anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.
The invention discloses an active fraction in rose odorata sweet vat.gogantea(coll.et hemsl.)rehd.et wils for treating diarrhea and a preparation method thereof. The preparation method comprises the following steps of: (1) extracting: adding rose odorata sweet vat.gogantea(coll.et hemsl.)rehd.et wils serving as a raw material into an acid aqueous solution, soaking and extracting at 60-80 DEG C for 2-3 times every time for 6-8 hours, and sieving with a sieve of 80-120 meshes to obtain an extracting solution; and (2) adsorbing the product obtained in the step (1) with macroporous resin, eluting with water and an ethanol aqueous solution, removing a water eluent, collecting an ethanol eluent, concentrating the eluent under reduced pressure to obtain a concentrate, and drying to obtain the active fraction in rose odorata sweet vat.gogantea(coll.et hemsl.)rehd.et wils for treating diarrhea. The active fraction in rose odorata sweet vat.gogantea(coll.et hemsl.)rehd.et wils for treating diarrhea mainly comprises tannin ingredients such as monomer catechin, gallic acid, dipolymer procyanidin B3 and the like as well as triterpene ingredients such as multinoside A, kajiichigoside F and the like. The active fraction has the advantages of enriched active ingredients, clear ingredients, stable content and definite curative effect, and has remarkable advantages on the aspect of treatment of diarrhea diseases.
A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2 mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking "phalanx" cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. I n hi biting P H D2 may offer alternative therapeutic opportunities for anti-cancer therapy, or other therapies where vascular normalization is beneficial.
The subjects will receive a single oral dose of midazolam 5 mg on Day 1. The subjects will receive darapladib 160 mg once daily on Days 3-14. The subjects will also receive a single dose of midazolam 5 mg on Day3 and 14.
Starting Day 22 of regimen A, Trastuzumab IV, Gemcitabine IV, and Cisplatin IV Day 1. Trastuzumab IV followed by Gemcitabine IV Day 8 and Trastuzumab IV Day 15. Repeats every 21 days for up to 5 courses.
Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient's survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.
1312675 Treating keratinous fibres SEPPIC 29 June 1970 [4 July 1969 10 July 1969 16 April 1970] 31446/70 Heading DIP A method of treating keratinous fibres which comprises applying to the fibres a solution or suspension containing at least one fluorinated compound of the formula R F -X-R in which R F  is a straight-chain or branched-chain alkyl radical having 5 to 18 C atoms and in which #50% of the H atoms have been replaced by fluorine atoms; X is a divalent ester amide or sulphonic radical, or an O atom and R is an alkyl or alkylene radical, and oxyalkylated chain, a mineral acid radical, an alkyl or carboxylic alkylene radical, a vinyl radical or a radical having the formula -(CH 2 ) m -Y-R 1  in which m is 1 to 12, Y is O, S or N atom and R, is an H atom or unsaturated radical; or a solution or suspension containing a homopolymer or copolymer of a compound of formula R F -X-R which contains a ethylenically unsaturated radical. The compound of formula (I) may be an ester of formula where n is 3 to 16. The homopolymers or copolymers of these unsaturated esters are products containing the unit The fluorinated compound may be an ester of an oxygenated mineral acid of formula R F -O -Z where R F  is a straight chain or branched chain alkyl radical having 5 to 18 C atoms in which #50% of the H atoms have been replaced by F atoms and Z is a metalloid such as sulphur, phosphorus or boron. The fluorinated compound may be a fatty acid amide of formula R F -CO-NR 2 -(CH 2 ) m -Y-R 1  in which R F  is a perfluorinated straight chain or branched chain alkyl or alkylene radical of 5 to 18 C atoms R 2  is a H atom or alkyl radical; m is an integer 1 to 12; Y is O, S or N atom and R 1  is a H atom or a radical bearing a polymerisable unsaturated radical, e.g. acrylic, methacrylic, vinylic or styrenic acid. The solution or suspension may also contain softeners and antistatic agents.
Accurate prediction of postoperative recurrence is important for optimizing the treatment strategies for non-small cell lung cancer (NSCLC). Previous studies identified the PD-L1 expression in NSCLC as a risk factor for postoperative recurrence. This study aimed to examine the contribution of PD-L1 expression to predicting postoperative recurrence using machine learning. The clinical data of 647 patients with NSCLC who underwent surgical resection were collected and stratified into training (80%), validation (10%), and testing (10%) datasets. Machine learning models were trained on the training data using clinical parameters including PD-L1 expression. The top-performing model was assessed on the test data using the SHAP analysis and partial dependence plots to quantify the contribution of the PD-L1 expression. Multivariate Cox proportional hazards model was used to validate the association between PD-L1 expression and postoperative recurrence. The random forest model demonstrated the highest predictive performance with the SHAP analysis, highlighting PD-L1 expression as an important feature, and the multivariate Cox analysis indicated a significant increase in the risk of postoperative recurrence with each increment in PD-L1 expression. These findings suggest that variations in PD-L1 expression may provide valuable information for clinical decision-making regarding lung cancer treatment strategies.
This study will test the Pain Relief Patch (PRP), a new device containing LEDs that is to be worn on the skin of the painful area, to see if it is effective in relieving chronic musculoskeletal back pain. It will also test the safety of the patch. The LEDs in the PRP emit a certain kind of light (peak wavelength 453 nm) that stimulates the production of nitric oxide (NO) in the skin. NO has been shown to induce a number of actions that should contribute to pain relief, including relaxation of smooth muscle cells, dilation of blood vessels, increased concentrations of oxygen in the cells and washout of metabolic byproducts and toxins caused by cell injury or death. Participants in one treatment group will be treated 5 times over 2 weeks for 30 minutes with PRP patches in the clinic. Participants in the control arm will be treated for the same length of time with a similar device that contains LEDs that emit another wavelength of light that does not induce production of NO. To prevent the influence of expectations on the results, neither the participants nor the medical staff directly responsible for their treatment will be told with which of the test patches the participants are treated. Other clinic staff will be responsible for all activities that could identify treatment arm, including putting the devices on and removing them, and examining the condition of the participants' skin before and after treatment. To get an accurate measure of how effective the devices are, participants will score their pain several times before the treatment period begins, as well as before and after each treatment. They will also complete several pain questionnaires during the study.
A device is described that can include a probe, a mobile device, and at least one processor. The probe can examine a corresponding anatomical part of a body. The mobile device can have a camera to take an image of the anatomical part of the body. The mobile device can execute a patient-application to process the image. The at least one processor can be configured to transmit the processed image to a server via a communication network. Related apparatuses, systems, methods, techniques and articles are also described.
The prone position has been used to treat severe hypoxemia in patients with acute respiration dysfunction syndrome (ARDS) since the 1970s, and it has significant effectiveness in improving gas exchange. Acute lung injury (ALI) is a common complication after congenital heart disease. The clinical manifestation is refractory hypoxemia. At present, mechanical ventilation is one of the main methods for the treatment of acute lung injury-induced respiratory distress syndrome. Prone position ventilation refers to placing the patient in the prone position during mechanical ventilation to expand the lungs in the atelectasis area and improve the ratio of lung ventilation and perfusion.

Prone position ventilation technology as an important lung protection ventilation strategy has been widely used clinically at home and abroad. Compared with adults, children are more convenient and easy to implement. Due to the exact mechanism of improving oxygenation function, the current domestic and foreign development of pediatric prone ventilation technology is mainly focused on children with ARDS. There are few studies on high-quality application effects after pediatric cardiac surgery, and almost no research has been carried out, especially for pediatric heart The indications for the implementation of the prone position after the disease surgery, the specific standardized process including the position angle, the prone duration plan, etc. all need to be studied. Therefore, there is an urgent need to develop prone position ventilation technology for critically ill children with congenital heart disease after surgery to reduce postoperative pulmonary complications and shorten the time of mechanical ventilation.
OBJECTIVE: Pressure wave reflection predicts cardiovascular events in the general population. Obesity is negatively associated with pressure wave reflection. Muscular arterial diameter (responsible for pressure wave reflection) increases with obesity, and obesity-dependent dilation of muscular arteries is attenuated in women compared with men. We investigated the sex differences in the cross-sectional relationship between obesity and pressure wave reflection in a general population cohort.
METHODS: Tonometric pressure waveforms were recorded in 928 adults (mean age, 56 ± 10 years) to estimate the aortic augmentation index. The BMI was calculated using height and body weight, and waist circumference was recorded at the umbilical level.
RESULTS: Aortic augmentation index was significantly higher in women than in men. Indices of obesity (BMI and waist circumference) were negatively correlated with the aortic augmentation index in both men and women, even after adjusting for mean arterial pressure (both P  < 0.001). Sex and BMI had no synergistic effect on the aortic augmentation index. However, when waist circumference was substituted for BMI, sex and waist circumference had a reciprocal influence on decreasing the aortic augmentation index independent of age, mean arterial pressure, diabetes, and hyperlipidemia (interaction, P  = 0.045).
CONCLUSION: The negative correlation between overweight/obesity and aortic pressure augmentation from peripheral wave reflection is inhibited in women more than in men. Sex differences in aortic pressure augmentation are greater in individuals with central (abdominal) obesity than in those with general obesity.
BACKGROUND: Gestational diabetes mellitus (GDM) has a strong genetic predisposition. Integrating metabolomics with Mendelian randomisation (MR) analysis offers a potent method to uncover the metabolic factors causally linked to GDM pathogenesis.
OBJECTIVES: This study aims to identify specific metabolites and metabolic pathways causally associated with GDM susceptibility through a comprehensive MR analysis. Additionally, it seeks to explore the potential of these identified metabolites as circulating biomarkers for early GDM detection and risk assessment. Furthermore, it aims to evaluate the implicated metabolic pathways as potential therapeutic targets for preventive or interventional strategies against GDM.
METHODS: A two-sample MR study was conducted using summary statistics from a metabolite genome-wide association study (GWAS) of 8299 individuals and a GDM GWAS comprising 13,039 cases and 197,831 controls. Rigorous criteria were applied to select robust genetic instruments for 850 metabolites.
RESULTS: MR analysis revealed 47 metabolites exhibiting putative causal associations with GDM risk. Among these, five metabolites demonstrated statistically significant associations after multiple-testing correction: Beta-citrylglutamate, Isobutyrylcarnitine (c4), 1,2-dilinoleoyl-GPC (18:2/18:2), Alliin and Cis-3,4-methyleneheptanoylcarnitine. Importantly, all these metabolites exhibited protective effects against GDM development. Additionally, metabolic pathway enrichment analysis implicated the methionine metabolism and spermidine and spermine biosynthesis pathways in the pathogenesis of GDM.
CONCLUSION: This comprehensive MR study has robustly identified specific metabolites and metabolic pathways with causal links to GDM susceptibility. These findings provide novel insights into the metabolic underpinnings of GDM aetiology and offer promising translational implications. The identified metabolites could serve as potential circulating biomarkers for early detection and risk stratification, while the implicated metabolic pathways may represent therapeutic targets for preventive or interventional strategies against GDM.
BACKGROUND: This study aimed to assess geometry changes of the ascending aorta after thoracic endovascular aortic repair (TEVAR) for descending aortic dissection and identify potential risk factors for diameter and length change.
METHODS: Between April 2009 and July 2021, 102 patients were treated for acute descending aortic dissections (type B and non-A non-B) with TEVAR and were included in this analysis. Computed tomography angiographic scans were transferred to a dedicated imaging software and detailed aortic measurements (including length, diameter and area) were taken in multiplanar reconstruction postoperatively, after 6 months and annually thereafter.
RESULTS: Sixty-five (58%) patients were male, with a mean age of 66 (±11). Four (4%) patients were diagnosed with connective tissue disease. Before TEVAR, 79% of our patients were treated with a mean of 1.5 (±1.2) different classes of antihypertensive medications. This number rose to 98% after TEVAR and 2.7 (±1.0) different antihypertensive drugs. There was no significant change in length, diameter, cross-sectional area, or volume of the ascending aorta during the follow-up of 3 years after TEVAR. Body height was a negative predictor for mean ascending aortic diameter (P value = -0.013; B = -8.890) and mean aortic diameter at the level of the brachiocephalic trunk (P value = 0.039; B = -14.763).
CONCLUSIONS: Our data suggest no significant changes in the ascending aorta following TEVAR of the descending thoracic aorta during mid-term follow-up when under stringent blood pressure medication. Additionally, we did not find any modifiable risk factors for geometry parameter increase.
Patients are allocated to this group at visit V1 if 10 mg/day escitalopram treatment resulted in optimal escitalopram exposure (25-50 ng/ml) as measured at VK. These patients will continue their treatment with 10 mg/day during the V1-V2 period.
BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components.
METHODS: In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.732 ≥ 3 months apart to define CKD. MRI scans were rated for ICH neuroimaging phenotype (arteriolosclerosis, cerebral amyloid angiopathy, mixed location SVD, or cryptogenic ICH) and the presence of markers of SVD (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces, defined according to the STandards for ReportIng Vascular changes on nEuroimaging criteria). We used multinomial, binomial logistic, and ordinal logistic regression models adjusted for age, sex, hypertension, and diabetes to account for possible confounding caused by shared risk factors of CKD and SVD.
RESULTS: Of 875 patients (mean age 66 years, 42% female), 146 (16.7%) had CKD. After adjusting for age, sex, and comorbidities, patients with CKD had higher rates of mixed SVD than those with eGFR >60 (relative risk ratio 2.39, 95% CI 1.16-4.94, p = 0.019). Severe WMHs, deep microbleeds, and lacunes were more frequent in patients with CKD, as was a higher overall SVD burden score (odds ratio 1.83 for each point on the ordinal scale, 95% CI 1.31-2.56, p < 0.001). Patients with eGFR ≤30 had more CMBs (median 7 [interquartile range 1-23] vs 2 [0-8] for those with eGFR >30, p = 0.007).
DISCUSSION: In patients with ICH, CKD was associated with SVD burden, a mixed SVD phenotype, and markers of arteriolosclerosis. Our findings indicate that CKD might independently contribute to the pathogenesis of arteriolosclerosis and mixed SVD, although we could not definitively account for the severity of shared risk factors. Longitudinal and experimental studies are, therefore, needed to investigate causal associations. Nevertheless, stroke clinicians should be aware of CKD as a potentially independent and modifiable risk factor of SVD.
Participants in the treatment condition start the online volunteer training immediately after randomization and completed the online module within 2-week. Then they are invited to attend the face-to-face training within 1-week. They will complete the post-intervention assessment right after they finish the face-to-face training, and be invited to participate in an interview.
The HPFS is an ongoing prospective study of 51,529 male health professionals (dentists, veterinarians, pharmacists, optometrists, osteopaths, and podiatrists) who were 40 to 75 years of age at enrollment in 1986. Approximately 97% of participants were of white European descent. Similar to the NHS cohorts, participants have been followed through mailed biennial questionnaires (https://www.hsph.harvard.edu/hpfs/hpfs-questionnaires/) that ascertained medical history, lifestyle, and health-related behaviors, as previously described.88,89 The 2004, 2006, and 2008 questionnaires included questions that elicited information on history of HZ and the year when the episode of HZ occurred. The upcoming 2024 questionnaire will also elicit information on history of HZ, whether participants had been vaccinated against HZ and the date of vaccination.
The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.