anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: The myocardium adapts to ischemia/reperfusion (I/R) by changes in gene expression, determining the cardiac response to reperfusion. mRNA translation is a key component of gene expression. It is largely unknown how regulation of mRNA translation contributes to cardiac gene expression and inflammation in response to reperfusion and whether it can be targeted to mitigate I/R injury.
METHODS: To examine translation and its impact on gene expression in response to I/R, we measured protein synthesis after reperfusion in vitro and in vivo. Underlying mechanisms of translational control were examined by pharmacological and genetic targeting of translation initiation in mice. Cell type-specific ribosome profiling was performed in mice that had been subjected to I/R to determine the impact of mRNA translation on the regulation of gene expression in cardiomyocytes. Translational regulation of inflammation was studied by quantification of immune cell infiltration, inflammatory gene expression, and cardiac function after short-term inhibition of translation initiation.
RESULTS: Reperfusion induced a rapid recovery of translational activity that exceeds baseline levels in the infarct and border zone and is mediated by translation initiation through the mTORC1 (mechanistic target of rapamycin complex 1)-4EBP1 (eIF4E-binding protein 1)-eIF (eukaryotic initiation factor) 4F axis. Cardiomyocyte-specific ribosome profiling identified that I/R increased translation of mRNA networks associated with cardiac inflammation and cell infiltration. Short-term inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory cytokines such as Ccl2 (C-C motif chemokine ligand 2) of border zone cardiomyocytes, thereby attenuating Ly6Chi monocyte infiltration and myocardial inflammation. In addition, we identified a systemic immunosuppressive effect of eIF4F translation inhibitors on circulating monocytes, directly inhibiting monocyte infiltration. Short-term pharmacological inhibition of eIF4F complex formation by 4EGI-1 or rapamycin attenuated translation, reduced infarct size, and improved cardiac function after myocardial infarction.
CONCLUSIONS: Global protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6Chi monocyte infiltration by inhibiting a proinflammatory response at the site of injury and of circulating monocytes.
Compositions and methods effective in inhibiting abnormal or undesirable cell proliferation, particularly endothelial cell proliferation and angiogenesis related to neovascularization and tumor growth are provided. The compositions comprise naturally occurring, or synthetic proteins, peptides, or protein fragments capable of binding to components of the blood coagulation pathway. The compositions may be administered using a pharmaceutically acceptable carrier. The methods involve administering to a human or animal the composition described herein in a dosage sufficient to inhibit cell proliferation, particularly endothelial cell proliferation. The methods are useful for treating diseases and processes mediated by undesired and uncontrolled cell proliferation, such as cancer, particularly by inhibiting angiogenesis. Administration of the composition to a human or animal having prevascularized metastasized tumors is useful for preventing the growth or expansion of such tumors.
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
Chronic idiopathic pruritus (CIP) is a frequent and disabling condition, with significative impact on quality of life. At present, there is no specific treatment for CIP. Topical steroids are frequently used, with partial efficacy, and adverse effects. Hypnosis is a specific state of conscience. It differs from waking state, sleeping state, relaxation, or meditation. In this state, the person is highly responsive to suggestion. In medicine, hypnosis can be used to engage the internal resources of the person against unpleasant feelings. It was shown previously that hypnosis can relieve painful sensations. Pain and pruritus share many similarities regarding sensory receptors and pathways, suggesting that hypnosis might help relief CIP.
INTRODUCTION: Pen-on-paper pain drawing are an easily administered self-reported measure that enables patients to report the spatial distribution of their pain. The digitalization of pain drawings has facilitated the extraction of quantitative metrics, such as pain extent and location. This study aimed to assess the reliability of pen-on-paper pain drawing analysis conducted by an automated pain-spot recognition algorithm using various scanning procedures.
METHODS: One hundred pain drawings, completed by patients experiencing somatic pain, were repeatedly scanned using diverse technologies and devices. Seven datasets were created, enabling reliability assessments including inter-device, inter-scanner, inter-mobile, inter-software, intra- and inter-operator. Subsequently, the automated pain-spot recognition algorithm estimated pain extent and location values for each digitized pain drawing. The relative reliability of pain extent analysis was determined using the intraclass correlation coefficient, while absolute reliability was evaluated through the standard error of measurement and minimum detectable change. The reliability of pain location analysis was computed using the Jaccard similarity index.
RESULTS: The reliability analysis of pain extent consistently yielded intraclass correlation coefficient values above 0.90 for all scanning procedures, with standard error of measurement ranging from 0.03% to 0.13% and minimum detectable change from 0.08% to 0.38%. The mean Jaccard index scores across all dataset comparisons exceeded 0.90.
CONCLUSIONS: The analysis of pen-on-paper pain drawings demonstrated excellent reliability, suggesting that the automated pain-spot recognition algorithm is unaffected by scanning procedures. These findings support the algorithm's applicability in both research and clinical practice.
FIELD: hygiene.SUBSTANCE: group of inventions relates to an oral care composition with high water content and a method for use thereof. Disclosed is an oral care composition containing at least 45 wt. % water in a total composition; at least 20 wt. % by weight of composition of 70 % sorbitol solution by weight of the composition; system for thickening, which is a combination of carboxymethyl cellulose and xanthan. Carboxymethyl cellulose is present in the composition in amount of 0.60 wt. % by weight of the composition and xanthan is present in the composition in an amount of about 0.65 wt. % by weight of the composition. Composition does not contain glycerol, water-soluble ions of bivalent tin and additional preserving agents. Disclosed also is a method for cleaning a dental surface, involving use of said composition.EFFECT: use of said quantitative sorbitol content in the presence of a combination of carboxymethyl cellulose and xanthan provides a microorganism protection index of at least 0,75 in an oral care composition with a high water content without using any additional preserving agents.11 cl, 2 tbl, 6 ex
BACKGROUND: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined.
METHODS: We sequenced and analyzed the genomes of families with diverse phenotypes who were suspected to have a rare monogenic disease and for whom genetic testing had not revealed a diagnosis, as well as the genomes of a replication cohort at an independent clinical center.
RESULTS: We sequenced the genomes of 822 families (744 in the initial cohort and 78 in the replication cohort) and made a molecular diagnosis in 218 of 744 families (29.3%). Of the 218 families, 61 (28.0%) - 8.2% of families in the initial cohort - had variants that required genome sequencing for identification, including coding variants, intronic variants, small structural variants, copy-neutral inversions, complex rearrangements, and tandem repeat expansions. Most families in which a molecular diagnosis was made after previous nondiagnostic exome sequencing (63.5%) had variants that could be detected by reanalysis of the exome-sequence data (53.4%) or by additional analytic methods, such as copy-number variant calling, to exome-sequence data (10.8%). We obtained similar results in the replication cohort: in 33% of the families in which a molecular diagnosis was made, or 8% of the cohort, genome sequencing was required, which showed the applicability of these findings to both research and clinical environments.
CONCLUSIONS: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.).
BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.
METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure.
RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity.
CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).
To construct and internally and externally validate a nomogram model for predicting the severity of acute pancreatitis (AP) based on the CT severity index (CTSI).A retrospective analysis of clinical data from 200 AP patients diagnosed at the Hefei Third Clinical College of Anhui Medical University from June 2019 to June 2022 was conducted. Patients were classified into non-severe acute pancreatitis (NSAP, n = 135) and severe acute pancreatitis (SAP, n = 65) based on final clinical diagnosis. Differences in CTSI, general clinical features, and laboratory indicators between the two groups were compared. The LASSO regression model was used to select variables that might affect the severity of AP, and these variables were analyzed using multivariate logistic regression. A nomogram model was constructed using R software, and its AUC value was calculated. The accuracy and practicality of the model were evaluated using calibration curves, Hosmer-Lemeshow test, and decision curve analysis (DCA), with internal validation performed using the bootstrap method. Finally, 60 AP patients treated in the same hospital from July 2022 to December 2023 were selected for external validation.LASSO regression identified CTSI, BUN, D-D, NLR, and Ascites as five predictive factors. Unconditional binary logistic regression analysis showed that CTSI (OR = 2.141, 95%CI:1.369-3.504), BUN (OR = 1.378, 95%CI:1.026-1.959), NLR (OR = 1.370, 95%CI:1.016-1.906), D-D (OR = 1.500, 95%CI:1.112-2.110), and Ascites (OR = 5.517, 95%CI:1.217-2.993) were independent factors influencing SAP. The established prediction model had a C-index of 0.962, indicating high accuracy. Calibration curves demonstrated good consistency between predicted survival rates and actual survival rates. The C-indexes for internal and external validation were 0.935 and 0.901, respectively, with calibration curves close to the ideal line.The model based on CTSI and clinical indicators can effectively predict the severity of AP, providing a scientific basis for clinical decision-making by physicians.
The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.
AIMS: We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress.
METHODS AND RESULTS: NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed. CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet.
CONCLUSION: Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.
The non-compressive bioactive garment is a commercially available garment that is designed to reflect infrared waves generated by the wearer back into the soft tissue surrounded by the garment. The reflection of the infrared waves is intended to improve pain and swelling at the site. Patients following Total knee replacement are intended to wear morning and night for the first 2 weeks post-operatively, and then as tolerated for 4 weeks afterwards. The patients will then discontinue use of the sleeve after 6 weeks.
The present invention relates to external application medicine for burns and scalds, which is characterized in that the present invention is composed of the following medicine: 5 to 20 g of rhubarb powder, 5 to 20 g of garden burnet root powder, 5 to 20 g of imperatae rhizoma powder, 10 to 30 g of tonggen powder, 5 to 20 g of borneol powder and 150 to 300 g of VB6 powder. The present invention can be made into oil solution or paste according to needs. The preparation process of the oil solution comprises the steps: 80 to 120 g of sesame oil is placed in a sterilizer and is boiled for 30 to 40 minutes or is sterilized with a microwave sterilization method; then, the medicine after sterilization is put in the cooled sesame oil to make the oil solution. The preparation process of the paste comprises the steps: 10 to 20 g of vaseline is added to the medicine after sterilization, and the mixture is stirred into the paste. The combination way of traditional Chinese medicine and western medicine is used in the present invention. The present invention has the advantages of a few components, short treatment time, no scars left after cure, no pains for patients, simple preparation process, low cost and easy realization. The present invention not only has good curative effects on various burns, but also has a certain cure effect on other skin wounds.
Newborn screening (NBS) by testing dried blood spots (DBS) identifies newborns with a few diseases for which effective treatments are available to enable treatment at or before symptom onset. Because NBS improves outcomes in these diseases, it is performed on almost all US babies. The current Federal recommended NBS list is limited to 35 conditions and identifies \~6,600 affected children per year. In genetic diseases not screened by NBS, however, outcomes remain poor because of delays in diagnosis and treatment. The investigators recently developed a system for NBS for 434 severe, childhood genetic diseases for which effective treatments are available using whole genome sequencing (WGS), called BeginNGS. Retrospective studies showed BeginNGS to have a true negative rate (specificity) of 99.7% and true positive rate (sensitivity) of 88.8%. The investigators now propose to undertake a first prospective study in newborns admitted to the Neonatal Intensive Care Unit (NICU) at Rady Children's Hospital, San Diego (RCHSD) to compare the sensitivity and specificity of BeginNGS with that of standard, diagnostic rapid whole genome sequencing (DWGS) and whole exome sequencing (WES). This study is in preparation for larger, future clinical trials.
This disclosure describes, in one aspect, a composition that generally includes a hydrophobic biologically active material and an emulsifier coating at least a portion of the hydrophobic biologically active material. In some embodiments, the hydrophobic biologically active material can include an amino acid or a combination of amino acids. In certain embodiments, the amino acids can be leucine, isoleucine, valine, or any combination of two or more of those amino acids. In another aspect, this disclosure describes a composition comprising a liquid and an emulsifier-coated hydrophobic biologically active material. In some embodiments, after the liquid and the emulsifier-coated hydrophobic biologically active material are mixed, the resulting composition transmits at more than 50% of light at 520 nm. In some embodiments, after the liquid and the emulsifier-coated hydrophobic biologically active material are mixed, at least 67% of the emulsifier-coated hydrophobic biologically active material is sufficiently dissolved or dispersed to pass through a 20 μm filter.
In addition to events reported in clinical trials, the following events have been identified during use of LOTRONEX in clinical practice. Because they were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to LOTRONEX. 

     Gastrointestinal: Impaction, perforation, ulceration, small bowel mesenteric ischemia. 
     Neurological: Headache. 
     Skin: Rash.
The invention discloses an external medicine used for treating tinea cruris, and a preparation method thereof. The invention belongs to the field of traditional Chinese medicine preparation. The medicine provided by the invention is prepared from raw materials of, by weight: 60 to 80 parts of slender dutchmanspipe root, 20 to 50 parts of sessile stemona root tuber, 10 to 20 parts of lightyellow sophora root, 20 to 60 parts of belvedere fruit, 10 to 30 parts of amur corktree bark, 10 to 20 parts of argy wormwood leaf, 5 to 10 parts of fructus zanthoxyli, 20 to 40 parts of coptis root, 40 to 80 parts of dried alum, and 12 to 14 parts of borneol. Preferably, the medicine is prepared from raw materials of, by weight: 60 parts of slender dutchmanspipe root, 30 parts of sessile stemona root tuber, 10 parts of lightyellow sophora root, 30 parts of belvedere fruit, 10 parts of amur corktree bark, 10 parts of argy wormwood leaf, 6 parts of fructus zanthoxyli, 20 parts of coptis root, 40 parts of dried alum, and 12 parts of borneol. According to the invention, slender dutchmanspipe root, sessile stemona root tuber, lightyellow sophora root, belvedere fruit, amur corktree bark, argy wormwood leaf, fructus zanthoxyli, and coptis root are cleaned, and are added to water according to the weight ratio; the mixture is decocted, and a juice is obtained; dried alum and borneol are forged with the juice; and the mixture is cooled and grinded into powder. The medicine is advantaged in that: compared to other external medicines, the treatment effect of the medicine provided by the invention is substantial; with the medicine, a patient can be completely and radically cured from tinea cruris.