26,278 research outputs found

    Biomarkers in acute ischemic stroke

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    A systematic review to explore the effectiveness of physical health and psychosocial interventions on anxiety, depression and quality of life in people living with blood cancer

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    Problem identification. Anxiety and depression are more prevalent in hematological cancer patients who experience unpredictable illness trajectories and aggressive treatments compared to solid tumor patients. Efficacy of psychosocial interventions targeted at blood cancer patients is relatively unknown. This systematic review examined trials of physical health and psychosocial interventions intending to improve levels of anxiety, depression, and/or quality of life in adults with hematological cancers. Literature search. PubMed and CINAHL databases were used to perform a systematic review of literature using PRISMA guidelines. Data evaluation/synthesis. Twenty-nine randomized controlled trials of 3232 participants were included. Thirteen studies were physical therapy, nine psychological, five complementary, one nutritional and one spiritual therapy interventions. Improvements were found in all therapy types except nutritional therapy. Conclusions. Interventions that included personal contact with clinicians were more likely to be effective in improving mental health than those without. Implications for psychosocial oncology. Various psychosocial interventions can be offered but interactive components appear crucial for generating long-standing improvements in quality of life, anxiety and depression

    Comparison of Dense Net and over Logistic Regression in Predicting Leukemia Classification with Improved Accuracy

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    This study compares the performance of densenet and support vector machines (SVMs) in the diagnosis of leukemia disease, with the aim of improving the accuracy of the classification results. Materials and Method The Kaggle website is where the dataset was found. The dataset consists of 20 samples per group in JPG files with a resolution of 96 dpi and 512×512 pixel size.The sample size is determined using a pretest power of 80%, a threshold of 0.05, and a confidence interval of 95%. Results: For leukemia, dense net is 96.5%, whereas logistic regression is 89%. The significance levels for Densenet and logistic regression are data with p=.000 (p<0.05) statistical significance difference respectively. Conclusion: Based on the findings, I believe that densenet performs superior to logistic regression

    Immunoprecipitation methods impact the peptide repertoire in immunopeptidomics

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    IntroductionMass spectrometry-based immunopeptidomics is the only unbiased method to identify naturally presented HLA ligands, which is an indispensable prerequisite for characterizing novel tumor antigens for immunotherapeutic approaches. In recent years, improvements based on devices and methodology have been made to optimize sensitivity and throughput in immunopeptidomics. However, developments in ligand isolation, mass spectrometric analysis, and subsequent data processing can have a marked impact on the quality and quantity of immunopeptidomics data.MethodsIn this work, we compared the immunopeptidome composition in terms of peptide yields, spectra quality, hydrophobicity, retention time, and immunogenicity of two established immunoprecipitation methods (column-based and 96-well-based) using cell lines as well as primary solid and hematological tumor samples.ResultsAlthough, we identified comparable overall peptide yields, large proportions of method-exclusive peptides were detected with significantly higher hydrophobicity for the column-based method with potential implications for the identification of immunogenic tumor antigens. We showed that column preparation does not lose hydrophilic peptides in the hydrophilic washing step. In contrast, an additional 50% acetonitrile elution could partially regain lost hydrophobic peptides during 96-well preparation, suggesting a reduction of the bias towards the column-based method but not completely equalizing it.DiscussionTogether, this work showed how different immunoprecipitation methods and their adaptions can impact the peptide repertoire of immunopeptidomic analysis and therefore the identification of potential tumor-associated antigens

    Результаты ретроспективного исследования функциональных возможностей сердечно-сосудистой системы у больных хроническими лейкозами

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    Немногим более 20% случаев лейкоза в Северной Америке и Европе вызваны хроническим миелоидным лейкозом (ХМЛ), третьим по распространенности типом заболевания. А среди лейкозов заболеваемость ХМЛ занимает второе место в таких странах, как Япония и Индия. На каждые 100 000 человек во всем мире приходится примерно 1-1-15 случаев ХМЛ. Мужчины составляют от 55 до 60 процентов всех больных и болеют чаще, чем женщины. Пик заболеваемости приходится на возраст от 30 до 40 лет. Несмотря на то, что наследственный компонент ХМЛ до сих пор неизвестен, он был обнаружен в нескольких редких случаях. несколько членов семьи. В исследовании приняли участие 86 пациентов (20 из контрольной группы, 34 с хроническим лимфолейкозом (ХЛЛ) и 32 с хроническим миелоидным лейкозом (ХМЛ)). Для участия в программе пациенты должны быть в возрасте от 18 до 60 лет и иметь подтвержденный диагноз ХЛ. Пациенты с сопутствующими заболеваниями, клинически нестабильные, в исследование не включались. У каждого пациента оценивали клиническое состояние, вариабельность сердечного ритма и вегетативный тонус с помощью инструментальных методов диагностики, таких как эхокардиография, холтеровское мониторирование и электрокардиография (ЭКГ)

    Human granzyme B regulatory B cells prevent effector CD4+CD25- T cell proliferation through a mechanism dependent from lymphotoxin alpha

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    IntroductionHuman Granzyme B (GZMB) regulatory B cells (Bregs) have suppressive properties on CD4+ effector T cells by a mechanism partially dependent on GZMB. Moreover, these cells may be easily induced in vitro making them interesting for cell therapy.MethodsWe characterized this population of in vitro induced GZMB+Bregs using single cell transcriptomics. To investigate their regulatory properties, Bregs or total B cells were also co-cultured with T cells and scRNAseq was used to identify receptor ligand interactions and to reveal gene expression changes in the T cells.ResultsWe find that Bregs exhibit a unique set of 149 genes differentially expressed and which are implicated in proliferation, apoptosis, metabolism, and altered antigen presentation capacity consistent with their differentiated B cells profile. Notably, Bregs induced a strong inhibition of T cell genes associated to proliferation, activation, inflammation and apoptosis compared to total B cells. We identified and validated 5 receptor/ligand interactions between Bregs and T cells. Functional analysis using specific inhibitors was used to test their suppressive properties and we identified Lymphotoxin alpha (LTA) as a new and potent Breg ligand implicated in Breg suppressive properties.DiscussionWe report for the first time for a role of LTA in GZMB+Bregs as an enhancer of GZMB expression, and involved in the suppressive properties of GZMB+Bregs in human. The exact mechanism of LTA/GZMB function in this specific subset of Bregs remains to be determined

    The role of CD180 in hematological malignancies and inflammatory disorders.

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    Toll-like receptors play a significant role in the innate immune system and are also involved in the pathophysiology of many different diseases. Over the past 35 years, there have been a growing number of publications exploring the role of the orphan toll-like receptor, CD180. We therefore set out to provide a narrative review of the current evidence surrounding CD180 in both health and disease. We first explore the evidence surrounding the role of CD180 in physiology including its expression, function and signaling in antigen presenting cells (APCs) (dendritic cells, monocytes, and B cells). We particularly focus on the role of CD180 as a modulator of other TLRs including TLR2, TLR4, and TLR9. We then discuss the role of CD180 in inflammatory and autoimmune diseases, as well as in hematological malignancies of B cell origin, including chronic lymphocytic leukemia (CLL). Based on this evidence we produce a current model for CD180 in disease and explore the potential role for CD180 as both a prognostic biomarker and therapeutic target. Throughout, we highlight specific areas of research which should be addressed to further the understanding of CD180 biology and the translational potential of research into CD180 in various diseases

    Monoclonal antibodies binding to different epitopes of CD20 differentially sensitize DLBCL to different classes of chemotherapy

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    IntroductionRituximab (R), an anti-CD20 monoclonal antibody (mAb) and the world’s first approved antibody for oncology patients, was combined with the CHOP chemotherapy regimen and markedly improved the prognosis of all B- cell–derived lymphomas, the most common hematological malignancy worldwide. However, there is a 35% disease recurrence with no advancement in the first-line treatment since R was combined with the archetypal CHOP chemotherapy regimen nearly 30 years ago. There is evidence that R synergizes with chemotherapy, but the pharmacological interactions between R and CHOP or between newer anti-CD20 mAbs and CHOP remain largely unexplored.MethodsWe used in vitro models to score pharmacological interactions between R and CHOP across various lymphoma cell lines. We compared these pharmacological interactions to ofatumumab, a second-generation anti-CD20 mAb, and CHOP. Lastly, we used RNA-sequencing to characterize the transcriptional profiles induced by these two antibodies and potential molecular pathways that mediate their different effects.ResultsWe discovered vast heterogeneity in the pharmacological interactions between R and CHOP in a way not predicted by the current clinical classification. We then discovered that R and ofatumumab differentially synergize with the cytotoxic and cytostatic capabilities of CHOP in separate distinct subsets of B-cell lymphoma cell lines, thereby expanding favorable immunochemotherapy interactions across a greater range of cell lines beyond those induced by R-CHOP. Lastly, we discovered these two mAbs differentially modulate genes enriched in the JNK and p38 MAPK family, which regulates apoptosis and proliferation.DiscussionOur findings were completely unexpected because these mAbs were long considered to be biological and clinical equivalents but, in practice, may perform better than the other in a patient-specific manner. This finding may have immediate clinical significance because both immunochemotherapy combinations are already FDA-approved with no difference in toxicity across phase I, II, and III clinical trials. Therefore, this finding could inform a new precision medicine strategy to provide additional therapeutic benefit to patients with B-cell lymphoma using immunochemotherapy combinations that already meet the clinical standard of care
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