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It is known that some mutant peptides, such as those resulting from missense mutations and frameshift insertions, can bind to the major histocompatibility complex and be presented to antitumor T cells on the surface of a tumor cell. These peptides are termed neoantigen, and it is important to understand this process for cancer immunotherapy. Here, we introduce an R package termed Neoantimon that can predict a list of potential neoantigens from a variety of mutations, which include not only somatic point mutations but insertions, deletions and structural variants. Beyond the existing applications, Neoantimon is capable of attaching and reflecting several additional information, e.g. wild-type binding capability, allele specific RNA expression levels, single nucleotide polymorphism information and combinations of mutations to filter out infeasible peptides as neoantigen.
The R package is available at http//github/hase62/Neoantimon.
The R package is available at http//github/hase62/Neoantimon.In the Czech Republic, the program managing high radon levels in dwellings has existed for nearly 30 years. Although the recent history of radiation protection from naturally radioactive gas is quite well known, prior radon management is less understood. This article describes the history of natural radioactivity and its management from the Middle Ages, showing that Czech countries have a much longer and abundant history related to natural radioactivity.
The protein kinase ATM (ataxia telangiectasia mutated) mediates cellular response to DNA damage induced by radiation. ATM inhibition decreases DNA damage repair in tumor cells and affects tumor growth. AZD1390 is a novel, highly potent, selective ATM inhibitor designed to cross the blood-brain barrier (BBB) and currently evaluated with radiotherapy in a Phase 1 study in patients with brain malignancies. In the present study, PET was used to measure brain exposure of 11C-labelled AZD1390 after intravenous (i.v.) bolus administration in healthy subjects with an intact BBB.
AZD1390 was radiolabeled with carbon-11 and a microdose (mean injected mass 1.21µg) was injected in 8 male subjects (21-65 years). The radioactivity concentration of [ 11C]AZD1390 in brain was measured using a high-resolution PET system. Radioactivity in arterial blood was measured to obtain a metabolite corrected arterial input function for quantitative image analysis. Participants were monitored by laboratory examinations, vital signs, udies.
Immune dysregulation contributes to the development of RA. Altered surface expression patterns of integrin adhesion receptors by immune cells is one mechanism by which this may occur. We investigated the role of β2 integrin subunits CD11a and CD11b in dendritic cell (DC) subsets of RA patients.
Total β2 integrin subunit expression and its conformation ('active' vs 'inactive' state) were quantified in DC subsets from peripheral blood (PB) and SF of RA patients as well as PB from healthy controls. Ex vivo stimulation of PB DC subsets and in vitro-generated mature and tolerogenic monocyte-derived DCs (moDCs) were utilized to model the clinical findings. Integrin subunit contribution to DC function was tested by analysing clustering and adhesion, and in co-cultures to assess T cell activation.
A significant reduction in total and active CD11a expression in DCs in RA SF compared with PB and, conversely, a significant increase in CD11b expression was found. These findings were modelled in vitro using moDCs tolerogenic moDCs showed higher expression of active CD11a and reduced levels of active CD11b compared with mature moDCs. Finally, blockade of CD11b impaired T cell activation in DC-T cell co-cultures.
For the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.
For the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.This case study provides a view of the behavior of radon in an uninhabited house, the likes of which were built in thousands in Slovakia between 1950 and 1990. In one room of the house that was in contact with the subsoil, an average annual radon activity concentration (RAC) as high as 1088 Bq m-3 was found. A high radon supply to this room from the subsoil was identified in the corner of the room, and this correlated very well with the temperature difference between indoor and outdoor air. In this room, an atypical annual variation of RAC was found, with a maximum in September (1600 Bq m-3). In the other rooms on the ground floor, RACs at the level of 400-500 Bq m-3 were detected. In the rooms on the first floor, RACs of up to ~200 Bq m-3 were found.This article focuses on an experimental study of the influence of imperfections on the value of the radon diffusion coefficient of various waterproofing materials. Microscopic holes were made by a thin tip or by a microdrill bit to imitate the real damage that can be incurred during construction. To determine the change in the radon diffusion coefficient, each waterproofing material was measured five times. The first measurement was performed on undamaged samples, while the following measurements were performed on samples with one, two, four and eight pinholes. The radon diffusion coefficient was measured under nonstationary conditions, because homemade radon sources with a slow rate of radon emanation were used. The radon diffusion coefficients identified in the study were compared according to the thickness of the material and the number and the size of the pinholes. The exact shape and size of the imperfections were documented by an electron microscope.The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). SGI-1027 cell line This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.
To evaluate the impact of the routine use of musculoskeletal ultrasound (MSUS) in rheumatology clinics by comparing one clinic with on-site MSUS (REU 1) and four clinics without this resource, which need to refer patients for the MSUS exams (REU 2-5).
The electronic medical records of all new patients at five rheumatology clinics during a 12-month period were reviewed. The impact of MSUS was analysed by comparing the percentage of direct discharges of patients from the different clinics, as an outcome of effectiveness, and the number and cost of radiology referrals for imaging exams (MSUS and MRI), as an outcome of cost-saving.
The medical records of 4923 patients were included in the study, distributed as follows REU 1, 1464 (29.7%); REU 2, 1042 (21.2%); REU 3, 1089 (22.1%); REU 4, 579 (11.8%); and REU 5, 749 (15.2%). There were more direct discharges from REU 1 (34.4%) than from REU 2-5 (15.6%) (P<0.001). REU 1 made radiological referrals for X-rays, MRIs or MSUS exams in 773 (52.8%) patients, compared with 2626 (75.9%) patients in REU 2-5 (P<0.001). An estimation of costs for the clinical assessment of 1000 new patients revealed a cost-saving in REU 1 of €21413 in MSUS and of €877 in MRI exams.
The implementation of on-site MSUS in a new-patient rheumatology clinic is cost-effective, facilitating the direct discharge of patients and reducing the number and cost of radiological referrals for imaging exams.
The implementation of on-site MSUS in a new-patient rheumatology clinic is cost-effective, facilitating the direct discharge of patients and reducing the number and cost of radiological referrals for imaging exams.
To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS).
Prospective, open-label, single-arm pilot study.
University hospital.
Seventeen patients with diagnosed BMS were included.
Subjects were treated for 4 weeks with a full cannabis plant extract, which was prepared from standardized plant material (cannabis flos) in specialized pharmacies by means of Romano-Hazekamp extraction and was diluted in oil (1 g of cannabis in 10 g of olive oil). The primary outcome was the change in pain intensity (assessed by the visual analog scale, Present Pain Intensity scale, McGill Pain Questionnaire, and Oral Health Impact Profiles) at the end of the protocol and during the succeeding 24 weeks; the neuropathic pain was also investigated with a specific interview questionnaire (DN4-interview [Douleur Neuropathique en 4 Questions]). Levels of anxiety and depression were considered as secondary outcomes, together with reported adverse events due to the specified treatment.
Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events.
In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.
In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.
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