transient ischemia.

For localization of parathyroid hyperactivity, administer Thallous Chloride Tl 201 Injection before, with or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc 99m or sodium iodide I-123 to enable thyroid subtraction imaging.
Patients with invasive breast cancer diagnosed by core needle biopsy (CNB) and not to receive neoadjuvant system therapy are eligible for this study. ER, PR, Her-2 and Ki67 are determined by immunohistochemistry (IHC) in CNB and surgical specimen. FISH analysis will be carried out in all HER2 2+ samples.